Raphael JH, ed. Cancer Pain Management. British Pain Society 2010. ISBN:978-0-9551546-7-6

Full text

Cancer Pain Management
A perspective from the British Pain Society, supported by the
Association for Palliative Medicine and the Royal College of
General Practitioners
The British Pain Society's
January 2010
To be reviewed January 2013

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Published by:
The British Pain Society
3rd oor
Churchill House
35 Red Lion Square
London WC1R 4SG
Website: www.britishpainsociety.org
ISBN: 978-0-9551546-7-6
© The British Pain Society 2010

Contents
Page
Preface 5
Executive Summary 7
Chapter 1 Introduction 9
Chapter 2 Pathophysiology of cancer pain and opioid tolerance 15
Chapter 3 Cancer pain assessment 25
Chapter 4 Oncological management of cancer pain 31
Chapter 5 Modern pharmacological management of cancer pain 41
Chapter 6 Psychological aspects and approaches to pain management in cancer survivors 49
Chapter 7 Physical therapies for cancer pain 55
Chapter 8 Invasive procedures for cancer pain 63
Chapter 9 Complementary therapies for cancer pain 73
Chapter 10 Cancer pain management in the community 77
Chapter 11 Pain related to cancer treatments 85
Chapter 12 Management of acute pain in cancer patients 91
Chapter 13 Complex problems in cancer pain 95
Chapter 14 Cancer pain recommendations for service design and training 107
Membership of group and expert contributors 110
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Preface
This discussion document about the management of cancer pain is written from the pain specialists’ perspective
in order to provoke thought and interest through a multimodal approach to the management of cancer pain, and
not just towards the end of life, but also pain at diagnosis, as a consequence of cancer therapies and in cancer
survivors. The document relates the science of pain to the clinical setting and explains the role of psychological,
physical, interventional and complementary therapies in cancer pain.
It is directed at physicians and other healthcare professionals who treat pain from cancer at any stage of the
disease with the hope of raising awareness of the types of therapies that may be appropriate and increasing
awareness of the role of the pain specialist in cancer pain management, which can lead to greater dialogue and
liaison between oncology, specialist pain and palliative care professionals.
The document is accompanied by information for patients that can help them and their carers understand the
available techniques and that will support treatment choices.
Methods
This document has been produced by a consensus group of relevant healthcare professionals and patients’
representatives, making reference to the current body of evidence relating to cancer pain.
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Executive summary
• It is recognised that the World Health Organisation (WHO) analgesic ladder, whilst providing relief of
cancer pain towards the end of life for many suerers worldwide, may have limitations in the context of
long-term survival and increasing disease complexity. In order to address these weaknesses, it is suggested
that a more comprehensive model of cancer pain management is needed that is mechanism-based and
multimodal, using combination therapies including interventions where appropriate, which is tailored to
the needs of an individual, with the aim of optimising pain relief while minimalising adverse eects.
• The neurophysiology of cancer pain is complex: it involves inammatory, neuropathic, ischaemic and
compression mechanisms at multiple sites. A knowledge of these mechanisms and the ability to decide
whether a pain is nociceptive, neuropathic, visceral or a combination of all three will lead to best practice
in pain management.
• People with cancer can report the presence of several dierent anatomical sites of pain, which may be
caused by the cancer, by treatment of cancer, by general debility or by concurrent disorders. Accurate
and meaningful assessment and reassessment of pain is essential and optimises pain relief. History,
examination, psychosocial assessment and accurate record keeping should be routine, with pain and
quality of life measurement tools used where appropriate.
• Radiotherapy, chemotherapy, hormones, bisphosphonates and surgery are all used to treat and palliate
cancers. Combining these treatments with pharmacological and non-pharmocological methods of pain
control can optimise pain relief, but the limitations of these treatments must also be acknowledged.
• Opioids remain the mainstay of cancer pain management, but the long-term consequences of
tolerance, dependency, hyperalgesia and the suppression of the hypothalamic/pituitary axis should be
acknowledged and managed in both non-cancer and cancer pain, in addition to the well-known side-
eects such as constipation. NSAIDs, antiepileptic drugs, tricyclic antidepressants, NMDA antagonists,
sodium channel blockers, topical agents and the neuraxial route of drug administration all have their place
in the management of complex cancer pain.
• Psychological distress increases with the intensity of cancer pain. Cancer pain is often under-reported
and under-treated for a variety of complex reasons, partly due to a number of beliefs held by patients,
families and healthcare professionals. There is evidence that cognitive behavioural techniques that
address catastrophising and promote self-ecacy lead to improved pain management. Group format pain
management programmes could contribute to the care of cancer survivors with persistent pain.
• Physiotherapists and Occupational Therapists have an important role in the management of cancer pain
and have specic skills which enable them to be both patient-focused and holistic. Therapists utilise
strategies which aim to improve patient functioning and quality of life, but the challenge remains for them
to practice in an evidence-based way and more research is urgently needed in this eld.
• Patient selection for an interventional procedure requires knowledge of the disease process, the prognosis,
the expectations of patient and family, careful assessment and discussion with the referring physicians.
There is good evidence for the eectiveness of coeliac plexus neurolysis and intrathecal drug delivery.
Despite the limitations of running randomised controlled trials for interventional procedures in patients
with limited life expectancy and severe pain, there is a body of evidence of data built up over many
years that supports an important role for some procedures, such as cordotomy. Safety, aftercare and the
management of possible complications have to be considered in the decision making process. Where
applied appropriately and carefully at the right time, these procedures can contribute enhanced pain relief,
reduction of medication use and markedly improved quality of life.
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• There is a weak evidence base for the eectiveness of complementary therapies in terms of pain control,
but they may improve wellbeing. Safety issues are also a consideration in this area.
• Patients with cancer pain spend most of their time in the community until their last month of life. Older
patients and those in care homes in particular may have under-treated pain. Primary care teams supported
by palliative care teams are best placed to initiate and manage cancer pain therapy, but education of
patients, carers and healthcare professionals is essential to improve outcomes.
• Surgery, chemotherapy and radiotherapy are cancer treatments that can cause persistent pain in cancer
survivors, up to 50% of whom may experience persistent pain that adversely aects their quality of life.
Awareness of this problem may lead to preventative strategies, but treatment is currently symptom based
and often inadequate.
• Management of acute pain, especially post-operative pain, in patients on high dose opioids is a challenge
that requires in-depth knowledge of pharmacokinetics and the formulation of a careful management plan
to avoid withdrawal symptoms and inadequate pain management.
• Chronic pain after cancer surgery may occur in up to 50% of patients. Risk factors for the development of
chronic pain after breast cancer surgery include: young age, chemo and radiotherapy, poor post-operative
pain control and certain surgical factors. Radiotherapy induced neuropathic pain has become less
prevalent, but can cause long-standing pain and disability.
• Patient education is an eective strategy to reduce pain intensity.
• Cancer pain is often very complex, but the most intractable pain is often neuropathic in origin, arising
from tumour invasion of the meninges, spinal cord and dura, nerve roots, plexuses and peripheral nerves.
Multimodal therapies are necessary.
• The management of cancer pain can and should be improved by better collaboration between the
disciplines of oncology, pain medicine and palliative medicine. This must start in the training programmes
of doctors, but is also needed in established teams in terms of funding, time for joint working and the
education of all healthcare professionals involved in the treatment of cancer pain.
• The principles of pain management and palliative care for adult practice are relevant to paediatrics, but the
adult model cannot be applied directly to children.

Chapter 1 Introduction
Summary
It is recognised that the WHO analgesic ladder, whilst providing relief of cancer pain towards the end of life for
many suerers, may have limitations in the context of long-term survival and increasing disease complexity in
many countries.
It is suggested that a new model of cancer pain management is needed that is mechanism-based and
multimodal, using combination therapies including interventions where appropriate, which is tailored to the
needs of an individual, with the aim of optimising pain relief while minimalising adverse eects.
1.1 Focus and Purpose
The focus of this discussion document is on the patient with cancer pain.
The purpose of this document is:
• To highlight the importance of recognising cancer related pain and to optimise management.
• To acknowledge the achievements and successes of modern multiprofessional pain treatments for
cancer patients.
• To highlight areas of continuing poor achievement and gaps in services.
• To emphasise pain management for the cancer population with evidence based multimodal and
mechanism-based treatments.
• To strengthen the relationship between Palliative Care, Oncology and Pain Medicine.
1.2 Approach to cancer pain management
The optimal control of chronic pain in cancer relies on an understanding of the underlying pathophysiology and
molecular mechanisms involved, examples being:
• Direct tumour invasion of local tissues.
• Metastatic bone pain.
• Osteoporotic bone and degenerative joint pain in older people.
• Visceral obstruction.
• Nerve compression and plexus invasion.
• Ischaemia.
• Inammatory pain.
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• Chemotherapy induced neuropathy, paraneoplastic neuropathy and arthropathy.
• Post-surgical pain and radionecrosis.
Management thus starts with the diagnosis of the cause of pain by clinical assessment and imaging.
The ideal mode of palliation (symptom control) is the removal or minimisation of the cause (i.e. disease-directed
therapies). For example, in malignant bone pain, surgery, chemotherapy, radiotherapy and/or bisphosphonates
may be used. For an infection, antimicrobials or surgical drainage of an abscess may be required.
Alongside disease directed therapy, there are a host of pharmacological and non-pharmacological therapies,
which should be used on an individual basis depending on the specic clinical situation. Cancer pain
management remains an area where, in selected dicult cases, destructive neurosurgical procedures can be
appropriate because the limited life expectancy minimises the risk of secondary deaerentation pain.
1.3 Need for better cancer pain management
Previous data has shown the need for better cancer pain management. UK Cancer Deaths numbered 153,397 in
2004 (UK National audit Oce reports 2000, 2004). A conservative estimate has suggested that 10% fail to receive
eective relief by WHO guidelines; however, this is an underestimation given recent surveys (EPIC 2007, Valeberg,
2008) which show that, in reality, upwards of 30% of patients receive poor pain control, especially in the last year
of their lives.. Thirty percent represents 46,020 patients “failing per year”. If we add in the gures for troublesome
side-eects, then the present situation is even worse.
This is a higher percentage of uncontrolled pain than has previously been recognized. There is a variety of possible
explanations, including complexity of conditions, better surveys, simple cases being treated within primary care -
with more complex cases therefore being treated within specialised units - and compliance with treatments.
1.4 Role of pain service techniques
Several publications support the role of pain service techniques in cancer pain management (DH, 2002; SIGN,
2000; NICE, 2004).
Previous data has shown how pain services can contribute to better cancer pain management. In the Grampian
survey (Linklater, 2002), regular weekly joint sessions with pain management contributed usefully in 11% of total
cases, with interventions such as nerve blocks performed in 8% of cases. Formal collaboration between palliative
care and pain services have resulted in increased service activity (Kay, 2007).
1.5 Unmet needs
Despite recommendations and the demonstration of patients’ needs, these needs are not being met. The trend
over the past two decades towards excluding pain specialists from mainstream cancer pain management means
that they tend to be called in at a very late stage as a ‘last resort’. Patients may be missing out on the benets of
combined multidisciplinary care combining palliative care and pain medicine.
There is evidence of under-referral and that referral structures are patchy. Pain clinics are not resourced to respond
to needs and the availability of interventions is limited.

There appears to be a lack of engagement with organisational structures such as cancer networks and a lack
of lead intervention as recommended. There is a need to focus on a multidisciplinary approach to cancer pain
management, and training must reect this.
1.6 Working models
The WHO analgesic ladder, which has the clear principle of regular “by the clock” oral medication, has helped
cancer suerers all round the world in a cost-eective manner. However, the increasing complexity of cancer and
its treatment in the developed world has led to a dawning realisation of the limitations of the stepped analgesia
approach. There is a need for dierent working models that recognise the limitations of the WHO ladder (Hanks,
2001; Wien, 2007).
Pain management should not only be considered after all oncological treatments have been exhausted, but
should begin much earlier at pre-diagnosis (NICE, 2004), when pain is often a patient’s presenting symptom.
During a patient’s journey, there will be a need for pain management as a result of cancer treatments (Chapters
11,12) and the development of metastatic disease (chapter 4), in addition to the management of pain at the end
of life. Increasingly, cancer patients are going into remission with an increasing length of survival, but they do
suer from persistent pain (chapter 6) (Ahmedzai, 2000). The importance of holistic care and support throughout
this journey should be acknowledged (Ahmedzai, 2001).
In the treatment of bone pain, the second step on the WHO analgesic ladder is commonly unhelpful, with
inadequate pain relief or the development of undesirable/intolerable side-eects (Eisenberg, 2005). There is
currently no place for interventional treatment on the ladder and the earlier recommendations of a fourth step of
interventional management are not applied widely enough.
The main principles of pain management, including the use of a biopsychosocial approach, should be applied,
rather than simply following the WHO ladder.
Mechanism-based strategies incorporating the recent scientic discoveries of the molecular and cellular changes
in chronic and cancer pain are important. For example, treating bone metastases with bisphosphonates,
neuropathic pain with NMDA antagonists and the use of palliative chemotherapy with biological treatments,
radiation therapy and radioactive isotopes.
There is value in minimally invasive investigations for ‘dicult’ pains, such as bone scans, MRI, CT and
electrophysiological testing. There is a need for clear information on what pain services can provide and how they
may be accessed. Better links between palliative care and specialist pain services are also important.
Care of a patient suering from cancer pain requires a holistic approach combining psychological support, social
support, rehabilitation and pain management in order to provide the best possible quality of life or quality of
death. The WHO 3-step analgesic ladder model has made an enormous contribution, but does have limitations: it
has never been validated and morphine is arguably not the “gold standard”, but rather a standard; non-oral routes
may be better and preferable at times.
It is time to move towards a new model of cancer pain management which is mechanism-based, multimodal,
uses combination therapies, is interventional where justied and advocates personalised medicine with the aim
of optimising pain relief while minimalising adverse eects.
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Figure 1
Figure 2
Sheffield model of supportive care
Treating the cancer, patient and family
Adapted from: Ahmedzai, Walsh
Adapted from: Ahmedzai, Walsh Seminars in Oncol
Seminars in Oncol 2000
2000
Diagnosis
Diagnosis
Screening
Screening
Investigation
Investigation
Grief / Bereavement
Grief / Bereavement
Disease-directed therapy
Disease-directed therapy
Patient-directed therapy
Patient-directed therapy
Family-directed therapy
Family-directed therapy
Death
Death
Remission-----Cure-----Relapse
Remission-----Cure-----Relapse
Co-morbidity – Information -- Side-effects --- Rehabilitation
Co-morbidity – Information -- Side-effects --- Rehabilitation
Information --- Psychological support --- Financial help
Information --- Psychological support --- Financial help
Survivorship
Supportive Care

References
Ahmedzai SH. Window of opportunity for pain control in the terminally ill. Lancet 2000;357:9265.1304-1305.
Ahmedzai SH, Walsh TD. Palliative medicine and modern cancer care. Seminars Oncology 2001;27:1-6.
DH, Specialised Services National Denition Set 31. Specialised pain management services (adult). Published:
19/12/2002.
Eisenberg. Pain Clinical Updates (2005). Vol X111,(5).
European Pain in Cancer (EPIC) survey (2007). Cited in www.EPICsurvey.com.
Hanks GW, de Conno F, Cherny N, Hanna M, Kalso E, McQuay HJ Mercadante S, Meynadier J, Poulain P, Ripamonti
C, Radbruch L, Casas JR, Sawe J, Twycross RG, Ventafridda V. Morphine and alternative opioids in cancer pain: the
EAPC recommendations. Expert Working Group of the Research Network of the European Association for Palliative
Care. British Journal of Cancer 2001;84:587- 593.
Kay S, Husbands E, Antrobus JH, Munday D. Provision for advanced pain management techniques in adult
palliative care: a national survey of anaesthetic pain specialists. Palliative Medicine 2007;21(4):279-284.
Linklater GT, Leng MEF, Tiernan EJJ, Lee MA, Chambers WA. Pain management services in palliative care: a national
survey. Palliative Medicine 2002;16:435-439.
National Audit Oce Report. The NHS cancer plan: a plan for investment, a plan for reform. Department of Health
2000.
National Audit Oce Report. Tackling cancer: improving the patient journey. Session 2004-5. HC 288. 24 Feb 2005.
NICE Guidance on cancer services. Improving supportive and palliative care for adults with cancer. The manual
2004.
Scottish Intercollegiate Guidelines Network (SIGN), Control of pain in patients with cancer. 44 1899893 17 2. June
2000.
Valeberg BT, Rustoen T, Bjordal K, Hanestad BR, Paul S, Miaskowski C. Self-reported prevalence, etiology, and
characteristics of pain in oncology outpatients. European Journal of Pain 2008;12(5):582-90.
Wien PJ, McQuay HJ. Oral morphine for cancer pain. Cochrane Database of Systematic Reviews 2007;Issue 3. Art.
No.: CD003868.
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Chapter 2 Pathophysiology of cancer pain and opioid
tolerance
Summary
The neurophysiology of cancer pain is complex: it involves inammatory, neuropathic, ischaemic and
compression mechanisms at multiple sites. A knowledge of these mechanisms and the ability to decide
whether a pain is nociceptive, neuropathic, visceral or a combination of all three will lead to best practice in pain
management. Prolonged opioid use may lead to the development of tolerance, hyperalgesia, dependency or
addiction.
2.1 Introduction
• Cancer pain shares the same neuro-patho-physiological pathways as non-cancer pain.
• It is a mixed mechanism pain, rarely presenting as a pure neuropathic, visceral or somatic
pain syndrome. Rather, it may involve inammatory, neuropathic, ischaemic and compressive
mechanisms at multiple sites.
• Development over time is complex and varied, depending on cancer type, treatment regimes and
underlying concurrent morbidities.
• Opioids are the mainstay of treatment and are associated with tolerance. Tolerance, withdrawal,
dependence and addiction are separate states that are frequently confused and used
interchangeably.
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2.2 Normal Pain Transmission
2.2.1 Peripheral (Figure 1)
Figure 1
• There is a transduction of alterations in the milieu via specialised receptors (i.e. mechano
– pressure, acid sensing ion channels – protons, vallinoid receptors – thermal, tyrosine
kinase A (TrKA), nerve growth factor – inammation, etc.).
• Transmission occurs via primary aerents: Aβ low threshold, myelinated, transmit non-
noxious stimuli; Aδ wide-dynamic range, thin myelinated, transmit noxious stimuli; and C
bres wide-dynamic range, non-myelinated, transmit noxious stimuli.
• Transmission in the primary aerents occurs via depolarisation, with sodium and calcium
channels playing a crucial role to synapse in the dorsal horn.

2.2.2 Spinal cord dorsal horn (Figure 2)
Figure 2
• This is ‘divided’ into laminae: Aβ bres terminate in lamina III; Aδ in lamina I, IV/V; and C
bres in lamina II.
Modulation of the primary aerent inputs occurs. Excitation is via stimulation of post-
synaptic receptors such as: N-methyl D aspartate (NMDA); alpha amino hydroxy methyl
isoxazole propionic acid (AMPA); Substance P; and descending serotonin release.
Inhibition is via stimulation of gamma amino butyric acid (GABA) interneurones,
enkephalin release (opioid receptors) and descending pathways (Noradrenergic or
Serotoninergic).
• Glial cells (microglia and astrocytes) are crucial to the regulation of synaptic glutamate,
and to the initiation and maintenance of neuronal activation.
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2.2.3 Central (ascending) (Figure 3)
Figure 3
• The ascending pathways are the spinothalamic and parabrachial neurones.
• The spinothalamic neurones connect the dorsal horn via the thalamus to the cortex.
These give intensity and the topographic location of stimuli.
• The parabrachial neurones connect lamina I to the hypothalamus and amygdala
structures. These give rise to the aective component of pain.
2.2.4 Central (descending)
• These arise within the periaquaductal grey (PAG) and rostroventromedulla (RVM), and
connect back to the dorsal horn.
• The descending noradrenergic pathways are inhibitory, whilst serotonin can be either
inhibitory or excitatory (via 5HT3 receptors on primary aerents).
2.3 Neuropathic Pain
• This arises from damage to neurones, either peripheral or central (via compression, ischaemia /
haemorrhage, chemical or transection).

• Peripheral damage results in the accumulation of abnormal sodium and calcium channels at the
site of the injury.
• There is a gene expression alteration in the number and character of receptors.
• Damaged neurones discharge spontaneously, and there is cross-talk to normal bres and the
recruitment of silent nociceptors.
• An excessive or absent discharge from primary aerents within the dorsal horn results in an overall
excitation and alteration in the expression of NMDA receptors and a functional loss of opioid and
gabaminergic systems.
• There is resultant hyperexcitation with increased receptive elds, primary and secondary
hyperalgesia and allodynia.
• Higher centres undergo re-mapping and alteration, resulting in an increased excitation of aerent
and cingulate cortices.
2.4 Inammatory Pain
• Peripheral and central mediators of inammation, such as bradykinins, a nerve growth factor,
cytokines, ATP and protons (from dying cells), establish a feed-forward loop that results in the
sensitisation of primary aerents, the recruitment of silent nociceptors and peripheral hyperalgesia.
• The dorsal horn is hyper-excited, which results from an increase in the primary aerent discharge
and the activation of microglia.
• Inhibition is peripheral via the activation of peripheral and central opioid receptors, COX pathways
and descending modulation.
2.5 Visceral Pain
• This is fundamentally dierent from somatic pain. Symptoms include diuse, poorly localised pain
with dierent descriptors (i.e. spasm, heavy feeling).
• Visceral innervation is two-fold: autonomic (i.e. vagal) and spinal.
• Eective stimuli include: chemical, ischaemic, inammatory, compression and distension–
contraction.
• Key transmitters include: peripheral and central serotonin, calcitonin-gene-related peptide,
vasoactive intestinal peptide and kinins.
• Dorsal horn modulation is transmitted centrally via the spino-thalamic cortex to the viscero-sensory
cortex (mid-insular), where viscero-visceral cross-talk occurs.
• Dorsal columns relay predominately to the thalamus, giving rise to strong autonomic responses
and aerent responses.
• There is cross-talk to the somatic sensory cortex and insular cortices.
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2.6 Cancer Induced Pain
• Animal models allow detailed investigation of the neuro-mechanisms of pain, although these can
only give insight into part of the overall complexity. Nevertheless, they do allow the development
and trial of novel therapies. Unfortunately, there are relatively few animal models of cancer induced
pain.
2.6.1 Cancer-Induced Bone Pain (CIBP) (Figure 4)
Figure 4
• Over the past decade, several murine models of contained bone tumour growth (cancer,
sarcoma and myeloma cells) have been developed, and pain development parallels the
clinical picture.
• Bone is highly innervated with C bres, which are triggered by an inammatory initrate
(secondary to cancer cells) and others (including acid, cytokine, growth factors, etc.),
along with primary aerent destruction (following osteoclast activation).
• The dorsal horn shows a unique pattern of excitation (neither pure neuropathic nor
inammatory), increased wide-dynamic range neurones in lamina I cells (50% compared
with 25% in normals), hyper-excitation lamina I and V, increased glia activation and
dynorphin expression.
• There is attenuation of CIBP via opioids (although this is less ecacious than for
inammation), gabapentin and peripheral inhibitors such as osteoprogeterin (inhibits
osteoblast-osteoclast) TrKA receptor antagonist and endothelial receptor antagonists.

2.6.2 Cancer Therapy Induced Pain
• Murine models of chemotherapy induced pain allow the investigation of cancer
neuropathies with particular interest in taxols, platins, thalidomide, bortezomib, etc., or
direct inoculation of the tumour cells around nerves.
• Cancer neuropathies have disadvantages in transient aerent alterations and a decline
in motor function. Local inammatory inltrates and neuropathic damage illustrate the
unique syndrome.
• Chemotherapy induced neuropathies have illustrated the diverse and unique nature
of damage, including taxol interruption of microtubular aggregation, accumulation in
dorsal root ganglia and the activation of a neuro-immune reaction, which may account
for the side-eects of taxols.
2.7 Opioid Therapy (Figure 5)
Figure 5
• This remains the mainstay analgesia for all cancer pain.
• The practice of opioid switching in order to improve analgesia while minimising side-eects is
recommended after careful consideration and titration. While this is poorly explained at a receptor
level (theories include genomic variations, altered internalisation or the activation of receptors to
dierent opioids), clinical evidence in its favour is building.
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2.7.1 Opioid hyperalgesia
• Increasing doses of opioids can be associated with hypersensitivity of the skin to touch
and a lack of analgesic response. It is necessary to taper the dose in order to restore
ecacy. This state is known as hyperalgesia (Compton, 2001; Doverty, 2001).
• The cellular mechanisms of opioid induced hyperalgesia have much in common with
those of neuropathic pain and opioid tolerance (IASP, 2008).
2.7.2 Opioid tolerance
• Clinical tolerance to opioids is complex. It is dened as a reduced eect for an equivalent
dose or the requirement of increased doses to attain the same eect.
• Physiological receptor internalisation, uncoupling, decreased or increased activation and
altered expression occur over varying periods from minutes to days, and are not followed
by clinical scenarios.
• Tolerance may occur to nausea, vomiting, respiratory depression and sedation.
• No tolerance is demonstrated to constipation or pupil constriction.
• Analgesic tolerance is easily demonstrated in rat or mouse models.
• Analgesic tolerance in humans is complex and the subject of heated debate. Many
papers suggest that no signicant analgesic tolerance occurs (patients continue on the
same dose for months and years), while others suggest that incomplete cross-tolerance
allows increased ecacy from dierent opioids.
Adjuvants are increasingly important for attaining good analgesic control.
2.7.3 Dependence
• Dependence (physical or psychological) can occur in many patients.
• Dependence is dierent from addiction, since patients remain compliant through opioid
alterations, if the side-eects are controlled.
• Physical dependence results in withdrawal syndromes (upon dose reduction).
• Psychological dependence arises when a behavioural connection between analgesia
and opioids is established.
• Fear of pain or incomplete analgesia can induce requests for increased opioids, which
can be mistaken for addiction. This subsides with good analgesia, even if this is achieved
via non-opioids. This is sometimes called pseudo-addiction.
2.7.4 Addiction
• Addiction is characterised by drug seeking behaviour (multiple sources, legal and illegal),
compulsive use, abrupt withdrawal reactions, non-compliance with suggested opioid
changes and craving.

• Addiction is a genetic, behavioural, physiological and environmental state that occurs
in a minority of people exposed to opioids. It is more common when opioids are used
outside the context of pain /analgesia.
• Analgesia in opioid addicted people is highly specialised and specialist referral (pain or
palliative medicine teams) is recommended in any case of concern for a patient..
2.7.5 Withdrawal
• Physical withdrawal, including abdominal cramps, diarrhoea and sweating, occurs in
almost all patients to some extent upon reduction of opioid dose.
• Psychological withdrawal occurs in many patients who fear a resurgence of previous
pain. This settles rapidly when pain does not reoccur.
• Withdrawal is not a sign of addiction or dependence.
2.8 Cannabinoids (Figure 6)
Figure 6
• Endocannabinoids are important in central inhibition.
• They act primarily on CB1 neuronal receptors.
• CB2 receptors are primarily immune cells, including glia.
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• There is some evidence for other cannabinoid receptors.
• Cannabinoids are potentially an important clinical alternative to opioids for analgesia.
• There are problems with a lack of specicity and they are highly lipophilic, thus having non-receptor
bound eects (via plasma membrane diusion).
References
Compton P, Chanuvastra VC, Ling W. Pain intolerance in opioid-maintained former opiate addicts. Eect of long-
acting maintenance agent. Drug and Alcohol Dependence 2001;63:139-146
Doverty M, White JM, Somogyi AA, Bochner F, Ali R, Ling W. Hyperalgesic responses in methadone maintenance
patients. Pain 2001;90:91-96.
Hunt SP, Mantyh PW. The molecular dynamics of pain control. Nature Neuroscience 2001;2:83-91.
International Association for the Study of Pain (IASP). Opioid-induced hyperalgesia. Pain Clinical Updates
2008;XVI(2):1-4.
Further reading
Carpenter KJ, Dickenson AH. Molecular aspects of pain research. The Pharmacogenomics Journal 2002;2(2):87-95.
Cervero F, Laird JM. Understanding the signalling and transmission of visceral nociceptive events. Journal of
Neurobiology 2004;61(1):45-54.
Suzuki R, Dickenson AH. Neuropathic pain: nerves bursting with excitement. Full journal 2001;11(12):17-21.
Suzuki R, Rygh LJ, Dickenson AH. Bad news from the brain: descending 5-HT3 pathways can control spinal pain
processing. Trends in Pharmacological Sciences 2004;25(12):613-7.
Tracey I. Functional connectivity and pain: how eectively connected is your brain? Pain 2005;116(3):173-4.
Tsuda M, Inoue K, Salter MW. Neuropathic pain and spinal microglia: big problem from molecules in small glia.
Trends in Neuroscience 2005;28:101-7.
Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet
1999;353:1959-64.

Chapter 3 Cancer pain assessment
Summary
Accurate and meaningful assessment and reassessment of pain is essential and optimises pain relief. History,
examination, psychosocial assessment and accurate record keeping should be routine, with pain and quality of
life measurement tools used where appropriate.
3.1 Introduction
• People with cancer can report the presence of several dierent anatomical sites of pain which
may be caused by the cancer, by cancer treatment, by general debility or by concurrent disorders
(Twycross, 1996).
• Inadequate assessment of pain and a lack of documentation are thought to be the greatest barriers
to eective pain relief (Herr, 2004); therefore, enquiries into the presence of pain should be included
in the assessment of all patients who are diagnosed with cancer.
3.2 Assessment
• All patients diagnosed with cancer who report pain should undergo a comprehensive assessment
and reassessment of pain. Wherever possible, the patient should be involved in the assessment and
reassessment of their pain (Cleeland, 1994).
• In an acute care setting, the initial pain assessment should be undertaken on admission. There
should at least be a daily reassessment of pain; however, this may be more frequent depending on
the severity of pain, the level of distress or any new reports of pain (de Rond, 1999).
• In the primary care setting, pain should be assessed on each visit to the patient. Timing of this
assessment will depend on patient’s individual circumstances (de Rond, 1999).
• In primary care, patients and their carers should be given and taught to use a pain diary in order to
monitor pain levels, medication requirements, the eectiveness of analgesia and any side-eects of
medication (Allard, 2001).
• Any evidence of the initial pain assessment, the reassessment and the eectiveness of analgesia
must be documented within the patient’s record (NMC, 2004).
3.2.1 Core Elements of Initial Assessment
These will include:
• a detailed history to determine the presence of persistent pain, breakthrough pain and
their eect on function.
• a psychosocial assessment.
• a physical examination.
25

26
• a diagnostic evaluation for signs and symptoms associated with common cancer pain
syndromes (Miaskowski, 2005).
3.2.2 Breakthrough pain
Breakthrough pain is dened as a transitory are up of moderate to severe pain in patients with
otherwise stable persistent pain (Bennett, 2005; Portenoy, 1990).
Factors to consider when assessing for breakthrough pain include:
• the presence of breakthrough pain.
• the frequency and number of episodes per day.
• the duration, with the time in minutes.
• the intensity and the time to peak in severity.
• the description of breakthrough pain.
• any precipitating factors.
• a current and previous analgesic history (Hwang, 2003).
3.2.3 Ongoing Assessment and Reassessment of Pain
People with cancer who report pain should be assessed using a formalised pain assessment tool which
reects the multidimensional nature of pain, an example being the Brief Pain Inventory (Cleeland,
2004b). This will provide the opportunity to identify and record each individual site of pain experienced
by the patient and its impact. The reassessment should include the eectiveness of any pain
management strategies employed (SIGN, 2000).
This should include:
• the location of pain.
• the characteristics/a description of the pain.
• the severity/intensity of the pain.
• the duration of the pain.
• any aggravating factors.
• any relieving factors.
• the eect of pain on function and activities of daily living.
• the impact on quality of life.
• the impact on psychological well-being.
• any social impact.

• any spiritual impact.
• pain expectations.
• medication – current and previous analgesics.
• opioid toxicity.
• complementary interventions.
• the outcome.
A comprehensive assessment of pain must be carried out following any new reports of pain. This
should include a diagnostic evaluation and may result in a review of the pain management plan. Any
new complaint of pain could indicate a change in the underlying pathological process and may require
urgent medical attention.
3.3 Psychosocial factors
Fear, anxiety, depression and a lack of sleep have been reported as increasing pain and suering in people with
cancer (Anderson, 2003; Portenoy, 1994). A comprehensive pain assessment should include the personal and
social inuences that determine how pain is experienced and perceived (Miaskowski, 2005).
Patients displaying signs of distress should undergo a more detailed assessment of their emotional distress and/
or depression. Patients should have the opportunity to express their emotions, thoughts, fears and expectations
regarding their pain. Factors associated with the patient’s treatment which may contribute to their emotional
distress and/or depression must be included in the assessment.
An assessment of the psychosocial factors inuencing the experience of pain will include:
• the patient’s understanding of their condition.
• what the pain means to the individual and their family.
• how the pain may impact upon relationships within the patient’s family.
• whether the pain inuences the patient’s mood.
• changes in mood.
• coping strategies adopted by the patient.
• the patient’s sleep pattern.
• any economic impact.
3.4 Spiritual factors
Patients’ spiritual beliefs can inuence their health beliefs and sense of well-being.
27

28
The concept of spiritual pain requires practitioners to go beyond the bounds of clinical treatments and be
prepared to devote time to provide supportive and understanding care (Mako, 2006). Spiritual care is not
necessarily religious. However, religious care, at its best, should always be spiritual (NHS HDL, 2002). Spiritual care
is given in a one-to-one relationship, is completely person-centred and makes no assumptions about personal
conviction or life orientation (NHS HDL:76:2002).
3.5 Special Groups
Certain groups of individuals may be at a higher risk of under treatment for cancer pain. These groups include:
• older people.
• the cognitively impaired.
• people whose rst language is not English.
• known or suspected substance abusers.
• patients at the end of their lives..
(NHS QIS, 2006; Miaskowski, 2005).
People who are being treated for cancer may also be at risk of developing pain syndromes as a direct result of
cancer treatment strategies (Portenoy, 1999). Practitioners should use appropriate strategies to identify people at
risk of under-treatment for cancer pain.
Pain assessment tools to assess cancer pain in special groups should be made available.
3.6 Barriers to Accurate Assessment
• The main barrier to optimal eective pain relief is the inadequate assessment of pain (Herr, 2004).
Healthcare professionals working with cancer patients should be trained in pain assessment
methods. Pain assessment should take place at regular intervals following the start of any new
treatments and at each new report of pain.
• Patients with cancer may have a number of fears about their pain and might be reluctant to report
pain. Pain control can be enhanced if management strategies include interventions on relieving
anxiety and depression (Loftus, 2007). Therefore, pain and its management should be discussed
with the patient and their families. Patients with cancer pain should be encouraged to be active
participants in the management of their own pain.
References
Allard P, Maunsell E, Labbe J, Dorval M. Educational interventions to improve cancer pain control: a systematic
review. Journal of Palliative Medicine 2001;4(2):191-203.
Anderson KO, Getto CJ, Mendoza TR, Palmer SN, Wang XS, Reyes-Gibby CC, Cleeland CS. Fatigue and sleep
disturbance in patients with cancer patients with clinical depression, and community-dwelling adults. Journal of
Pain and Symptom Management 2003;25(4):307-318.

Bennett DS, Burton AW, Fishman S, Fortner B, McCarberg W, Miasskkowski C, Nash DB, Pappagallo M, Payne R, Ray
J, Viscusi ER, Wong W. Consensus panel recommendations for the assessment and management of breakthrough
pain. Pharmacy and Therapeutics 2005;30(5):296-301.
Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Annals of the Academy of Medicine
Singapore 1994;23(2):129-138.
Cleeland C, Gonin R, Hateld A, Edmonson J, Blum R, Stewart J, Pandya KJ. Pain and its treatment in outpatients
with metastatic cancer. New England Journal of Medicine1994b;330(9):592-596.
de Rond M, de Wit R, van Dam F, van Campen B, den Hartog Y, Klievink R, Nieweg R, Noort J, Wagenaar M, van
Campen B. Daily pain assessment: Value for nurses and patients. Journal of Advanced Nursing 1999;29:436-444.
Herr K, Titler MG, Schilling ML, Marsh JL, Xie X, Ardrey G, Clarke MS, Everett LQ. Evidence based assessment of acute
pain in older adults: current nursing practices and perceived barriers. Clinical Journal of Pain 2004;20(5):331-340.
Hwang SS, Chang VT, Kasimis B. Cancer breakthrough pain characteristics and responses to treatment at a VA
medical centre. Pain 2003;101:14(1-2):55-64.
Loftus LA, McIntosh J, Peace E, Tolsen D. Implementation of SIGN 44 guidelines for managing cancer pain in a
community setting. International Journal of Palliative Nursing 2007;13(7):315-324.
Mako C, Glaek K, Poppito SR. Spiritual pain among patients with advanced cancer in palliative care. Journal of
Palliative Medicine 2006;9(5):1106-1113.
NHS Quality Improvement Scotland, Management of Chronic Pain in Adults, Best Practice Statement, Edinburgh
2006.
Miaskowski C, Cleary J, Burney R, Coyne P, Finley R, Foster R, Grossman S, Janjan N, Ray J, Syrjala K, Weisman S,
Zahrbrock C. Guideline for the management of cancer pain in adults and children. American Pain Society Clinical
Practice Guidelines Series, No 3; American Pain Society 2005, Glenview, Illinois.
NHS HDL.76, Spiritual Care in Scotland, Guidelines on Chaplaincy and Spiritual Care in the NHS in Scotland,
Scottish Executive Health Department 2002, Edinburgh.
Portenoy RK, Hagen NA. Breakthrough pain: denition, prevalence and characteristics. Pain1990;41(3):273-281.
Portenoy RK, Thaler HT, Kornblith AB, Lepore JM, Friedlander-Klar H, Coyle N, Smart-Curley T, Kemeny N, Norton
L, Hoskins W. Symptom prevalence, characteristics and distress in a cancer population. Quality of Life Research
1994;3(3):183-189.
Portenoy RK, Lesage P. Management of Cancer Pain. Lancet 1999;353(9165):1695-1700.
Scottish Intercollegiate Guidelines Network (SIGN 44). Control of pain in patients with cancer. NHS Quality
Improvement Scotland 2000, Edinburgh.
The NMC Code of Professional Conduct: Standards for Conduct, Performance and Ethics. Nursing and Midwifery
Council 2004, London.
Twycross R, Harcourt J, Bergl S. A survey of pain in patients with advanced cancer. Journal of Pain and Symptom
Management 1996;12(5):273-282.
29

30

Chapter 4 Oncological management of cancer pain
Summary
Radiotherapy, chemotherapy, hormones, bisphosphonates and surgery are all used to treat and palliate cancers.
Combining these treatments with pharmacological and non-pharmacological methods of pain control can
optimise pain relief, but the limitations of these treatments must also be acknowledged. Specically, skeletal pain,
abdomino-pelvic pain and headache are discussed.
4.1 Overview of Cancer Treatments for Pain
• Successful oncological management of any tumour, if it is only palliative, can result in a signicant
improvement in pain relief.
• Combining cancer treatments with pharmacological and non-pharmacological methods of pain
control can result in optimum pain management.
• However, it should be acknowledged that oncological treatments themselves may induce
persistent pain in some patients (see chapter 11).
• Cancer treatment includes loco-regional treatments, either surgery or radiotherapy, and systemic
therapy with chemotherapy, hormone therapy and biological modiers.
4.1.1 Surgery
Major surgery is rarely appropriate for a patient with advanced cancer and metastatic pain, and specic
indications exist for surgical intervention (Table 1).
• A pathological fracture of a long bone is a clear indication for internal surgical xation,
following which rapid pain relief and the restoration of function can be achieved.
• A vertebral fracture may require stabilisation to avoid spinal cord compression, for
example by open surgery or by vertebroplasty.
• Progressive ascites can cause persistent abdominal pain and discomfort. Repeated
paracenteses may not be possible or appropriate, and a Le Veen shunt draining the
ascitic uid into the superior vena cava can be a valuable means of resolving this
situation.
4.1.2 Radiotherapy
Radiotherapy is usually delivered as external beam treatment; common indications are shown in Table
2.
• Radiation may also be delivered by systemic radioisotopes, and this is particularly
recommended in the management of scattered metastatic bone pain, for example
by using bone-seeking isotopes. Such treatments are predominantly used for primary
tumours associated with osteoblastic metastases, for example prostate and breast
cancers.
31

32
4.1.3 Chemotherapy
• Chemotherapy may also provide valuable pain relief for a patient with widespread
metastatic disease; common indications of this are shown in Table 3.
• The principal limitation of chemotherapy is related to the limited tumour
chemosensitivity encountered in advanced and recurrent cancer, e.g. breast, non-small
cell lung cancer and colorectal cancer. However, some tumours that are associated with
widespread severe metastatic bone pain (e.g. multiple myeloma and small cell lung
cancer) remain more sensitive and chemotherapy can have a major palliative role.
4.1.4 Hormone therapy
Breast and prostrate cancer account for a large number of patients who present with metastatic
disease and cancer pain and who are hormone sensitive.
• Anti-androgen therapy for prostate cancer results in dramatic pain relief for many
patients, with response rates of over 90% on initial exposure but the median duration of
response is between 18 months and two years.
• Breast cancer may respond to second and third line hormone treatment using anti-
oestrogen drugs like tamoxifen or toremifene, aromatase inhibitors such as anastrozole
and letrozole, progestogens such as megestrol or medroxyprogesterone acetate and,
occasionally, androgens. These hormone manoeuvres may be used sequentially, with
useful responses for the patient with widespread disease and metastatic pain.
4.1.5 Bisphosphonates
• Bisphosphonates are used increasingly in the management of cancer-induced bone pain
(CIBP). They are drugs with poor oral bio-availability and are usually given as intravenous
infusions, with pamidronate and clodronate being the most commonly used, although
these may in due course be replaced by newer, more potent, drugs such as zolendronate
and ibandronate.
• There is good evidence that in the adjuvant setting bisphosphonates reduce morbidity
from bone metastasis, for example by reducing skeletal events and preventing the need
for radiotherapy. A recent review indicated that regular use of bisphosphonates reduced
the number of skeletal-related events in numerous cancers (Ross, 2003).
• A Cochrane review in 2000 concluded that, despite methodological limitations, the
evidence suggested that bisphosphonates provide modest pain relief for patients with
bony metastases where analgesics and/or radiotherapy are inadequate (Wong, 2002).
4.2 Specic pain problems in cancer patients
4.2.1 Skeletal pain
Skeletal pain in cancer patients is most commonly associated with bone metastese; however, patients
may have comorbidities (Table 4).

• In some patients there will be a single, solitary site of severe pain (while other
documented bone metastases are asymptomatic), whereas others may have scattered
multi-focal pain often itting from one area to another, which is the clinical scenario.
Combining radiotherapy with pharmacological and non-pharmacological management
is generally recognised as the most eective treatment in this setting.
• First line pharmacological approaches include paracetamol and non-steroidal anti-
inammatory drugs (NSAIDs). Adjuvant analgesics include skeletal muscle relaxants
(diazepam, baclofen), bisphosphonates and, occasionally, corticosteroids for intractable
scattered pain.
• Neuropathic pain may be a feature that is particularly related to vertebral metastasis
requiring other specic treatment.
• Where a pathological fracture of a long bone is encountered, internal surgical xation
remains the optimal management. Intraspinal analgesia or a nerve block is usually
indicated if surgery is not possible for a pathological fracture of a long bone, since
analgesia and radiotherapy alone are not sucient to control the movement-related pain
associated with this situation. One alternative may be percutaneous cervical cordotomy
to treat unilateral incident pain resulting from a solitary long bone pathological fracture.
4.2.1.1 Localised external beam radiotherapy
• Localised external beam radiotherapy for metastatic bone pain is the usual
modality for localised bone pain, and this has been the subject of a large
number of randomised controlled trials and two Cochrane reviews (McQuay,
1997; Sze, 2003). These have conrmed its ecacy, with a complete response
rate of 32 - 34% and NNT for complete response of 3.9 (95% CI 3.5-4.4). Relief
was achieved by 60% of patients, with an NNT of 3.6 (95% CI 3.2-3.9). Single
doses of 8 to 10Gy appear to be as eective as more prolonged, high dose
schedules and response rates are generally not predicted by tumour histology.
• Toxicity is mild and is related to the site of treatment; treatment of areas
which include signicant amounts of bowel, such as the lumbosacral spine
and pelvis for example, will result in nausea and increased bowel frequency
in 20 to 30% of patients (Yarnold, 1999). These symptoms will respond to
medication and are self-limiting over a period of 10 to 14 days. Peripheral sites
in the upper and lower limbs are, in general, associated with no signicant
side-eects.
• The pattern of pain relief after external beam radiotherapy for localised bone
pain has been shown to evolve consistently over four to six weeks from
treatment, with 50% of patients responding within two weeks of treatment
and reaching a plateau two to four weeks later when, on actuarial analysis,
around 80% of patients will have recorded a response.
• A pathological fracture may be treated with external beam radiotherapy
where it is not surgically operable, for example with the ribs, vertebral bodies
and pelvic bones. After receiving doses similar to those given for local bone
pain, healing is seen over a period of six to 12 weeks after treatment, preceded
by the early relief of bone pain.
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34
4.2.1.2 Wide eld external beam radiotherapy
• Wide eld external beam radiotherapy is used to treat multiple sites of
bone pain. This form of radiotherapy is typically dened as upper hemibody
radiotherapy, covering the ribs and cervico-dorsal spine, or lower hemibody
radiotherapy, covering the lumbo-sacral spine, pelvis and lower limbs. This
technique can be used sequentially to cover the entire skeleton, but there
needs to be a four to six week recovery period in the treated area for the
remainder of the bone marrow is exposed to radiation.
• A simple two-fraction schedule delivering 8Gy over two days is used. Similar
response rates to external beam radiotherapy have been reported, with a
much more rapid pattern of response: 25% of patients responded within
the rst 24 hours in some studies (McQuay, 1997; Salazar, 2001). Inevitably,
treating larger volumes results in greater toxicity when this technique is used,
and around two-thirds of patients will report nausea and increased bowel
frequency.
4.2.1.3 Radioisotope treatment
• Radioisotope treatment involves the intravenous administration of a bone
seeking radio-isotope that delivers localised radiotherapy to multiple sites
of bone metastasis. This is achieved using isotopes which are attracted
physiologically to sites of bone mineralisation. Strontium (89Sr) is currently the
most commonly-used isotope.
• Radioisotope treatment for metastatic bone pain has a similar ecacy to wide
eld external beam irradiation, but is associated with less toxicity and lower
transfusion requirements (Bauman, 2005). Meta-analysis has not dened an
individual NNT for radio-isotope therapy (McQuay, 1997; Sze, 2003).
• Although of similar ecacy to external wide eld radiotherapy, this treatment
has a better toxicity prole and the relative ease of delivery has meant that, in
a wealthy healthcare system, radio-isotope therapy has become the treatment
of choice in this setting. However, where this is not available, wide eld
external radiotherapy can achieve equivalent pain relief.
• A further specic role of radio-isotope therapy relates to bone metastases
from thyroid carcinoma. Around 80% of dierentiated thyroid cancers will
concentrate radio-iodine, and this therefore provides a potential therapeutic
isotope for these metastases at any site in the body. Radioiodine is given
orally in this setting in doses of 3,000 to 5,000 MegaBequerels (MBq) following
ablation of the thyroid gland.
4.2.1.4 Chemotherapy and hormone therapy
Sections 4.1.3 and 4.1.4 describe the palliative role of chemotherapy and hormone therapy.
This section draws attention to their role in the management of bone metastases.
• Quite dramatic responses can be achieved within a few days of starting anti-
androgen therapy in prostate cancer. The response in metastatic breast cancer
is generally slower and additional measures for pain relief are usually required
in the rst few weeks after starting hormone therapy.

• Hormone therapy, as with any other treatment which may induce acute new
activity in bones, may be associated with a transient are-up of pain that
needs to be managed with the appropriate manipulation of analgesia.
4.2.2 Thoracic pain
• The common causes of intra-thoracic pain in malignancy are non-small cell lung cancer
and mesothelioma. The pain is often poorly localised in respect to the primary tumour
site and, in mesothelioma, neuropathic pain resulting from local inltration of the
intercostal nerves may become a prominent feature.
• The general approach that was outlined above, therefore, using dose-escalating
analgesics through the WHO analgesic ladder, will be required for most patients, and this
can be supplemented by other, more specic, therapies. Where chest wall inltration has
occurred, NSAIDs may be of value; and where there is neuropathic pain, anti-convulsants
and anti-depressants will have an important role. Intercostal nerve blocks are also
very eective in certain patients. More aggressive anaesthetic interventions, such as
intraspinal analgesia or cordotomy, may be required, especially in mesothelioma.
4.2.3 Abdomino-pelvic pain
• Abdominal pain in malignancy is typically visceral due to hepatic metastasis or bowel
obstruction. Pelvic pain may have a visceral component, but is also likely to have a
neuropathic element with pain resulting from lumbo-sacral plexus inltration.
• Hepatic metastases typically cause pain as an enlargement of the liver results in the
capsule being stretched at the point of the sensory innervation.. In general, unless there
is gross hepatic dysfunction, the metabolism of the common drugs in the WHO ladder
are not aected by the presence of liver metastasis. Steroids may be of value in reducing
hepatic oedema and liver pain. Where a chemo-sensitive tumour is present, then
reduction of the liver size using chemotherapy should be considered. However, whilst
hormone therapy may reduce hepatomegaly from liver metastasis, the response is often
slow, taking several months. Two randomised, controlled trials have addressed the role
of hepatic irradiation in advanced malignancy and concluded that eective palliation
of pain is achieved in 80% of cases and systemic symptoms can be achieved in 45% of
selected cases (Borgelt, 1981).
• Splenomegaly may also be a cause of abdominal pain. Typically, this will be due to a
haematological malignancy, such as chronic granulocytic leukaemia or lymphoma. These
are chemosensitive tumours and chemotherapy will therefore be the main line of attack.
High dose steroids will also be of value and, on occasions in chemo-resistant disease,
either surgical splenectomy or splenic irradiation will have a role in pain relief.
• Pancreatic pain is a characteristic severe visceral pain radiating into the back and is often
poorly controlled with analgesics, even with the titration of strong opioids. Randomised
controlled trial evidence has conrmed the positive role of a neurolytic coeliac plexus
block in this setting, with superior results in terms of pain relief over analgesics alone
(Eisenberg, 1995).
• Pelvic pain, if not due to bone metastases, will most commonly result from a presacral
recurrence of rectal carcinoma or a pelvic recurrence of cervical cancer. Lumbo-sacral
plexus inltration is common, resulting in severe pain with a major neuropathic
component.
35

36
4.2.4 Headache
• A headache resulting from malignant disease may arise from raised intracranial pressure
due to brain metastasis or progressive incurable primary brain tumours. It may also be a
result of hydrocephalus, typically from a tumour in the mid brain or posterior fossa that
is obstructing the aquaduct. Diuse meningeal disease may cause a communicating
hydrocephalus, which is less commonly associated with a headache. It is important to
remember that a headache may also be due to anxiety and depression and that other
common, non-malignant causes of headache may be found in patients with advanced
cancer, such as tension headache and migraine.
• Where there is raised intracranial pressure, then steroids are of value. A randomised
controlled trial suggested that relatively low doses of dexamethasone are as eective as
higher doses, with 4mg being equivalent to 8mg or 16mg and such doses are associated
with fewer steroid induced side-eects (Vecht, 1994). The length of treatment should be
as short as possible and any maintenance treatment should be at the lowest possible
dose to minimise steroid-induced side-eects.
• Brain metastasis can be palliated successfully with brain irradiation (Hoskin, 2000). A
solitary metastasis may be best treated with surgical decompression and post-operative
radiotherapy; multiple metastases should be treated with whole brain radiotherapy.
Chemotherapy is also of value in brain metastasis where there is a chemosensitive
tumour and should always be considered for haematological malignancies, including
non-Hodgkin’s lymphoma, germ cell tumours, small cell lung cancer and breast cancer.
• Primary brain tumours are best managed by surgical debulking followed by post-
operative radiotherapy. Dexamethasone and, in acute situations, mannitol may be
required to control intracranial pressure, which is the usual cause of headache. High dose
(60Gy) chemoradiation for primary gliomas is now the standard treatment for patients
with good performance status.
• Obstructive hydrocephalus is best treated by surgical decompression followed by
appropriate local treatment to the tumour, which will often include radiotherapy. An
internal shunt may be eective when decompression is not possible.
• Other associated causes of headaches should also be considered, including cervical
spine metastasis, for which local radiotherapy will have an important role, and tumours
of the head and neck region, particularly those involving the sinuses or orbit. Appropriate
surgical resection or radiotherapy will be considered for these tumours along with
pharmacological management of pain.
Table 1 Indications for surgery in management of cancer pain
Pain Cause Surgery
Bone pain Pathological fracture Internal xation
Headache Obstructive hydrocephalus
Tumour bulk
Shunt
Debulk
Dysphagia Oesophageal tumour Stent
Abdominal distension Ascites Drain and shunt
Soft tissue pain Necrotic tumour Toilet resection

Table 2 Indications for radiotherapy in management of cancer pain
Pain Cause
Bone pain Metastases
Pathological fracture (non-surgical e.g. rib / pelvis)
Headache Primary cerebral tumour
Brain metastases
Abdominal pain Hepatomegaly
Pelvic pain Local tumour inltration
Chest pain Primary lung cancer
Mesothelioma
Soft tissue pain Local tumour inltration
Table 3 Indications for chemotherapy in the management of cancer pain
Pain Cause Primary tumour types
Bone pain Bone metastases Myeloma
Breast cancer
Lung cancer
(small and non-small cell)
Headache Brain metastases Germ cell tumours
Lymphoma and Leukaemias
[Breast cancer]
[Small cell lung cancer]
Abdominal pain Ascites
Subacute obstruction
Ovary
Colorectal
Stomach
Pancreatic pain Pancreas
Pelvic pain Local tumour inltration Colorectal
Ovary
Cervix
Chest pain Local tumour inltration Lung cancer
(small and non-small cell)
Metastases from chemosensitive sites e.g. breast,
colorectal [Mesothelioma]
Note: [ ] indicates tumours with only modest (<50%) response rates when other modalities e.g. radiotherapy may be preferred.
Table 4 Causes of bone pain in cancer patients
Metastases
Fracture
Degenerative bone disease
e.g. osteoarthritis
Bone marrow pain
Non-metastatic hypertrophic osteoarthropathy
e.g. HPOA (hypertrophic pulmonary osteoarthropathy)
Other bone disease e.g. Paget’s
37

38
Table 5 Chemosensitivity of primary tumours commonly metastasising to bone
Primary site Sensitivity *
Myeloma High
Bronchus High
Breast High
Rectum Mid
Oesophagus Mid/low
Prostate Low
Thyroid Low
Kidney Low
* High = >50% response rate
Mid = 25-50% response rate
Low = <25% response rate
Figure 1 Overview of the management of metastatic bone pain
For continuing pain, despite of all above, consider anaesthetic intervention.
*** systematic review of meta-analysis
** one or more well-designed randomized controlled trials
* non-randomized controlled trials, cohort study, etc.

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on skeletal morbidity in metastatic cancer. British Medical Journal 2003;327: 469-472.
Salazar OM, Sandhu T, DaMotta NW, Lanzos-Gonzales E, Mouelle-Sone A, Moscol A, Zaharia M, Zaman S, Perez
Escutia MA. Fractionated half3 body irradiation (HBI) for the rapid palliation of widespread, symptomatic
metastatic bone disease: a randomised phase III trial of the International Atomic Energy Agency (IAEA).
International Journal of Radiation Oncology Biology Physics 2001;50:765-775.
Sze WM, Shelley MD, Held I, Wilt TJ, Mason MD. Palliation of metastatic bone pain: single fraction versus
multifraction radiotherapy a systematic review of randomised trials. Clinical Oncology 2003;15;6:345-352.
Vecht CJ, Hovestadt A, Verbiest HBC, van Vliet TJ, van Putten WLJ. Dose-eect relationship of dexamethasone on
Karnofsky performance in metastatic brain tumours: a randomised study of 4.8 and 16 mg per day. Neurology
1994;44:675-680.
Wong R, Wien PJ. Bisphosphonates for the relief of pain secondary to bone metastases. Cochrane Database
Systematic Review 2002: CD002068.
Yarnold JR. For the Bone Pain Trial Working Party. 8 Gy single fraction radiotherapy for the treatment of metastatic
skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up.
Radiotherapy Oncology 1999;52:111-121.
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40

Chapter 5 Modern pharmacological management of cancer
pain
Summary
Opioids remain the mainstay of cancer pain management, but the long-term potential complications of tolerance,
dependency, hyperalgesia and the suppression of the hypothalamic/pituitary axis should be acknowledged
and managed in both non-cancer and cancer pain, as well as the well-known side-eects such as constipation.
NSAIDs, antiepileptic drugs, tricyclic antidepressants, NMDA antagonists, sodium channel blockers, topical agents
and the neuraxial route of drug administration each have their place in the management of complex cancer pain.
5.1 WHO analgesic ladder
• The prevailing model since 1986 for the management of cancer pain, and latterly some forms of
chronic non-malignant pain, has been the WHO 3-step analgesic ladder (WHO, 1990).
• This guideline was born from a need for a simple, public health tool, especially for developing
countries with little access to opioids. It was not, in the modern sense, evidence-based in its
construction (Meldrum, 2005).
• According to the WHO ladder, if pain occurs, there should be prompt administration of analgesic
drugs via the oral route until the patient is free of pain. It also advises that drugs should be given “by
the clock”, that is every 3-6 hours, rather than “on demand” in order to continue to provide “freedom
from pain”.
• The WHO ladder states that non-opioids (Paracetamol & NSAIDs) should be administered rst,
followed by weak opioids (Codeine) and then, if required, strong opioids (Morphine).
• It also recommends the use of adjuvant drugs to calm fears and anxieties (WHO, 1990).
• This three-step approach of administering the right drug in the right dose at the right time is
inexpensive and has shown to be eective in 45% to 100% of cases worldwide (Ferreira, 2006).
• The WHO approach relies heavily on the use of opioids, in particular morphine, and the role of
“adjuvants” is not clearly dened, although this is usually interpreted as the addition of paracetamol
and NSAIDs.
5.2 Opioids
• Opioids remain the mainstay of cancer pain management. When used as the sole analgesic, high
doses are often required, which may be associated with troublesome side-eects, particularly
sedation, constipation and even respiratory depression.
• Side-eects can be managed with the appropriate use of anti-emetics and laxatives in the majority
of cases.
41

42
• Cognitive disturbances, tolerance and opioid-induced hyperalgesia may occur when high doses of
opioids are used for a prolonged period (Ballantyne, 2007).
• The eectiveness of long-term use of opioids for persistent non-cancer pain has been
disappointing. Studies show limited ecacy, and addication had developed in approximately
18% of cases (Ballantyne, 2007), with increasing evidence of the suppression of the hypothalamic/
pituitary axis and immune suppression.
• It is well established that patients are going through long-term opioid therapy develop
hypogonadotrophic hypogonadism and also opioid-induced androgen deciency - OPIAD (Daniell,
2006).
• Long-term opioid therapy contributes towards bone demineralisation, thus predisposing the
patient to osteoporosis (Vestergaard, 2006), and also signicantly reduces serum HDL levels (Abs R,
2000).
• The analgesic eects of opioids are primarily achieved through the activation of G-protein coupled
receptors on neurons, which open potassium channels to hyperpolarise their membranes. Opioids
dier in terms of their anity to bind to the receptor sites, their pharmocokinetics and their
physicochemical properties. This means that certain opioids will have advantages over others due
to diering side-eect proles, routes of administration, development of tolerance and propensity
for immunomodulation (Meert, 2005). Indeed, the current trend of ‘opioid switching’ may be partly
driven by the need to move between incompletely cross-tolerant opioids in order to minimise their
inherent toxicities (Holdcroft, 2003).
5.2.1 Routes of administration
• Modern technologies for administration, including transdermal, oral transmucosal and
spinal delivery, bring advantages in terms of increased bio-availability, reduced side-
eects and/or convenience for many patients (Clark, 2004).
• Buccal, sublingual and intra-nasal routes can be used to deliver rapid-acting opioids on
demand in addition to the “around the clock”, long-term opioids providing background
analgesia.
• Epidural and intrathecal routes for the administration of opioids (morphine, diamorphine
and hydromorphone) with or without local anaesthetics increases eectiveness,
while reducing side-eects, particularly drowsiness and constipation, and should be
considered when pain cannot be controlled by simpler means (see section 8.8).
5.3 “Adjuvant “ analgesics
• Opioids are not the only ‘magic bullets’ that can target pain signal transmission. The ‘adjuvants’ are
now shown to work via other neuronal and synaptic receptors and ion channels, and may now be
as important as opioids.
• Voltage-gated calcium channels can be blocked by gabapentin or pregabalin (Woolf, 1999).
• Sodium channels, which in turn activate calcium channels, can be blocked by local anaesthetics
and older generation anti-epileptics such as carbamazepine (Dickinson, 2002). Lignocaine patches
have been successfully used in the management of focal neuropathic pain, and are particularly
eective in the symptomatic relief of allodynia and hyperpathia (Davies, 2004).

• Other drugs work by modulating noradrenergic and serotonergic transmission and re-uptake, such
as tricyclic antidepressants, SNRIs (Sindrup, 2005) and also Tramadol (Hollingshead, 2006).
• NSAIDs and COX inhibitors may exert antinociceptic action by dampening down not only
peripheral sensitisation of nerve endings, but also spinal synaptic transmission (McNichol, 2005).
• GABAA receptors and possibly also CB1 receptors reduce neuronal excitability, which can be
exploited therapeutically by benzodiazepines, alcohol or cannabinoids.
• In most forms of chronic pain, post-synaptic NMDA receptors are opened, which cause calcium
inux, nitric oxide induction, neuronal excitability and gene expression leading to neuronal
plasticity, central sensitisation, allodynia and hyperalgesia. Specic NMDA channel blockers such
as ketamine and the dextro-isomers of many opioids, notably methadone, can attenuate these
destructive changes.
5.3.1 Neuropathic pain in cancer patients
5.3.1.1 Incidence
• The reported incidence varies. In unselected cancer patients by history
and examination alone, incidence rates are 0.5% neuropathic and 30%
mixed (Grond,1999), while in a survey of clinicians in 24 countries, pure
neuropathic pain numbered 8% and those with “neuropathic element” 40%
(Caraceni,1999). Using Questionnaires, NPQ, LANSS, denite neuropathic
61/167 (37%), probable 37/167 (22%) (Mercadante, 2009).
5.3.1.2 Causes
• The main separation of cases is between peripheral neuropathic pain
secondary to chemotherapy and other types of cancer-related neuropathic
pain.
5.3.1.3 Treatment of neuropathic pain
• Peripheral neuropathic pain secondary to chemotherapy responds poorly to
typical antineuropathic treatments such as amitriptyline (50mg), nortriptyline
(100mg), lamotrigine (300mg) and gabapentin (2.7mg) (Kautio, 2008;
Hammack, 2002; Rao, 2008; Rao, 2007) (see chapter 11).
• For other types of cancer-related neuropathic pain there is much better
success, with a combination therapy consisting of morphine, gabapentin,
amitriptyline and steroids.
• This was illustrated by a prospective study (Mishra, 2009), in which over 800
patients with cancers of tongue, mouth and lung with symptom-based
neuropathic pain diagnoses were treated with opioids (morphine 52%) and
a range of adjuvants (amitriptyline 30%, gabapentin 30%, gabapentin and
steroids 20%, steroids alone 20%). Before treatment, 70% had VAS scores of 7
or greater, while after 6 months of treatment, 5% had VAS of 4-6, 42% had VAS
of 1-3 and 53% had VAS of 0.
43

44
5.3.1.4 Outcomes
• The best evidence is for gabapentin, with 2 open-labelled studies (Ross,
2005; Keskinbora, 2007) as well as 1 short (10 day) placebo controlled study
(Caraceni, 2004).
• The evidence for amitriptyline as an addition to opioids was not good from
one placebo controlled study, but the assessment period was 10 days after
starting treatment, which is generally thought to be too short for it to have an
eect (Mercadante, 2002).
• Other adjuvant drugs with some evidence from open-labelled studies are
Sodium Valproate as an add-on to opioids (Hardy, 2001) and Flecainide (von
Gunten, 2007).
5.4 Non-analgesics drugs in pain management
• Some painful conditions that are seen in cancer patients can be successfully managed by the use of
non-analgesic drugs.
• Bisphosphonates and Calcitonin are used in treating bone pain and hypercalcemia in metastatic
bone disease and multiple myeloma (Martinez-Zapata, 2003; Wong, 2002).
• Steroids alleviate pain due to CNS involvement, plexus or peripheral nerve compression and visceral
organ inltration.
• Muscle relaxants like Baclofen, Diazepam or Tizanidine can be used to relieve painful muscle
spasms.
• Anticholinergics are used to relieve smooth muscle spasms; Hyoscine is used to relieve intestinal
colic; and Oxybutinin is used for painful bladder spasms.
• Calcium-channel blockers like Nifedipine are used for the management of oesophageal spasms and
tenesmus (Nasrallah, 1985).
• Depending on the pathophysiology, it may therefore make good pharmacological sense to
combine analgesics.
• Rather than simply adopting the WHO approach, which treats ‘adjuvants’ as optional, there
is increasing evidence for the benet of routinely combining opioids with these other
pharmacological agents for synergistic eects, with the prospect of reduced toxicity (Gilron, 2005).
• There is even emerging evidence that combining dierent opioids (with diering receptor binding/
modulating properties) may lead to similar advantages.
• The concept of multi-drug regimens working simultaneously on dierent cellular targets is not new,
as the modern management of cancer, rheumatoid arthritis or heart failure shows.
• The medical management of pain can use non-pharmacological options, such as hypnosis or
distraction therapies, which act via the pre-frontal cortex to decrease the perception/sensation of
pain. Acupuncture may work by causing the release of endogenous opioids.

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Ahmedzai SH. Window of opportunity for pain control in the terminally ill. Lancet 2001;357:9265:1304-5.
Ahmedzai SH, Boland J. The total challenge of cancer pain in supportive and palliative care. Current Opinion in
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Ballantyne JC, LaForge KS. Opioid dependence and addiction during opioid treatment of chronic pain. Pain
2007;129(3):235-255.
Bell RF, Wislø T, Eccleston C, Kalso E. Controlled clinical trials in cancer pain. How controlled should they be? A
qualitative systematic review. British Journal of Cancer 2006;94:1559-1567.
British Pain Society Recommendations for the appropriate use of Opioids for persistent non-cancer pain. The Pain
Society 2004, London.
Clark AJ, Ahmedzai SH, Allan LG, Camacho F. Ecacy and safety of transdermal fentanyl and sustained-release
oral morphine in patients with cancer and chronic non-cancer pain. Current Medical Research Opinion
2004;20(9):1419-28.
Caraceni A, Portenoy RK. An international survey of cancer pain characteristics and syndromes. Pain
1999;82(3):263-74.
Caraceni A, Zecca E, Bonezzi C, Arcuri E, Yaya Tur R, Maltoni M, Visentin M, Gorni G, Martini C, Tirelli W, Barbieri M, De
Conno F. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain
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Daniell HW. DHEAS Deciency During Consumption of Sustained-Action Prescribed Opioids: Evidence for Opioid-
Induced Inhibition of Adrenal Androgen Production. The Journal of Pain 2006;7(12):901-907.
Daniell HW. Opioid Osteoporosis. Archives of Internal Medicine 3 2004;338.
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Davis MP. What is new in neuropathic pain? Support Care Cancer 2004;15:353-372.
Dickinson AH, Matthews EA, Suzuki R. Neurobiology of neuropathic pain: mode of action of anticonvulsants.
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Ferreira SL, Kimura M, Teixeira MJ. The WHO analgesic ladder for cancer pain control, twenty years of use. How
much pain relief does one get from using it? Supportive Care in Cancer 2006;14:1086-1093.
Finnerup NB, Otto M. McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: An evidence
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Gilron I, Bailey JM, Tu D, Holden RR. Morphine, Gabapentin, or Their Combination for Neuropathic Pain. New
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Grond S, Radbruch L, Meuser T, Sabatowski R, Loick G, Lehmann KA. Assessment and treatment of neuropathic
cancer pain following WHO guidelines. Pain 1999;79(1):15-20.
Hammack JE, Michalak JC, Loprinzi CL, Sloan JA, Novotny PJ, Soori GS, Tirona MT, Rowland KM Jr, Stella PJ, Johnson
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Hardy JR, Rees EA, Gwilliam B, Ling J, Broadley K, A’Hern R. A Phase II Study to Establish the Ecacy and Toxicity of
Sodium Valproate in Patients With Cancer-Related Neuropathic Pain. Journal of Pain and Symptom Management
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Holdcroft A, Power I. Recent developments: Management of pain. British Medical Journal 2003;326:635-639.
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Kautio AL, Haanpää M, Saarto T, Kalso E. Amitriptyline in the treatment of chemotherapy-induced neuropathic
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Keskinbora K, Pekel AF, Aydinli I. Gabapentin and an opioid combination versus opioid alone for the management
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Lauretti GR, Oliveira GM, Pereira NL. Comparison of sustained release morphine with sustained-release oxycodone
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Martell BA, O Connor PG, Kerns RD, Becker WC. Systematic Review: Opioid Treatment for Chronic Back Pain:
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Martinez-Zapata MJ, Roqué i Figuls M, Alonso-Coello P, Català E. Calcitonin for metastatic bone pain. Cochrane
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48

Chapter 6 Psychological aspects and approaches to pain
management in cancer survivors
Summary
Psychological distress increases with the intensity of cancer pain. Cancer pain is often under-reported and under-
treated for a variety of complex reasons, including a number of beliefs held by patients, families and healthcare
professionals. There is evidence that cognitive behavioural techniques that address catastrophising and promote
self-ecacy lead to improved pain management. Group format pain management programmes could contribute
to the care of cancer survivors with persistent pain.
6.1 Psychological factors
• Persistent pain can have profound and widespread eects upon a patient’s quality of life. Mobility,
physical functioning, sleep, and concentration are typically aected by pain. Unrelieved pain
can engender anxiety, a sense of helplessness and hopelessness, and is a major risk factor for
depression.
• Psychological factors are central to the experience of pain and for treatment delivered within
a biopsychosocial model, which incorporates sensory, cognitive, emotional, behavioural and
environmental factors that interact to determine how pain is experienced, expressed and managed
(Hanson, 1990). It is important to stress that psychological factors do not ‘cause’ pain directly, but
contribute to a person’s perception of pain and its eects and their response to pain (including
seeking healthcare) and treatment (Main, 2000).
• A range of psychological factors have been identied that modulate the perception of pain,
including expectancy, perceived controllability, fear and anxiety, appraisal processes, perceived self-
ecacy and contingencies of reinforcement (Turk, 1991; Main, 2000).
• The recognition of the importance of psychological, especially cognitive, factors in the experience
of pain has lead to the development of cognitive-behavioural models of pain (Turk, 1983), and
cognitive behavioural principles underlie eective interventions for adults with chronic pain
(Morley, 1999).
• How people think about their pain, and the assumptions and expectations that they hold, will aect
their experience of pain and determine their emotional and behavioural responses. For example,
believing that rest and the avoidance of physical activities is a helpful response to pain may lead
someone to withdraw from rewarding and enjoyable activities, which may in turn result in a loss of
condence and self-esteem, and ultimately depression. People who believe that an increase in pain
indicates the progression of the disease are more likely to become distressed and more focused on
pain. Cognitive behavioural approaches help to identify, evaluate and change unhelpful thoughts,
beliefs and patterns of behaviour.
• Research on psychological factors related to cancer pain has focused on two main areas:
psychological distress and strategies for coping with pain.
• Studies examining the relationship between cancer pain and psychological distress (predominately
anxiety and depression) indicate a strong correlation between pain and distress and show that
increasing pain intensity leads to greater psychological distress (Zara, 2002; Kelsen, 1995).
49

50
• Studies of pain coping strategies and their appraisal indicated that catastrophising (dwelling on
the worst possible outcome of a situation and overestimating the probability that it will occur)
is associated with increased pain, pain interference and anxiety (Bishop, 2003; Wilkie, 1991), and
suggested that cognitive-behavioural techniques that address catastrophising and promote self-
ecacy would lead to improved pain management.
• Cancer-related pain is often under-reported and under-treated. The reasons for this are complex
and still poorly understood, but they appear to be partly due to a number of beliefs held by
patients, families and healthcare professionals, including:
• fear of addiction to medication.
• concerns about tolerance (i.e. the risk of uncontrolled pain later in illness).
• concerns about side-eects.
• the belief that pain is inevitable in cancer.
• concern that pain means disease progression.
• fear of injections.
• concern that talking about pain may distract the doctor from treating the cancer.
• the belief that “good” patients do not complain about pain (Ward, 1993).
• Within the cognitive model, a person’s interpretation of the meaning of pain can inuence their
healthcare seeking behaviour and treatment adherence; for example, if a person believes that
eective analgesia may mask their pain, making it dicult to gauge whether their disease is
progressing, they may be less willing to report pain and adhere to analgesic regimens.
6.2 Psychological approaches to pain management
Personal beliefs and appraisals, emotional reactions, coping behaviours and social contextual factors are the
primary targets of psychological interventions.
6.2.1 Coping skills training
Coping skills training teaches patients cognitive and behavioural skills to manage pain, reduce distress,
enhance their perceptions of control over pain and promote an active self-management approach.
Coping skills can be broadly grouped into attention-diversion techniques and cognitive coping
strategies.
6.2.2 Attention-diversion strategies
Attention-diversion involves redirecting attention to competing external or internal stimuli, and
strategies may include relaxation training, diaphragmatic breathing, guided imagery, self-hypnosis,
mindfulness meditation and distracting thoughts and activities (Hanson, 1990). Engaging in
meaningful and stimulating activities, for example talking to friends, listening to music and going out,
can reduce awareness of pain.

6.2.3 Cognitive coping strategies
Using methods drawn from cognitive therapy, patients are taught how to identify and change
unhelpful or negative thoughts (cognitive restructuring) that contribute to psychological distress and
facilitate more adaptive coping thoughts that reduce distress and enhance other coping eorts.
6.3 Pain Management Programmes
• Pain Management Programmes (PMPs) based on cognitive and behavioural principals are the
treatment of choice for people whose persistent pain adversely aects their quality of life (The
British Pain Society, 2007).
• A PMP aims to improve the physical, psychological, emotional and social dimensions of a person’s
quality of life, working towards achieving optimal functioning and self-reliance in managing
persistent pain. Pain relief is not a primary goal, although improvements in pain have been reported
(Morley, 1999; Van Tulder, 2000; Guzman, 2001).
• PMPs consist of education and guided practice. Education includes information on on the
principles and rationales of treatment, pain physiology, the psychological aspects of pain, exercise
and improving function, and self-management of pain problems. The emphasis, however, is upon
guided practice in the use of physical, psychological and practical methods to improve quality
of life (e.g. exercise to improve tness and mobility, a gradual return to goal-dened activities,
cognitive therapeutic methods to identify and challenge appraisals, beliefs and processing biases,
relaxation and distraction techniques, and communication skills).
• PMPs are delivered by a multidisciplinary team of healthcare professionals working in an
interdisciplinary way (Turk, 1987).
Key sta include:
• A medically qualied person with a special interest in pain management (usually a pain clinic
consultant).
• A chartered clinical psychologist or BABCP registered cognitive behavioural therapist.
• A physiotherapist (state registered).
Other health professionals, such as occupational therapists, nurses and pharmacists, have skills which are
extremely useful for the delivery of PMPs.
• PMPs are delivered in a group format, since this contributes to the normalisation of the experience
of pain and maximises opportunities for learning from other members of the group. This format is
also cost eective.
• There is good evidence for the ecacy of cognitive-behavioural based PMPs (Morley, 1999; Van
Tulder, 2000; Guzman, 2001) in reducing distress and disability and improving coping, outlook and
activity levels.
51

52
• Given the increase in cancer survival rates and the incidence of chronic pain related to cancer
treatments, as well as the impact upon quality of life, the treatment approach of PMPs could
contribute to the care of cancer survivors with persistent pain (Robb, 2006). PMPs for this patient
group would need to incorporate an educational component that addresses misconceptions about
pain, concerns related to addiction and side-eects and encourages open communication about
pain between patients and health professionals in order to address issues related to willingness to
report pain and to use analgesics.
• PMPs would not, however, be appropriate for this patient group when the pain is associated with
active or progressive disease.
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Turk DC, Stieg RL. Chronic pain: the necessity of interdisciplinary communication. Clinical Journal of
Pain1987;3:163-167.
Van Tulder M, Ostelo R, Vlaeyen S, Linton S, Morley S, Assendelft W. Behavioural treatment of chronic low back
pain: a systematic review within the framework of the Cochrane Back Review Group. Spine 2000;25:2688-2699.
Ward S, Goldberg N, Miller-McCauley V, Mueller C, Nolan A. Patient related barriers to management of cancer pain.
Pain 1993;52:319-324.
Wilkie D, Keefe F. Coping strategies of patients with lung-cancer related pain. Clinical Journal of Pain 1991;7:792-
799.

Zara C, Baine N. Cancer pain and psychosocial factors: a critical review of the literature. Journal of Pain and
Symptom Management 2002;24:526-542.
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Chapter 7 Physical therapies for cancer pain
Summary
Physiotherapists and Occupational Therapists have an important role in the management of cancer pain and
have specic skills which enable them to be patient-focused and holistic. Therapists utilise strategies which aim to
improve patient functioning and quality of life, but the challenge remains to practice in an evidence-based way.
More research is needed in this eld.
7.1 Introduction
• Physiotherapists (PT) and Occupational Therapists (OT) play an important role in the management
of patients with cancer pain and encounter these patients at various stages in their ‘cancer journey’.
The rehabilitation of cancer patients is gaining increasing recognition and is now considered an
essential component in the delivery of care (NICE, 2004).
• The main aims of therapy are to relieve pain (wherever possible) and to improve function and
quality of life using treatments based on the best available evidence. Management should be
patient-centred, collaborative and restorative and should involve family and carers to ensure a
co-ordinated approach to treatment planning and goal-setting. The patient’s engagement in the
therapy partnership is vital.
• Early referral to therapies is important with palliative care patients, and also with others in order
to prevent chronicity and help anticipate future problems. With in-patients, early referral should
result in better discharge planning, which may stop bed blocking and help patients return to their
preferred place of care.
• Much can be learned from therapists who work with musculoskeletal pain, and there is a plethora
of literature examining the role of physiotherapy and occupational therapy for patients with benign
pain. Therapists working with cancer patients may nd some of these messages helpful, but must
recognise that the majority of this work has focused on non-cancer populations..
7.2 Assessment
7.2.1 Impact of cancer-related pain
• Pain can reduce strength, vitality, activity tolerance and mobility (Cancerbackup, 2005;
Gamlin, 2002). Cancer patients with pain report signicantly lower levels of performance
status than those without pain (Lin, 2003). Turk (1998) demonstrated that pain resulting
from cancer was associated with higher levels of perceived disability and a lower
degree of activity. Pain may aect a person’s ability to care for themselves, to work or
to participate in fullling activities. The experience of cancer pain may also result in
disruption to the patient’s family and to carers’ quality of life (Ferrell, 1999).
• A common response to pain is the development of ‘pain behaviours’. These include
maladaptive behaviours such as guarding the painful area, pain watching (hyper-
vigilance), developing an overly sedentary lifestyle and avoiding activities. This inactivity
can result in deconditioning, increased muscular tension and increased attention to pain.
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7.2.2 Responses to cancer-related pain
• It is essential to explore the meaning of pain to the patient and to those closest to
them. An individual’s cultural background, spiritual, religious and philosophical beliefs all
impact upon a patient’s perception and response to cancer pain.
• Thoughts and emotional responses can contribute to the intensity of the pain
experience (Bates, 1993). Anxiety, depression, fear of the future, hopelessness, negative
perceptions of personal and social competence, decreased social activity/social support
and lack of control over pain may all be important (Breitbart et al., 2004).
7.2.3 Principles of assessment
Therapy assessments must include subjective and objective evaluations and must utilise all available
information from medical notes, other members of the MDT and the patients and carers themselves.
All relevant co-morbidities need to be considered. Assessment is rarely possible after one interaction;
rather it involves an information-gathering exercise and is a continual process which guides both initial
and ongoing treatment. Optimal timing of pharmaceutical management is often required to enable
patients to participate fully in assessment.
7.2.4 Physiotherapy assessment
This will require detailed examination of physical factors (e.g. range of joint movement, muscle power,
postural changes), with recognition and appropriate management of psychological co-morbidities (e.g.
anxiety or depression). Assessment will focus on a patient’s functional ability (e.g. their ability to transfer
or mobilise). There are three components of assessment which must be considered in all patients:
• A description of the pain (including site, severity, irritability, nature).
• Responses to the pain.
• The impact of pain on the person’s life
(Strong et al., 2002).
Therapists must be aware of the dangers of placing too much attention on the correction of physical
impairments at the expense of function (Simmonds, 1999). For many cancer patients (especially those
with advanced disease), it will be more important to complete a task than to focus on the correction of
individual impairments.
7.2.5 Occupational therapy assessment
OT assessment recognises that it is usual for cancer patients to identify and focus on those tasks and
occupational roles which they are no longer able to manage or enjoy due to their pain. The OT will
listen to the patient’s narrative and begin to identify:
• aggravating, relieving factors.
• the beliefs held regarding pain.
• what the pain means to the patients, and to those around them
• how the patient is currently managing their activities in relation to their pain.

The OT will identify which activities the individual needs to do, wants to do and is expected to do by
others.
7.2.6 Evaluating outcome
It is important to utilise reliable and valid outcome measures, as well as utilising a patient’s subjective
feedback. Outcome measures for use in clinical practice must be feasible (i.e. practical, inexpensive and
easy to use), provide extra clinical information and be responsive to changes over time. A great variety
of tools are now available, but there are no published guidelines for therapists to assist in the selection
of measures.
7.2.7 Outcome measures
Both Visual Analogue Scales (VAS) and Numerical Ratings Scales (NRS) are commonly used in clinical
practice. Previous research has suggested cut-o points for mild, moderate and severe pain on an
NRS (Figure 7.1). This is useful to consider when assessing whether improvements in pain report are
clinically signicant.
Example: A drop in pain report from 9/10 to 7/10 may be less clinically signicant than a drop from
7/10 to 5/10, although the incremental change is the same.
Fig. 7.1 Mild, moderate and severe pain as represented on NRS (Serlin 1995). 0-4 mild, 5-6 moderate,
7-10 severe.
The Brief Pain Inventory (BPI) (Cleeland, 1994) is a useful clinical tool for therapists because it reports
both pain intensity and pain interference using an NRS.
It is important that the patient remains at the centre of the treatment process. A measure which can
be used to detect the impact of therapy intervention on the patient’s self-perception of occupational
performance is the Canadian Occupational Performance Measure (Baptiste, 1993). This has also been
show to empower and actively encourage patient participation in therapy interventions.
Other tools which can be used include pain drawings (often simple body charts) or descriptive
questionnaires, such as the McGill Pain Questionnaire (Melzack, 1975).
7.3 Therapy Management
• The ultimate aim is for the patient to achieve full functional potential and become autonomous in
managing the impact of pain on their daily life. There is currently a lack of evidence for the use of
therapy interventions for patients with cancer-related pain, and research is required in this eld.
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• Interventions can be classied as physical, psychosocial and lifestyle adjustment. Psychosocial
interventions are discussed fully in Chapter 6. The complimentary & alternative approaches that
may be used by therapists are discussed in Chapter 11.
7.3.1 Physical approaches
• Some of these approaches are traditionally administered by physiotherapists (e.g.
therapeutic exercise and TENS), but other HCPs may also have sucient skills in this area
(e.g. OT, clinical nurse specialists). Graded activity for a return to function is inextricably
linked with therapeutic exercise, but may traditionally be considered the domain of the
OT. When utilising these approaches, a certain amount of manual handling is required
and therapists must pay special attention to patient comfort and position at all times.
7.3.2 Therapeutic exercise
The main goal of exercise is to address the problems associated with inactivity/immobility
(specic or general) and fear of movement. The detrimental eects of immobilisation are
well documented and include muscle wasting/weakness, joint stiness, reduced motor
control, mood changes, decreased self-ecacy, reduced coping capacity and cardiovascular
deconditioning. Exercise programmes must be tailored to the individual needs of the patient
and should start cautiously, build up gradually and be within the patient’s tolerance levels.
There are now many reviews of exercise in cancer patients, some of which include guidance
on specic precautions (Douglas, 2005; Stevinson, 2004).
7.3.3 Graded and purposeful activity
Engagement in meaningful activities (which may include craft, recreation or work) has been
shown to assist patients with cancer pain to improve their self-conception and attain task
mastery (Kennett, 2000). Appropriately prescribed and graded activities can be used to
increase activity tolerance, autonomy, social integration, self-esteem and competency, and
can also decrease pain behaviours (Heck, 1997).
7.3.4 Postural re-education
Postural re-education is appropriate for patients who have altered posture or movement
secondary to pain. It is important to attempt correction of such postural abnormalities
early in rehabilitation in order to avoid further dysfunctional movement patterns. Examples
include breast cancer patients who develop chronic post-surgical pain following breast
cancer treatment (Macrae, 2001) and adopt protective postures resulting in muscle spasm
and muscle imbalances (Cheville & Tchou, 2007). In head and neck cancer patients, there is
growing evidence for the use of Progressive Resistive Exercise training to manage shoulder
dysfunction and pain secondary to spinal accessory nerve damage. The importance of
correcting posture and scapular stability prior to resistance exercise has been documented
(McNeely, 2004).
7.3.5 Massage and soft tissue mobilisation
Soft tissue mobilisation is widely practised in the management of pain and includes
techniques such as scar mobilisation/massage, myofascial techniques and connective tissue
massage. A wealth of information is available on such approaches (Hunter, 1994; Mannheim,
2001).

7.3.6 Transcutaneous Electrical Nerve Stimulation (TENS)
• TENS is a non-invasive form of electrical stimulation, which has been used for many
years to treat a wide range of pain problems. Although experts suggest that TENS has
an important role, there are currently no formal guidelines for the use of TENS in cancer
patients. Only two RCTs evaluating TENS use in cancer-related pain have been identied
(Robb, 2007; Gadsby, 1997) and the eectiveness of TENS remains inconclusive (Robb,
2008). However, some patients may nd it benecial.
• Conventional TENS is the most common mode of delivery and should be the rst
treatment option in most situations. It is generally recommended to start with TENS
electrodes in the painful area or an adjacent dermatome. The intensity should be “strong
but comfortable” and patients can safely increase treatment time up to several hours, as
long as no side-eects occur and benet continues.
7.3.7 Heat and cold therapy
The application of heat can be achieved through simple methods (e.g. a hot bath to aid
relaxation or more localised applications such as heated packs). Cold can be delivered via
ice-packs and home remedies can be devised (e.g. using frozen peas wrapped in a towel or
a protective fabric to prevent frost burn). All standard contra-indications and precautions
must be followed and the choice of treatment will depend on pain presentation and the
therapeutic eects needed.
7.4 Lifestyle Adjustment
• Typically, it is the OT who addresses this aspect of management, although the PT can
also be involved in some aspects (e.g. prescription of walking aids). An analysis of
activity tolerance levels and education in skills can enable functional restoration without
provoking painful episodes. Techniques such as pacing, planning, prioritising, energy
management, activity analysis, work simplication, time management, compensatory
techniques, ergonomic principles and the reorganisation of routines can be taught to
provide the patient with the skills necessary to restructure their lifestyle, thus minimising
painful episodes.
• Analysing, grading and adapting activities allow patients to continue managing
themselves within their ability, tolerance level and pain parameters (College of
Occupational Therapy, 2004; Strong, 2002). The restructuring of lifestyle and routine,
environmental adaptation, task simplication, fatigue management, appropriate
equipment and orthotic prescription and interventions regarding correct positioning
and pressure relief during activity facilitate independence, conserve energy, minimise
pain on exertion and enable valued activities to be continued.
References
Baptiste S, Law M, Pollock N, Polatajko H, McColl MA, Carswell A. The Canadian Occupational Performance
Measure. World Federation of Occupational Therapy Bulletin 1993;28:47-51.
Bates MS, Edwards WT, Anderson KO. Ethnocultural inuences on variation in chronic pain perception. Pain
1993;52:101-112.
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60
Breitbart W, Payne D, Passik SD. Psychological factors in pain experience. In: D. Doyle, G. Hanks, N. Cherny and K.
Calman, eds. Oxford Textbook of Palliative Medicine 3rd edition. Oxford: Oxford Press 2004:425-426.
Cancerbackup (2005). Describing pain [online] Available from:
http://cancerbackup.org.uk/resourcessupport/symptomssideeects/pain [cited 01 Nov 2006].
Cheville AL & Tchou J (2007). Barriers to rehabilitation following surgery for breast cancer. Journal of Surgical
Oncology. 95: 409-418.
Cleeland CS, Ryan KM. Pain assessment: Global use of the Brief Pain Inventory. Annals of Academy of Medicine
Singapore 1994;23(2):129-138.
College of Occupational Therapists, HOPE The Specialist Section of Occupational Therapists in HIV/AIDs, Oncology,
Palliative Care , Education. Occupational Therapy intervention in cancer: Guidance for professionals, managers and
decision makers. London: COT, 2004.
Douglas E. Exercise in cancer patients. Physical Therapy Reviews 2005;10(22):71-88.
Ferrell BR, Grant M, Borneman T, Juarez G, ter-Veer A. Family care giving in cancer pain management. Journal of
Palliative Medicine 1999;2(2):185-195.
Gadsby JG, Franks A, Jarvis P, Dewhurst F. Acupuncture-like transcutaneous electrical nerve stimulation within
palliative care. Complementary Therapies in Medicine 1997;5:13-18.
Gamlin R, Lovel T. Pain Explained; A guide for patients and carers. Rugby:Altman Publishing, 2002.
Heck SA. The eect of purposeful activity on pain tolerance. American Journal of Occupational Therapy
1987;42(9):577-581.
Hunter G. Specic soft tissue mobilization in the treatment of soft tissue lesions. Physiotherapy 1994;80:15-21.
Kennett CE. Participation in a creative arts project can foster hope in a hospice day centre. Palliative Medicine
2000;14(5):419-425.
Lin CC, Lai YL, Ward SE. Eect of cancer pain on performance status, mood states, and level of hope among
Taiwanese cancer patients. Journal of Pain and Symptom Management 2003;25(1):29-37.
Macrae WE. Chronic pain after surgery. British Journal of Anaesthesia 2001;87(1):88-98.
Mannheim CJ. The Myofascial Release Manual, 3rd edn. New Jersey: Slack Incorporated, 2001.
McNeely ML, Parliament M, Courneya CS, Seikaly H, Jha N, Scrimger R, Hanson J. A pilot study of a randomised
controlled trial to evaluate the eects of progressive resistance exercise training on shoulder dysfunction caused
by spinal accessory neurapraxia/neurectomy in head and neck cancer survivors. Head & Neck 2004;26(6):518-530.
Melzack R. The McGill pain questionnaire: major properties and scoring methods. Pain 1975;1:277-299.
National Institute for Clinical Excellence (NICE) 2004. Improving supportive and palliative care for adults with
cancer. From: www.nice.org.uk.
Robb KA, Bennett MI, Johnson MI, Simpson KJ, Oxberry SG. Transcutaneous electric nerve stimulation (TENS)
for cancer pain in adults. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD006276. DOI:
10.1002/14651858.CD006276.pub2.

Robb K, Newham D, Williams JE. Transcutaneous Electrical Nerve Stimulation vs Transcutaneous Spinal
Electroanalagesia for chronic pain associated with breast cancer treatments. Journal of Pain and Symptom
Management 2007;33(4):410-419.
Serlin C, Mendoza TR, Nakamura Y, Edwards KR, Cleeland CS. When is cancer pain mild, moderate or severe?
Grading pain severity by its interference with function. Pain 1995;61:277-284.
Simmonds M. Physical function and physical performance in patients with pain: what are the measures and
what do they mean? In: Max M, ed. Pain 1999 an updated review. Refresher course syllabus. Seattle: IASP press,
1999:127-136.Stevinson C, Lawlor DA, Fox KR. Exercise interventions for cancer patients: a systematic review of
controlled trials. Cancer Causes Control 2004;15(10):1035-1056.
Strong J, Bennett S. Cancer pain. In: J Strong, A Unruh, A Wright, G Baxter (eds) Pain. A Textbook for Therapists.
2002. Edinburgh: Churchill Livingstone.
Strong J, Sturgess J, Unruh AM, Vicenzino B. Pain assessment and measurement. In: J Strong, A Unruh, A Wright, G
Baxter (eds) Pain. A Textbook for Therapists. 2002. Edinburgh: Churchill Livingstone.
Turk DC, Sist TC, Okifuji A, Miner MF, Florio G, Harrison P, Massey J, Lema ML, Zevon MA. Adaptation to metastatic
cancer pain, regional/local cancer pain and non-cancer pain: role of psychological and behavioural factors. Pain
1998;74(2-3): 247-256.
Further reading
Chartered Society of Physiotherapy. The Role of Physiotherapy for People with Cancer: CSP Position Statement
2003. London: CSP.
Giord L,Thacker M, Jones MA. Physiotherapy and pain. In: McMahon and Koltzenburg (ed.) Wall and Melzack’s
Textbook of Pain 2005. Edinburgh: Churchill Livingstone.
Pan CX, Morrison RS, Ness J, Fugh-Berman A, Leipzig RM.Complementary and Alternative Medicine in the
management of pain, dyspnoea and nausea and vomiting near the end of life: a systematic review. Journal of Pain
and Symptom Management 2002;20(5):374-387.
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Chapter 8 Invasive procedures for cancer pain
Summary
Patient selection for an interventional procedure requires knowledge of the disease process, the prognosis, the
expectations of patient and family, a careful assessment and discussion with the referring physicians. There is
good evidence for the eectiveness of a coeliac plexus block and intrathecal drug delivery. Safety, aftercare and
the management of possible complications have to be considered in the decision-making process. Where applied
appropriately and carefully at the right time, these procedures can contribute enhanced pain relief, reduction of
medication use and a markedly improved quality of life.
8.1 Introduction
• This chapter focuses on the interventional procedures that are considered to be the most eective.
It deals with the pharmacological blockade of neural tissue by targeted injection or infusion; their
destruction by chemical, physical or surgical methods; and the xation of vertebral compression
fractures.
• For a few procedures (coeliac plexus ablation, intrathecal infusions, see below), there is controlled
trial evidence in cancer populations. For most procedures, there is less robust evidence of largely
uncontrolled case series.
• A pragmatic approach is required when deciding whether to oer such therapies. The likely
benets and possible risks need to be considered and compared with those of continuing with
pharmacological management. Typically, interventional management of cancer pain does not
substitute for other modalities, but can improve pain relief and allow for a reduction in systemic
medications and their side-eects.
• A careful assessment of the pain should be undertaken by an interdisciplinary team, usually
including specialists in pain, palliative care and nursing, although the team might include others.
Practical factors should be considered, such as the discharge home, as well as patient and family
preferences. Complex situations will often require high-level discussion (Chapter 13).
• It has been traditional to consider exhausting oral or topical analgesia before considering invasive
methods; however, this is not always in the patient’s best interests. Where there are unacceptable
side-eects from opioids, such as drowsiness, then invasive methods may be preferred; while a
pump implanted early in advanced cancer can allow for the maximum benet to be obtained.
• This chapter aims to provide information related to benets and adverse eects for interventional
procedures commonly used in cancer pain management.
8.2 Types of interventional procedures
• These most typically involve interruption to or modication of nerve conduction, with the aim of
diminishing pain from a target area. The nerves involved include those of the peripheral, autonomic
and central nervous systems.
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• The procedures may be considered to be non-destructive or destructive. In non-destructive
procedures, nerve blockade or modulation is achieved by the deposition of reversible
pharmacological agents. These may be provided by bolus injection and most commonly involve
local anaesthetic agents, often supplemented by depot steroids. Alternatively, catheter placement
allows for the continuous delivery of agents. When placement is adjacent to peripheral or
autonomic nerves, similar agents are used. For catheter placement in the spinal canal with the
aim of modulating neuronal activity of the spinal cord, dierent agents are used. These are most
commonly opioids, often supplemented by local anaesthetics and/or the alpha-2 adrenergic
agonist, clonidine. More recently, the voltage gated calcium channel blocker, ziconotide, has been
introduced (Staats, 2004).
• The destructive procedures involve the use of chemical agents (alcohol 50-100% and phenol
6-10%), physical methods of heat (radiofrequency) and cold (cryoablation) and surgery.
• Destructive procedures must only be provided by appropriately trained personnel, and are best
oered within a multidisciplinary framework of care that recognises the psychosocial components
of the pain experience. Failure to do so is likely to reduce the ecacy of such procedures.
• Patients should be thoroughly informed about any likely sensory decits and possible
complications.
• In most cases, destructive procedures should rst be simulated with a local anaesthetic to allow the
patient to experience the sensory changes that may occur (Cousins, 1998).
• The patient should be closely followed as an inpatient for several days after the destructive
procedure, with close monitoring and planned opioid reduction in order to avoid drowsiness and
respiratory depression when the respiratory stimulation of pain is removed.
8.3 Peripheral nerve blockade
• Peripheral nerve blocks have a limited role in cancer pain management. There is no controlled trial
evidence, but case series describe pain relief for a short time with the local anaesthetic blockade of
the regional nerve supply of a target area. They may therefore be useful for perioperative pain and
other acute cancer pains, such as pathological rib fracture (intercostal nerve blockade). This may be
achieved by the bolus injection of local anaesthetic. It is often supplemented with depot steroid
with the aim of providing longer term relief, but there is no evidence to support this practice for
peripheral nerves (McCarberg, 2007) . Alternatively, catheter infusions of local anaesthetic adjacent
to the brachial plexus (Vranken, 2000) or other nerves may prolong the pain relief (Cooper, 1994;
Amesbury, 1999).
• Neurolytic blockade of peripheral nerves produces short-term relief; for instance, intercostal
neurolysis has a median duration of 3 weeks (Wong, 2007). Although this study found no incidences
of neuritis, the survival time was short, and others have reported an incidence of neuritis of 30%
(Doyle, 1982). Neurolytic agents should be limited to those with a short life expectancy.
8.4 Autonomic nerve blockade
It is known that the sympathetic nervous system carries pain aerents from the viscera and that blockading these
can reduce pain.

8.4.1 Coeliac plexus ablation
• The coeliac plexus carries visceral aerents from several abdominal organs, including the
pancreas, liver biliary tract, renal pelvis ureter, spleen and bowel up to the rst part of the
transverse colon.
• The injection of a neurolytic medication around the coeliac plexus has been most
investigated for pancreatic cancer pain, but a role has been found for other upper
gastrointestinal malignancies, such as gastric cancer, oesophageal cancer, colorectal
cancer, liver metastasis, gallbladder cancer and cholangiocarcinoma (Eisenberg, 1995).
• Access to the plexus is most commonly posterior, with needle placement in front of or
posterior to the crura of the diaphragm (Weber, 1996). However, other approaches are
used such as anterior (Lieberman, 1988), endosopic (Abeldi, 2001) and transdiscal (Ina,
1996). Imaging most commonly involves uoroscopy, but some of the alternatives used
include computerised tomography (Haaga, 1984) and MRI (Hol, 2000). Whilst there is no
apparent dierence in outcome between these methods, they do allow for access in
certain individuals where brous inltration or tumour invasion may distort the anatomy
aecting neurolytic spread (Akhan, 1997; DeCicco, 2001), or may be valuable when
patients cannot lie on their front (Perello, 1999).
• In a single blind randomised controlled trial of 100 patients with pancreatic cancer,
neurolytic plexus ablation was compared with pharmacological management
combined with sham procedure. Pain relief was better in the interventional group for
6 weeks (Wong, 2004). A meta-analysis (Yan, 2007) of 5 randomised controlled trials of
coeliac plexus ablation found signicantly improved pain relief when compared with
pharmacological management or local blockade of the plexus for 8 weeks, with reduced
opioid consumption in the ablation group.
• Up to 30% of patients experience hypotension after a coeliac plexus block due to the loss
of sympathetic tone and splanchnic vasodilatation (Fugere, 1993). This reaction usually
manifests itself within the rst 12 hours. Up to 60% of patients report diarrhoea resulting
from a sympathetic blockade and unopposed parasympathetic eerent inuence after
coeliac plexus block, which usually resolves within 48 hours (Hastings,1991). Neurologic
complications, including paraplegia, leg weakness, sensory decits and paresthesias have
been reported after coeliac plexus ablation, with a large study reporting four cases of
paraplegia after 2730 coeliac plexus blocks (Davies, 1993). Paraplegia was attributed to
either direct injury of the spinal cord during the procedure or spinal infarction secondary
to spasm of the spinal artery.
• Theoretically, radiofrequency splanchnic denervation should avoid the risk of such
paraplegia (Raj, 2002), but the outcome is less studied. It may be an option when the
relative risks are discussed with the patient.
8.4.2 Superior hypogastric plexus block
• The superior hypogastric plexus carries aerent from the bladder, uterus, vagina, prostate,
testes, urethra, descending colon and rectum. Superior hypogastric block may relieve
pelvic pain and a block of these nerves has been described as reducing pain associated
with pelvic malignancy (Plancarte, 1997). The posterior approach is commonest, but an
anterior approach has been described (Kanazi, 1999).
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66
8.4.3 Ganglion impar block
• This is the most inferior sympathetic ganglion, lying anterior to the sacrococcygeal
junction. It has been shown in case series to provide pain relief for patients with
advanced cancers of the pelvis and perineum, after abdominoperineal resection for
rectal cancer (Plancarte,1997) and following radiation proctitis (Rabah, 2001).
8.5 Neuraxial blocks
• Neuraxial blocks may be epidural (outside the theca or dura mater) or intrathecal (into the
cerebrospinal uid).
• Epidural local anaesthetic and steroid can provide temporary pain relief where a vertebral
metastasis is associated with nerve compression.
• Care should be exercised if an impending cord compression or an invasion of the epidural canal by
a tumour is suspected, and imaging may be advisable in such circumstances.
• Despite the lack of evidence to support these interventions, several experienced practitioners have
used and continue to use these techniques with reported benet to patients. Epidurals with steroid
and local anaesthetic can provide temporary pain relief.
8.5.1 Intrathecal and spinal nerve root neurolysis
• A saddle block with heavy intrathecal phenol can be used for perineal pain of somatic
origin in advanced pelvic cancers, especially where bladder and bowel function are
already compromised.
• Chemical neurolysis of spinal nerve roots is used less frequently than in the past, since
safer interventions (e.g. neuraxial infusions) have been developed. Whilst there are case
series describing the eective relief of pain, the duration is limited and the incidence of
neurological decits is high (Lynch, 1992).
8.6 Neuraxial infusions
• Some patients with advanced cancer may have pain which cannot be controlled with systemic
medications, or the use of these medications may be limited by unacceptable side-eects at doses
below those required to give adequate relief. For these patients, the administration of drugs by
the spinal route, either epidurally or intrathecally, may be required and gives good control in the
majority of cases (Baker, 2004).
• There are dierent types of procedures, ranging from percutaneous lines to fully implanted
programmable pumps. The fully implanted systems carry less risk of infection and have lower
maintenance, but the operation is more prolonged (Williams, 2000). The costs of the therapy
currently suggest that implanted systems are more cost eective than the percutaneous after 3
months (Mueller-Schwefe, 1999).
• There is evidence from randomised controlled trials of improved pain relief and less drug-related
side-eects compared with medical therapy for fully implanted systems. The reversal of drowsiness
associated with systemic opioids is of great practical signicance (Smith, 2002, 2005; Staats, 2004).

• These procedures carry a moderate level of minor adverse eects and a low level of serious
adverse eects (Williams, 2000). They should be reserved for those patients whose pain cannot be
controlled with systemic analgesia and undertaken in centres experienced with the techniques and
with aftercare (British Pain Society, 2008).
• The most eective drugs are opioids, commonly morphine, and generally patients who respond
to spinal morphine are those who only partially respond to systemic morphine and/or are limited
by dose-related side-eects.. Patients who are unresponsive to large doses of systemic opiods are
unlikely to respond to spinal opioids. Other drugs that appear to be eective spinally include local
anaesthetics (typically bupivacaine) (Van Dongen, 1999), alpha-2 agonists (clonidine) (Eisenach,
1996) and ziconotide (Staats, 2004). In a randomised placebo controlled study of Zicomotide in ill
patients, 50% on active therapy vs 17% on placebo achieved greater than 30% pain relief. However,
30% on ziconotide against 10% on placebo experienced “serious” side-eects, while 38% of those
on ziconotide discontinued treatment and follow-up was generally thought to be too short. Fuller
details of the use of intrathecal therapies can be found elsewhere (British Pain Society, 2008).
• Intraventricular opioids can be administered via an implanted pump and catheter for pain in
the head and face. Cerebrospinal uid diversion via a shunt or third ventriculostomy may be
appropriate for palliation in some cases of obstructive hydrocephalus that are otherwise inoperable;
craniotomy and subtotal removal of a malignant cerebral tumour is a routine neurosurgical
palliative procedure.
8.7 Domiciliary Management of Spinal Catheters
Most patients want to die at home (Higginson, 1998), and while the safe management of spinal drug infusions
does present challenges to this, these can be overcome to facilitate this aim (Gestin, 1997). In addition, with
percutaneous drug delivery, intrathecal use allows lower dosage and therefore longer intervals between infusion
relling of ambulatory pumps, facilitating home care and reducing the risk of infection. Intrathecal catheters may
be less prone to dislodgement and blockage due to brosis (Crul, 1991), and have been shown to be safer in the
domiciliary setting (Nitescu, 1990).
8.7.1 Preparation
• Full involvement of the primary care team in the management of pain is vital. If, when
considering the use of spinal drug delivery, management at home is identied as a
priority, it is essential to establish that the patient and family are suitable and have
appropriate goals and expectations. The community nursing and primary care teams
should be happy to co-operate and be involved.
• Psychological assessment should be considered once pain has been relieved and
sedation due to analgesics minimised, since some patients may be less distracted from
the other psychological aspects of their illness. This can lead to diculties with good
symptom control. Full discussion and consent from the patient and family, taking factors
such as these into consideration, is essential.
8.7.2 Procedure
• Percutaneous catheters, injection portals or fully implanted systems may be used, but a
factor in patient selection is the shorter expectation of survival in this group compared
with patients with non-malignant pain. Percutaneous catheters may be tunnelled or
non-tunnelled; tunnelled catheters are less prone to displacement and infection (Baker,
2004).
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• Implantation and other procedures are ideally undertaken in a sterile facility with
resuscitation facilities in a hospital or hospice. Insertion as a domiciliary procedure has
been reported (Mercadante, 1994), but this does raise issues with sterility and the ability
to resuscitate in the event of side-eects.
• Very compact and reliable battery-powered infusion pumps are available that allow both
continuous and patient-controlled bolus drug administration.
8.7.3 Aftercare
• It is imperative that those who will be involved in the patient’s management at home
are fully trained and condent in the necessary techniques and knowledge before
discharge. The patient’s management should also be stabilised as an inpatient or
in a hospice prior to discharge home, with titration down of systemic analgesics to
avoid opioid overdosage in particular (SIGN, 2000). The co-operation of the patient’s
general practitioner and out-of-hours service is important, and this is supported by
the availability of detailed guidelines or protocols and back-up from members of the
specialist pain or palliative care team is essential (British Pain Society, 2008). This should
be recognised in job plans.
• With appropriate training and compliance with competencies, the relling of infusion
reservoirs can be performed by community nursing sta, as well as monitoring of the
patient’s condition, particularly pain relief, temperature and the state of implantation
sites. Again, guidelines or protocols should support this.
8.10 Anterolateral cordotomy
• This can be undertaken as a percutaneous or open procedure, involving intervention on the side of
the spinal cord opposite to that of the pain to ablate the spinothalamic tract bres. Consequently, it
reduces the sensation of touch and temperature in addition to pain.
• The awake percutaneous procedure ablates the spinothalamic tract using radiofrequency
lesioning through a needle inserted between the rst and second cervical vertebrae. Its value
in mesothelioma is well documented (Jackson, 1999), and its use in other lateralised pains is
recognised (Crul, 2005).
• Immediate pain relief is achieved in the majority, with 80% either stopping or reducing opioids;
but pain recurs in a third of these after six to twelve months (Jackson, 1999). The main risk is of
weakness of the leg contralateral to the side of the pain through damage to the corticospinal tract;
mild eects are seen in up to 8-10% in the rst few days, but prolonged eects are reported in only
1-2% (Crul, 2005). This risk increases, for topographical reasons, when the lower sacral dermatomes
are targeted. Painful dysaethesias occur in about 5% of cases (Jackson, 1999).
• While percutaneous cordotomy can only be performed in the cervical area, the spinothalamic
bres can be divided by open operation in the thoracic cord. This avoids the risk to respiration and
to the upper limb when the pain is below the waist (e.g. secondary to invasion of the lumbosacral
plexus and is recommended for bilateral procedures to avoid fatal sleep apnoea). In a small series
(Jones, 2003), no patients experienced motor weakness and all had complete or nearly complete
and sustained relief of the target pain, allowing a substantial reduction in medication for all but
one. This released them from being closely tied to the hospital/hospice, allowing greater freedom
and independence, which was dramatic in some cases (e.g. holidays abroad). There were no new
sphincter disturbances reported.

8.9 Midline myelotomy.
• Splitting the spinal cord in the midline posteriorly was intended to divide the spinothalamic
bres as they crossed, thereby controlling bilateral pain while simultaneously avoiding the risks of
bilateral cordotomy. Introduced in 1926, it was not particularly successful until the serendipitous
observation in 1970 that a single level myelotomy at C1 produced analgesia over a wide body area.
It was subsequently found that a limited midline myelotomy at T10 was eective against pelvic
visceral cancer pain (Gildenberg, 1991). The recent discovery of a specic pathway in the medial
dorsal columns, which conduct visceral pain (Hirschberg, 1996), provides a possible substrate for
this operation which appears to be very eective and safe (Nauta, 2000), but is rarely used.
8.10 Other neurosurgical procedures
In the past, many surgical targets in the brain have been tried with varying degrees of success and morbidity,
but none is now used more than sporadically. They include sites in the medulla, pons, midbrain, thalamus and
hypothalamus, as well as the somatosensory and cingulate cortices. The pituitary gland provided one of the most
useful targets; transnasal alcohol-induced hypophysectomy was very eective against hormone-dependant and
diuse cancer pain, particularly when this resulted from bone metastases from breast and prostate. Diabetes
insipidus occurred in half the patients and visual disturbances were common; pharmacological hormonal
manipulation has made this redundant. Dorsal root entry zone (DREZ) lesions are rarely used for cancer pain.
An extensive laminectomy is required, the morbidity is relatively high, only paroxysmal pain responds well and
cordotomy or rhizotomy are likely to be preferable.
8.11 Vertebroplasty
Painful pathological fractures of vertebra that do not respond to the conservative therapies of medications,
TENS or steroid epidurals can be considered for xation by cemented vertebroplasty. Open studies in myeloma
and metaststic cancers report pain relief that is often complete in around 80% of patients (Gangi, 1999; Fourney,
2003; Dudeney, 2002). Cement leak is the commonest risk at around 5%, and complications from this are rare but
serious (Hentschel, 2005).
References
Abeldi M, Zfass A. Endoscopic ultrasound-guided neurolytic celiac plexus block. Journal of Clinical
Gastroenterology 2001;32:390 -393.
Akhan O, Altinok D, Özmen MN, Oguzkurt L, Besim A. Correlation between the grade of tumoral invasion and pain
relief in patients with celiac ganglia block. American Journal of Roentgenology 1997;168:1565 -1567.
Amesbury B, O’Riordan J. The use of interpleural analgesia using bupivacaine for pain relief in advanced cancer.
Palliative Medicine 1999;13(2):153-158.
Baker L, Lee M, Regnard C, Crack L, Callin S. Evolving spinal analgesia practice in palliative care. Palliative Medicine
2004;18:507-515.
British Pain Society. Intrathecal drug delivery for the management of pain and spasticity in adults;
recommendations for best clinical practice. British Pain Society 2008. ISBN 978-0-9551546-3-8.
Cooper MG, Keneally JP, Kinchington D. Continuous brachial plexus neural blockade in a child with intractable
cancer pain. Journal of Pain and Symptom Management 1994;9(4):277-81.
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Cousins MJ, Bridenbaugh PO. Neural Blockade in Clinical Anesthesia and Management, 3rd ed. 1998. Lippincott-
Raven 1998: New York.
Crul BJ, Delhaas EM. Technical complications during long-term subarachnoid or epidural administration of
morphine in terminally ill cancer patients: a review of 140 cases. Regional Anesthesia and Pain Medicine
1991;16(4):209-13.
Crul BJP, Blok LM, Van Egmond J, Van Dongen RTM. The present role of percutaneous cervical cordotomy for the
treatment of cancer pain. The Journal of Headache and Pain 2005;6(1):24-29.
Davies DD. Incidence of major complications of neurolytic celiac plexus block. Journal of the Royal Society of
Medicine 1993;86:264-266.
DeCicco M, Matovic M, Bortolussi R. Celiac plexus block: injectate spread and pain relief in patients with regional
anatomic distortions. Anesthesiology 2001;94:561-565.
Doyle D. Nerve blocks in advanced cancer. Practitioner 1982; 226(1365):539, 541-4.
Dudeney S, Lieberman IH, Reinhardt MK, Hussein M. Kyphoplasty in the treatment of osteolytic vertebral
compression fractures as a result of multiple myeloma. Journal of Clinical Oncology 2002;20(9):2382-2387.
Eisenach, JC, De Kock M, Klimscha W. Alpha sub 2-Andrenergic Agonists for Regional Anesthesia: A Clinical Review
of Clonidine (1984 -1995). Anesthesiology 1996;85:655-74.
Eisenberg E, Carr DB, Chalmers TC. Neurolytic coeliac plexus block for treatment of cancer pain: a meta-analysis.
Anesthesia Analgesia 1995; 80:290-295.
Fourney DR, Schomer DF, Nader R, Chlan-Fourney J, Suki D, Rhines LD, Ahrar K, Gokaslan ZL. Percutaneous
vertebroplasty and kyphoplasty for painful vertebral body fractures in cancer patients. Journal of Neurosurgery
2003;98(1):21-30.
Fugere F, Lewis G. Coeliac plexus block for chronic pain syndromes. Canadian Journal of Anaesthesiology
1993;40:954-963.
Gangi A, Dietemann JL, Guth S, Steib JP, Roy C. Computed tomography and uoroscopy-guided vertebroplasty:
results and complications in 187 patients. Seminars In interventional Radiology 1999;16(2):137-141.
Gestin Y, Vainio A, Pegurier A. Long-term intrathecal infusion of morphine in the home care of patients with
advanced cancer. Acta Anaesthesiologica Scandinavica 1997;41(1):12-17.
Gildenberg PL and Tasker RR (eds). Textbook of Stereotactic and Functional Neurosurgery. Section 17: Cancer Pain
1998. New York, McGraw-Hill, 1345-1482.
Gildenberg PL. Myelotomy through the years. Stereotactic and Functional Neurosurgery 1991;77:169-171.
Haaga JR, Kori SH, Eastwood DW, Borkowski GP. Improved technique for CT-guided celiac ganglia block. American
Journal of Roentgenology 1984;142:1201-1204.
Hastings R, McKay W. Treatment of benign chronic abdominal pain with neurolytic celiac plexus block.
Anesthesiology 1991;75:156 -158.

Hentschel SJ, Burton AW, Fourney DR, Rhines LD, Mendel E. Percutaneous vertebroplasty and kyphoplasty
performed at a cancer center: refuting proposed contraindications. Journal of Neurosurgery - Spine 2005;2(4):436-
40.
Higginson I, Astin P, Dolan S. Where do cancer patients die? Ten year trends in the place of death of cancer
patients in England. Palliative Medicine 1998;12(5):353-63.
Hirschberg RM, Al-Chaer ED, Lawand NB, Westlund KN, Willis WD. Is there a pathway in the posterior funiculus that
signals visceral pain? Pain 1996;67(2-3):291-305.
Hol P, Kvarstein G, Viken O, Smedby O, Tonnessen T. MRI-guided celiac plexus block. Journal of Magnetic
Resonance Imaging 2000;12:562 -564.
Ina H, Kitoh T, Kobayashi M, Imai S, Ofusa Y, Goto H. New technique for the neurolytic celiac plexus block: the
transintervertebral disc approach. Anesthesiology 1996;85:212 -217.
Jackson MB, Pounder D, Price C, Matthews AW, Neville E. Percutaneous cervical cordotomy for the control of pain
in patients with pleural mesothelioma. Thorax 1999;54:238-241.
Jones B, Finlay I, Ray A, Simpson B. Is there still a role for open cordotomy in cancer pain management? Journal of
Pain and Symptom Management 2003;25:179-184.
Kanazi GE, Perkins FM, Thakur R, Dotson E. New technique for superior hypogastric plexus block. Regional
Anesthesia and Pain Medicine 1999;24(5):473-476.
Lieberman R, Nance P, Cuka D. Anterior approach to celiac plexus block during interventional biliary procedures.
Radiology 1988;167:562-564.
Lynch J, Zech D, Grond S. The role of intrathecal neurolysis in the treatment of cancer-related perianal and perineal
pain. Palliative Medicine 1992;6(2):140-145.
McCarberg BH. The Treatment of Breakthrough Pain. Pain Medicine 2007;8(1):S8-S13.
Mercadante S. Intrathecal morphine and bupivacaine in advanced cancer pain patients implanted at home.
Journal of Pain and Symptom Management 1994;9(3):201-7.
Mueller-Schwefe G, Hassenbusch SJ, Reig E. Cost Eectiveness of Intrathecal Therapy for Pain. Neuromodulation
1999;2(2):77-87.
Nauta HJ, Soukup VM, Fabian RH, Lin JT, Grady JJ, Williams CG, Campbell GA, Westlund KN, Willis WD Jr. Punctate
midline myelotomy for the relief of visceral cancer pain. Journal of Neurosurgery 2000;92(2 Suppl):125-30.
Nitescu P, Applegren L, Lindler L. Epidural versus intrathecal morphine bupivacaine: assessment of consecutive
treatments in advanced cancer pain. Journal of Pain and Symptom Management 1990;5:18-26.
Perello A, Ashford NS, Dolin SJ. Coeliac plexus block using computed tomography guidance. Palliative Medicine
1999;13(5):419-425.
Plancarte R, de Leon-Casasola OA, El-Helaly M, Allende S, Lema MJ. Neurolytic superior hypogastric plexus block
for chronic pelvic pain associated with cancer. Regional Anesthesia 1997;22:562-568.
Rabah E, Souyet H, Aguilera C, Elzo JJ. Neurolytic Block of the Ganglion Impar (Walther) in Chronic Radiation
Proctitis. Analgesia 2001;5(2):63-65.
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Raj PP, Sahinler B, Lowe M. Radiofrequency lesioning of splanchnic nerves. Pain Practice 2002;2(3):241-7.
Scottish Intercollegiate Guidelines Network. Control of pain in patients with cancer. SIGN Publication no 44. June
2000.
Smith TJ, Coyne PJ, Staats PS, Deer T, Stearns LJ, Rauck RL, Boortz-Marx RL, Buchser E, Català E, Bryce DA, Cousins M,
Pool GE. An implantable drug delivery system (IDSS) for refractory cancer pain provides sustained pain control, less
drug related toxicity and possibly better survival compared with comprehensive medical management (CMM).
Annals of Oncology 2005;16:825-833.
Smith TJ, Staats PS, Deer T, Stearns LJ, Rauck RL, Boortz-Marx RL, Buchser E, Català E, Bryce DA, Coyne PJ, Pool G E.
Implantable drug delivery systems study group. Randomised Clinical Trial of an implantable drug delivery system
compared with comprehensive medical management for refractory cancer pain; impact on pain, drug related
toxicity and survival. Journal Clinical Oncology 2002;20: 4040-9.
Staats P, Yearwood T,Wallace MS, Byas-Smith M, Fisher R, Bryce DA, Mangieri EA, Luther RR, Mayo M, McGuire D, Ellis
D, Charapata SG, Presley RW, Wallace MS. Intrathecal ziconotide in the treatment of refractory pain in patients with
cancer or AIDS. JAMA: Journal of the American Medical Association 2004;291:63-70.
Van Dongen RTM, Crul BJP, Van Egmond J. Intrathecal coadministration of bupivacaine diminishes morphine dose
progression during long-term intrathecal infusion in cancer patients. Clinical Journal of Pain 1999;15(3):166-172.
Vranken JH, Zuurmond WW, de Lange JJ. Continuous brachial plexus block as treatment for the Pancoast
syndrome. Clinical Journal of Pain 2000; 16(4):327-33.
Weber J, Brown D, Stephens D, Wong G. Celiac plexus block:retrocrural computed tomographic anatomy in
patients with and without pancreatic cancer. Regional Anesthesia 1996;5:407-413.
Williams JE, Louw G, Towlerton G. Intrathecal pumps for giving opioids in chronic pain: a systematic review. Health
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Wong FCS, Lee TW, Yuen KK, Lo SH, Sze WK, Tung SY. Intercostal nerve blockade for cancer pain: eectiveness and
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Wong GY, Schroeder DR, Carns PE, Wilson JL, Martin DP, Kinney MO, Mantilla CB, Warner DO. Eect of neurolytic
celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer: a
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Yan BM, Myers RP. Neurolytic Celiac Plexus Block for Pain Control in Unresectable Pancreatic Cancer. American
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Further reading
Kanpolat Y, Savas A, Ucar T, Torun F. CT guided percutaneous selective cordotomy for treatment of intractable pain
in patients with malignant pleural mesothelioma. Acta Neurochirurgica (Wien) 2002;144:595-599.
Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann AK, Grond S. Symptoms during cancer pain treatment
following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology. Pain
2002;93(3):247 257.

Chapter 9 Complementary therapies for cancer pain
Summary
There is a weak evidence base for the eectiveness of complementary therapies in terms of pain control, but they
may improve well-being. Safety issues are also a consideration.
9.1 Introduction
• Complementary and alternative medicine (CAM) refers to a diverse array of treatment modalities
and diagnostic techniques. It has been dened as, ‘diagnosis, treatment and/or prevention which
complements mainstream medicine by contributing to a common whole, satisfying a demand not
met by orthodoxy, or diversifying the conceptual framework of medicine’ (Ernst, 2007).
• A large proportion of cancer pain patients use CAM (Goldstein, 2005). The reasons for this include
dissatisfaction with conventional medicine, desperation, compatibility between the philosophy
of CAM and the patients’ own beliefs and the wish for more control over one’s own health (Ernst,
2008).
• CAM therapies have the potential to increase wellbeing and thus inuence pain. They are often
employed in addition to conventional treatments in palliative and supportive cancer care.
9.2 Acupuncture
This is the insertion of needles into the skin and underlying tissues for therapeutic or preventive purposes at
specic sites, known as acupuncture points.
• A systematic review identied two randomized clinical trials (RCTs) and found no compelling
evidence that acupuncture controls cancer pain (Lee, 2005), which was conrmed by other
reviewers. Subsequent RCTs did not produce convincing evidence of eectiveness. However, it is
eective in alleviating chemotherapy-related nausea and vomiting and may hence contribute to
pain control (Ernst, 2006).
9.3 Aromatherapy
This is the controlled use of plant essences, applied either to the skin through massage, added to baths or inhaled
with steaming water.
• A Cochrane systematic review concluded that aromatherapy and/or massage have benecial
short-term eects on well-being in cancer patients (Fellowes, 2004). However, it has not been
convincingly demonstrated whether it is associated with clinically relevant analgesic eects.
9.4 Herbal medicine
The medical use of preparations, which contain exclusively plant material.
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• There is no convincing evidence for any herbal medicine to suggest eectiveness for treating
cancer pain (Ernst, 2007).
9.5 Homeopathy
This is where the diluted preparations of substances are taken whose eects when administered to healthy
subjects correspond to the symptoms and clinical signs of the disorder in patients.
• A systematic review of 6 RCTs found no convincing evidence that homeopathic remedies have
analgesic eects in cancer patients (Milazzo, 2006).
9.6 Hypnotherapy
This is the induction of a trance-like state to facilitate relaxation and enhance suggestibility for treating conditions
and introduce behavioural changes.
• Studies have suggested the usefulness of hypnotherapy in palliative cancer care. A systematic
review found encouraging evidence that hypnotherapy can alleviate cancer pain (Rajasekaran,
2005). Due to the often poor methodology of the primary data, this evidence was deemed
inconclusive. Similar conclusions were reached in two systematic reviews for procedural pain in
paediatric cancer patients (Wild, 2004; Richardson, 2006).
9.7 Massage
This is the manipulation of the bodies soft tissue using various manual techniques and the application of pressure
and traction.
• Massage seems to increase well-being through the reduction of stress and anxiety levels, and thus
may contribute to pain control. The evidence for analgesic eects in cancer patients is encouraging
but not convincing (Corbin, 2005).
9.8 Music therapy
The use of receptive (passive) and/or active music therapy, most commonly based on psychoanalytical,
humanistic, cognitive behavioural or developmental theory.
• There is no convincing evidence from RCT data to suggest eectiveness for pain control in cancer
patients (Ernst, 2007).
9.9 Reexology
The use of manual pressure applied to specic areas, or zones, of the feet (and sometimes the hands or ears) that
are believed to correspond to other body areas or organs.
• A few small RCTs generated no convincing evidence that reexology improves quality of life or pain
of cancer patients (Stephenson, 2000).

9.10 Relaxation
This involves techniques for eliciting a relaxation response of the autonomic nervous system, resulting in the
normalizing of blood supply to the muscles and a decrease in oxygen consumption, heart rate, respiration and
skeletal muscle activity. Most commonly, progressive muscle relaxation is used.
• Relaxation techniques have the potential to increase well-being and thus may contribute to
controlling pain. Whether these techniques have direct analgesic eects remains, however,
unknown.
9.11 Supplements
Oral medical use of preparations of herbal or non-herbal origin.
• A systematic review of nine RCTs that tested cannabinoids concluded that they are not superior
to codeine in controlling cancer pain. As cannabinoids cause central nervous depression, their
introduction into routine care was deemed undesirable (Campbell, 2001).
9.12 Safety issues
Complementary therapies are often used because they are erroneously considered safe and harmless, which
can be dangerously misleading. Some treatments like homeopathy, massage, music therapy, reexology and
relaxation are associated with only mild and rare direct risks if administered appropriately by a trained practitioner.
Others have been associated with potentially serious risks: herbal medicines and supplements with herb-
drug interactions, toxicity and contamination, acupuncture with pneumothorax and hypnosis with negative
physiological and psychological eects. General safety issues include misdiagnosis or delayed access to eective
treatments. Self-medication is another problem due to the potential interactions with conventional cancer
treatments. In addition, patients often do not disclose their use of complementary medicines to their healthcare
provider, who needs to seek the relevant information.
References
Campbell FA, Tramer MR, Carroll D, Reynolds DJ, Moore RA, McQuay HJ. Are cannabinoids an eective and
safe treatment option in the management of pain? A qualitative systematic review. British Medical Journal
2001;323:13-16.
Corbin L. Safety and ecacy of massage therapy for patients with cancer. Cancer Control: Journal of the Mott
Cancer Center 2005;12(3):158-164.
Ernst E, Pittler M, Wider B, Boddy K. The desktop guide to complementary and alternative medicine. 2nd edition
2006. London: Elsevier/Mosby.
Ernst E, Pittler MH, Wider B, Boddy K. Complementary therapies for pain management. 2007. London: Elsevier/
Mosby.
Ernst E, Pittler MH, Wider B, Boddy K. Oxford handbook of complementary medicine. 2008. Oxford: Oxford
University Press.
Fellowes D, Barnes K, Wilkinson S. Aromatherapy and massage for symptom relief in patients with cancer. The
Cochrane Database of Systematic Reviews 2004;Issue 3. Art No.: CD002287.
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Goldstein MS, Brown ER, Ballard-Barbash R, Morgenstern H, Bastani R, Lee J. The use of complementary and
alternative medicine among Californian adults with and without cancer. Evidence-Based Complementary and
Alternative Medicine 2005;2:557-565.
Lee H, Schmidt K, Ernst E. Acupuncture for the relief of cancer-related pain - a systematic review. European Journal
of Pain 2005; 9:437-441.
Milazzo S, Russell N, Ernst E. Ecacy of homeopathic therapy in cancer treatment. European Journal of Cancer
2006;42:282-289.
Rajasekaran M, Edmonds PM, Higginson IL. Systematic review of hypnotherapy for treating symptoms in
terminally ill adult cancer patients. Palliative Medicine 2005;19:418-426.
Richardson J, Smith JE, McCall G, Pilkington K. Hypnosis for procedure-related pain and distress in pediatric cancer
patients: a systematic review of eectiveness and methodology related to hypnosis interventions. Journal of Pain
and Symptom Management 2006;31:70-84.
Stephenson NL, Weinrich SP, Tavakoli AS. The eects of foot reexology on anxiety and pain in patients with breast
and lung cancer. Oncology Nursing Forum 2000;27:67-72.
Wild M R, Espie C. The ecacy of hypnosis in the reduction of procedural pain and distress in pediatric oncology: a
systematic review. Journal of Developmental Behavioural Pediatriatrics 2004;25:207-213.

Chapter 10 Cancer pain management in the community
Summary
Patients with cancer pain spend most of their time in the community until the last month of their lives.. Overall,
cancer pain prevalence in the community in Europe is 72%. Older patients and those in care homes in particular
may have under-treated pain. Primary care teams supported by palliative care teams are best placed to initiate
and manage cancer pain therapy, but the education of patients, carers and healthcare professionals is essential to
improve outcomes.
10.1 Introduction
Managing patients with cancer pain in secondary or tertiary care settings has several advantages compared to
management in community settings (dened as the patient’s home, care homes or hospices). These advantages
include more comprehensive assessment and observation, better access to investigations and more direct
inuence on prescribing and administration of therapy.
Increasingly, however, the patient’s wishes and UK government policy advocates improved palliative care, and
therefore cancer pain management, for patients in the community. Hospice patients consistently rate pain
management as a top research priority within palliative care, above other symptoms and aspects of care (Perkins,
2008). An understanding of cancer pain management in the community is therefore important for planning
services and interventions (See also chapter 8, section 8.7 for some practical guidance on domiciliary spinal
infusions).
10.2 Epidemiology of cancer pain in the community
10.2.1 Prevalence
Systematic reviews (Hearn, 2003; van den Beuken-van Everdingen, 2007) have demonstrated that
cancer pain is common and its prevalence is related to the stage of illness:
• 48% of patients with early disease.
• 59% undergoing cancer treatment.
• 64-74% with advanced disease.
These ndings are in keeping with those in the recent European Pain in Cancer (EPIC) survey of 11
European countries, which indicated an overall pain prevalence of 72% of patients with cancer in the
community. The rate was slightly higher in the UK at 77% (Breivik, 2008).
10.2.2 Pain severity
Most research on cancer pain severity has been conducted in secondary care settings (Klepstad, 2002;
Yates, 2009). Using a 0-10 numerical rating scale, hospitalised cancer patients typically report:
• mean scores for worst pain of 4.8.
• mean score for average pain of 3.7.
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78
• worse pain intensity greater than 5 in two-thirds of patients.
There has been less research in community based patients with cancer pain. The EPIC survey invited
patients with cancer pain in the community to participate who were specically not recruited through
palliative care or pain services (Breivik, 2009). For the 617 patients from the UK:
• the mean pain intensity was 6.4 (identical to the European average).
• over 90% rated their pain greater than 5 out of 10.
• a quarter were not receiving any analgesia.
This survey suggests that community based patients have greater, not less, pain intensity than those in
secondary care and highlights the need for eective strategies in primary care.
10.2.3 Eects of age on pain and treatment
Concerns exist that older people with cancer experience less eective pain management than younger
people (Clearly, 1997; Mercadante, 2007; Delgado-Guay, 2008). Recent research suggests that when
older people with cancer are compared to a younger group:
• there is no signicant dierence in pain intensity (Viganō, 1998; Yates, 2002; Mercadante,
2006, 2008; Bennett, 2009a).
• older people with cognitive impairment report greater intensity of cancer pain than
those without (Allen, 2002).
• older people are less likely to receive adequate analgesia than younger people (Cleeland,
1994; Bernebei, 1998); but importantly, these studies only compared the category of
the analgesic prescribed for a given pain intensity, and not on the basis of whether the
analgesic therapy was eective in reducing pain.
Further research into the dierences in analgesic prescription between older and younger people has
shown that:
• older people generally require lower doses of analgesia, especially opioids, than younger
people, even when controlling for pain intensity (Vigano, 1998; Hall, 2003; Mercadante,
2006, 2008). This may be due to a physiological phenomenon, for example, impaired
analgesic metabolism and excretion.
• older people may sometimes need higher doses of analgesia: 58 older people aged over
75 years attending a German pain clinic received higher doses of opioids than those
aged under 65 years (Loick, 2000).
• older people do not experience more adverse eects, dose escalation or the need for
opioid switching than younger people (Mercadante, 2006; Loick, 2000).
• older people may have poorer attitudes and knowledge about pain and analgesia than
younger people and, therefore, are reluctant to have stronger analgesia (Yeager, 1997;
Closs, 2008).

In summary, age does not appear to impact upon pain intensity, but older age does appear to be associated with
lower doses or potency of analgesic therapy in secondary care settings. These settings include hospital or hospice
inpatient units and out-patient clinics. There is a paucity of research on community based patients with cancer
pain.
10.2.4 Time spent by patients in the community
Patients with cancer pain spend most of their time in the community. Randomised controlled trials
from Italy and Norway that have examined the impact of home-based palliative care teams (Higginson,
2003; Jørdhoy, 2000) have shown that, in the last 6 months of life:
• patients referred to such teams spend between 65% and 81% of their time at home
compared with between 65% and 70% of time in a control group.
• less time was spent at home and more time in hospital in the last month of life.
Primary care teams supported by home-based palliative care teams are therefore usually best placed to
initiate and manage cancer pain therapy for the majority of patients.
10.3 Barriers to pain management
10.3.1 Patient based barriers
Attitudes or behaviours that prevent successful pain management are referred to as barriers and can
be assessed using the Barriers Questionnaire (BQ) (Ward, 1993; Gunnarsdottir, 2002). Research suggests
that the most important of these barriers are:
• fear of consequences of analgesic use (addiction and tolerance).
• fatalism about pain.
• inadequate communication with healthcare professionals.
• some religious and cultural beliefs may also impede eective pain control (Bosch, 2002;
Peacock, 2008).
However, a UK study (Closs, 2009) which interviewed older and younger patients with cancer pain at
home highlighted that:
• knowing when to take and titrate analgesia was the most important barrier for all ages.
• older people found taking and titrating analgesia signicantly more of a barrier than
younger people.
• fear of adverse eects was an important barrier for both groups.
• fatalism and communication issues were of less importance.
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10.3.2 Role of carers
Carers and family members are important sources of support for patients with cancer pain. However,
carers can have a powerful inuence on the management of pain in an individual patient. Carers’
barriers are often similar in nature to patient barriers, but also include hesitancy to administer analgesia.
The ethnicity of carers may also inuence BQ scores.
High scores by carers on the Barriers Questionnaire have been shown to:
• more strongly predict inadequate cancer pain management than patient scores (based
on patient pain scores and level of analgesia).
• be associated with reports from carers that a patient’s pain is uncontrolled (Lin, 2000;
Letizia, 2004).
10.3.3 Healthcare professionals
The knowledge and attitudes of healthcare professionals towards cancer pain management vary. When
these have been compared directly (Furstenberg, 1998; Xue, 2007):
• nurses have been shown to have better pain assessment skills than doctors or
pharmacists.
• doctors had better knowledge of clinical therapy.
• pharmacists had most knowledge about opioid pharmacology.
• all three professional groups scored poorly in some areas.
These comparisons demonstrate the need for clinical teams rather than individuals to be involved in
managing cancer pain.
10.3.4 Place of care
Primary care or community settings include care homes (nursing or residential), and patients with
cancer pain in this context can sometimes be at a disadvantage. There is a high prevalence of daily
pain in nursing home residents with cancer, and this is often untreated, particularly in older patients
(Bernabei, 1998). Nursing homes can vary in their level of stang and the equipment (e.g. syringe
drivers) necessary for eective cancer pain management, particularly at the very end of life.
10.3.5 Access to opioids
Opioids are central to eective cancer pain management, but access to opioids in the community may
be an additional barrier faced by patients. In the United States, pharmacies in predominantly ethnic
minority areas are signicantly less likely to carry sucient opioids than in other areas (Morrison, 2000;
Green, 2005). There is no comparative data specic to the UK.

10.4 Patient-based educational interventions
10.4.1 Types of interventions
Interventions designed to improve knowledge of and attitudes towards cancer pain and analgesia
have been studied extensively. These have been a combination of:
• a brief coaching session (20–40 minutes) in which patient or carer barriers are indentied
and addressed, with advice on using analgesia.
• written material.
• and occasionally audiovisual material that patients and carers can review at home.
Some studies have examined more intensive interventions that consist of repeated coaching and
support by a nurse or researcher. Comparators in these randomised trials have included either usual
care or a placebo, such as a booklet on nutrition.
10.4.2 Evidence of eectiveness
A recent meta-analysis of 21 clinical trials (Bennett, 2009b) has shown that educational interventions for
community patients with cancer pain signicantly improve knowledge of and attitudes towards pain
and analgesia, and reduce pain intensity. Compared with control, educational interventions:
• resulted in a mean reduction of around 1 point on a 0-10 numerical rating scale for both
worst and average pain intensity.
• produced a similar eect to that seen when adding paracetamol or gabapentin to
patients already treated with opioids (Caraceni, 2004; Stockler, 2004).
Patient and carer education is therefore an important, though probably under-used, component of
successful cancer pain management.
References
Allen RS, Haley WE, Small BJ, McMillan SC. Pain reports by older hospice cancer patients and family caregivers: the
role of cognitive functioning. The Gerontologist 2002;42(4):507-514.
Bennett MI, Closs SJ, Chatwin J. Cancer pain management at home (I): do older patients experience less eective
management than younger patients? Supportive Care in Cancer 2009a;17(7):787-792.
Bennett MI, Bagnall AM, Closs SJ. How eective are patient-based educational interventions in the management
of cancer pain? Systematic review and meta-analysis. Pain 2009b; 143(3):192-9.
Bernabei R, Gambassi G, Lapane K, Landi F, Gatsonis C, Lipsitz L, Steel K, Mor V. Management of pain in elderly
patients with cancer. The Journal of the American Medical Association. 1998;279(23):1877-82.
Bosch F, Baños JE. Religious beliefs of patients and caregivers as a barrier to the pharmacological control of cancer
pain. Clinical Pharmacology and Therapeutics 2002;72(2):107-111.
Breivik H, Cherny N, Collett B, de Conno F, Filbet M, Foubert AJ, Cohen R, Dow L. Cancer-related pain: a pan-
European survey of prevalence, treatment, and patient attitudes. Annals of Oncology 2009;20(8):1420-1433.
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Caraceni A, Zecca E, Bonezzi C, Arcuri E, Yaya Tur R, Maltoni M, Visentin M, Gorni G, Martini C, Tirelli W, Barbieri M, De
Conno F. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the gabapentin cancer pain
study group. Journal of Clinical Oncology 2004;14:2909-2917.
Cleary JF, Carbone PP. Palliative medicine in the elderly. Cancer 1997;80 (1):1335-1347.
Cleeland CS, Gonin R, Hateld AK, Edmonson JH, Blum RH, Stewart JA, Pandya KJ. Pain and its treatment in
outpatients with metastatic cancer. The New England Journal of Medicine 1994; 330: 592-596.
Closs SJ, Chatwin J, Bennett MI. Cancer pain management at home (II): does age inuence attitudes towards pain
and analgesia? Supportive Care in Cancer 2009;17(7):781-6.
Delgado-Guay MO, Bruera E. Management of pain in the older person with cancer. Oncology (Williston Park)
2008;22(1):56-61.
Furstenberg CT, Ahles TA, Whedon MB, Pierce KL, Dolan M, Roberts L, Silberfarb PM. Knowledge and attitudes of
health-care providers toward cancer pain management: a comparison of physicians, nurses, and pharmacists in
the state of New Hampshire. Journal of pain and symptom management 1998;15(6):335-49.
Green CR, Ndao-Brumblay SK, West B, Washington T. Dierences in prescription opioid analgesic availability:
comparing minority and white pharmacies across Michigan. Journal of Pain 2005;6(10):689-99.
Gunnarsdottir S, Donovan HS, Serlin RC, Voge C, Ward S. Patient related barriers to pain management: the barriers
questionnaire II (BQ-II). Pain 2002;99:385-396.
Hall S, Gallagher RM, Gracely E, Knowlton C, Weschules D. The terminal cancer patient: eects of age, gender and
primary tumour site on opioid dose. Pain Medicine 2003;4(2):125-134.
Higginson IJ, Costantini M, Boni L, Orengo MA, Garrone E, Henriquet F, Bruzzi P. Eect of a palliative home care
team on hospital admissions among patients with advanced cancer. Palliative Medicine 2003;17(4):315-321.
Hearn J, Higginson IJ. Epidemiology of cancer pain: a systematic review. In: Portenoy RK, Bruera E eds. Cancer Pain.
New York, NY. Cambridge University Press. 2003
Jordhøy M, Fayers P, Saltnes T, Ahlner-Elmqvist M, Jannert M, Kaasa S. A palliative-care intervention and death at
home: a cluster randomised trial. Lancet 2000;356 (9233):888-893.
Klepstad P, Loge JH, Borchgrevink PC, Mendoza TR, Cleeland CS, Kaasa S. The Norwegian Brief Pain Inventory
Questionnaire: Translation and Validation in Cancer Pain Patients. Journal of pain and symptom management
2002;24(5):517-525.
Letizia M, Creech S, Norton E, Shanahan M, Hedges L. Barriers to caregiver administration of pain medication in
hospice care. Journal of pain and symptom management 2004;27(2):114-24.
Lin CC. Barriers to the analgesic management of cancer pain: a comparison of attitudes of Taiwanese patients and
their family caregivers. Pain 2000; 88: 7-14.
Loick G, Radbruch L, Sabatowski R, Siessegger M, Grond S, Lehmann KA. Morphine dose and side-eects:
a comparison of older and younger patients with tumor pain. Deutsche Medizinische Wochenschrift
2000;125(41):1216-21.
Mercadante S, Arcuri E. Pharmacological management of cancer pain in the elderly. Drugs & Aging 2007;24(9):761-
776.

Mercadante S, Ferrera P, Villari P, Casuccio A. Opioid escalation in patients with cancer pain: the eect of age.
Journal of pain and symptom management 2006;32(5): 413-419.
Mercadante S, Roila F, Berretto O, Labianca R, Casilini S. DOMAIN-AIOM study group. Prevalence and treatment
of cancer pain in Italian oncological wards centres: a cross-sectional survey. Supportive Care in Cancer
2008;16(11):1203-11.
Morrison RS, Wallenstein S, Natale DK, Senzel RS, Huang LL. “We don’t carry that”--failure of pharmacies in
predominantly nonwhite neighborhoods to stock opioid analgesics. The New England Journal of Medicine 2000;
342(14):1023-6.
Peacock S, Patel S. Cultural inuences on pain. Reviews in Pain (British Pain Society) 2008;1(2): 6-9.
Perkins P, Booth S, Vowler SL, Barclay S. What are patients’ priorities for palliative care research? -- a questionnaire
study. Palliative Medicine 2008;22(1):7-12.
Stockler M, Vardy J, Pillai A, Warr D. Acetaminophen (paracetamol) improves pain and well-being in people with
advanced cancer already receiving a strong opioid regimen: a randomized, double-blind, placebo controlled
cross-over trial. Journal of Clinical Oncology 2004;22(16):3389-94.
van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of
pain in patients with cancer: a systematic review of the past 40 years. Annals of Oncology 2007; 18(9):1437-49.
Viganó A, Bruera E, Suarez-Almazor ME. Age, pain intensity and opioid dose in patients with advanced cancer.
Cancer 1998;83(6):1244-1250.
Ward SE, Goldberg N, Miller-McCauley V, Mueller C, Nolan A, Pawlik-Plank D, Robbins A, Stormoren D, Weissman
DE. Patient related barriers to management of cancer pain. Pain 1993;52:319-324.
Xue Y, Schulman-Green D, Czaplinski C, Harris D, McCorkle R. Pain attitudes and knowledge among RNs,
pharmacists, and physicians on an inpatient oncology service. Clinical Journal of Oncology Nursing
2007;11(5):687-95.
Yates PM, Edwards HE, Nash RE, Walsh AM, Fentiman BJ, Skerman HM, McDowell JK, Nainman JM. Barriers to
eective cancer pain management: a survey of hospitalised cancer patients in Australia. Journal of Pain and
Symptom Management 2002;23(5):393-405.
Yeager KA, Miaskowski C, Dibble S, Wallhagan M. Dierences in pain knowledge in cancer patients with and
without pain. Cancer Practice 1997;5(1):39-45.
Further reading:
The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust (2008). Breaking Barriers:
management of cancer-related pain. The Interactive Unit, The Institute of Cancer Research: Sutton.
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Chapter 11 Pain related to cancer treatments
Summary
Chemotherapy, surgery and radiotherapy are cancer treatments that can cause persistent pain in cancer survivors,
up to 50% of whom may experience persistent pain that adversely aects their quality of life. Awareness of
this problem may lead to preventative strategies, but, at the moment, treatment is symptom-based and often
inadequate.
11.1 Introduction
• Chemotherapy, surgery and radiotherapy are cancer treatments that can cause persistent pain in
cancer survivor patients and adversely aect quality of life and function.
• Up to 50% of cancer survivors may experience chronic pain secondary to treatment, yet this is
under-recognised and under-reported (Burton, 2007). Pain in cancer survivors has an additional
burden in that it is often perceived to be indicative of disease recurrence.
11.2 Painful chemotherapy-induced peripheral neuropathy (CIPN)
Neurotoxicity is a dose-limiting side-eect of many chemotherapies and biological therapies (also known as
biological response modiers, which modulate the natural response to tumour cells) used in the treatment of
cancer. Peripheral neuropathy is the most prevalent form of neurotoxicity.
11.2.1 Risk factors for the development of CIPN
• Longer duration of therapy.
• High cumulative dose.
• Type of chemotherapeutic agent (e.g vincristine, cisplatin, paclitaxel).
• Pre-existing neuropathy (including CIPN).
11.2.2 Common features of CIPN (Hausheer, 2006)
• Symmetrical symptoms.
• Length dependency: ‘stocking-glove’ distribution, distal limb long nerves aected.
• Signs and symptoms of neurosensory dysfunction.
• Onset related to the administration of neurotoxic therapy: Rapid, delayed or even after
therapy has nished.
• Relative sparing of motor function.
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86
In addition to interference with microtubular mediated axonal transport and anatomical damage, alterations in
nerve function mediated by pro-inammatory cytokines, immune cells and mitochondria have been postulated
as important in CIPN (Flatters, 2006; Cata, 2006). Pain is not synonymous with neuropathy, but is associated with
higher grades of peripheral neuropathy.
11.3 Assessment
• Several assessment tools have been used and validated (Quastho, 2002). Many are clinician rather
than patient-based, and do not all include assessment of pain, function and quality of life. A specic
CIPN pain scale could reduce under-reporting and therefore under-treating of CIPN pain.
• Quantitative sensory testing (QST) does not always reect symptoms or correlate with
chemotherapy dose, nor does it identify neuropathy earlier than clinical history and examination
(Hausheer, 2006). However, QST is an objective assessment that is useful for the surveillance of
recovery.
11.3.1 Neuropathies associated with specic chemotherapies and biological therapies
Chemotherapy Type of neuropathy
(incidence)
Onset time (coasting) Duration/recovery Other dierences
Cisplatin (carboplatin) Chronic c. 1 month (+) Some resolution in 80% over
months/years
Carboplatin less CIPN
Oxaliplatin (Cersosimo,
2005)
Acute (90%) and chronic Acute: hours Chronic: c. 1
month (+)
Acute: Chronic: as cisplatin Acute pain in up to 90%,
cold induced
Vincristine (Quastho, 2002)
(vinblastine)
Chronic (30% severe) Peak 2-3 weeks (+) Some recovery 1-3 months,
longer recovery into years
Paraesthesias common,
vinblastine less CIPN
Paclitaxel (docetaxel)
(Hausheer, 2006)
Chronic Within days (+) @6/12 19% complete
recovery, 25% no recovery
(Verstappen, 2003)
More CIPN with more
frequent dosing; docetaxel
less CIPN
Bortezomib (Velcade®)
(Richardson, 2006)
Chronic (35%) At 2y 71% some recovery High incidence of
neuropathy before starting
bortezomib
Thalidomide Chronic Any time (+) Recovery less likely
(Richardson, 2006)
No cumulative dose
response, daily dose
11.4 Prevention and treatment
• The modication and renement of chemotherapy dosage schedules (especially in a palliative
setting) can reduce CIPN. Specic preventative treatments such as amifostine, glutathione, N acetyl
carnitine, N acetyl cysteine and glutamine/glutamate have been studied in humans and animal
models with variable success. Vitamin E can reduce cisplatin and paclitaxel-induced neuropathy
(Argyriou, 2005, 2006). More research is needed to ascertain eective agents without appreciable
side-eects or aecting anticancer ecacy.
• Supportive education and non-pharmacological treatments are important. Simple strategies to
reduce the impact of numb and painful hands and feet are important, such as reducing water
temperature and using aids to help holding cups and utensils. Psychological support, physiotherapy
and occupational therapies are part of a multidisciplinary approach.

• There is little data on eective pharmacological treatments of CIPN. Current management is
predominantly based on evidence from other neuropathic pain. Although gabapentin was eective
in an animal model of CIPN (Xiao, 2007), it had no eect in humans in a controlled, randomised
crossover trial (Wong, 2005). Until there is more data, current neuropathic pain treatment guidelines
may be used (Attal, 2006; Finnerup, 2005; Dworkin, 2007). However, the mechanisms of CIPN may
be dierent to other neuropathic pain and more research is needed.
11.5 Post-cancer surgical pain
Pain syndromes after cancer surgery have been found following breast, thoracic head and neck surgery.
11.5.1 Post-breast cancer surgery pain (PBCSP)
• Chronic pain following surgery for breast cancer has been reported, with an incidence of
over 50%. Similar to other pain in cancer survivors, it is under-reported, under-recognised
and under-treated. Classication is varied and potentially confusing, yet PBCSP is likely
to be predominantly neuropathic in origin, secondary to surgical damage. Pain can
occur in the scar, arm, chest wall or the breast and is commonly associated with sensory
disturbance. Pain often interferes with function and quality of life.
11.5.1.1 Risk factors
Various risk factors predicting the development of PBCSP have been suggested, although
the data is conicting, including: young age (although this may be linked with more
aggressive disease and treatment), previous chemotherapy and radiotherapy, poorly
controlled post-operative pain, pre-existing anxiety and depression and surgical factors.
11.5.1.2 Surgical factors
• Damage and dysfunction of the intercostobrachial nerve has been proposed
as the main mechanism for PBSCP. Some studies showed lower incidence
of pain after preservation of the nerve. Thirty percent still develop pain after
preservation, while 30% do not develop PBCSP after the nerve is cut. Pain is
less common after sentinel node biopsy when compared to axillary dissection
(Barranger, 2005).
• Surgical factors are inuenced by their impact on post-operative pain. Certain
studies found that breast conserving surgery led to less chronic pain than
more radical surgery, but others have suggested the opposite (Tasmuth, 1995;
Fassoulaki, 2001).
• Reconstructive surgery may be an additional risk factor; however, few studies
have examined the more contemporaneous free ap techniques such as the
deep inferior epigastric perforator aps (DIEPs). Post-operative pain following
DIEP ap is less than after latissimus dorsi ap, and therefore putatively
associated with less chronic pain.
11.5.1.3 Treatment and prevention
• The reduction of risk factors for the development of PBSCP, such as attention
to good post-operative pain control, the careful choice of surgical procedure
and meticulous technique, could reduce PBSCP.
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• A few small trials of treatments for PBSCP have demonstrated modest and
variable benets from capsaicin and EMLA cream, gabapentin, amitriptyline
and venlafaxine. Nevertheless, treatment includes best practice for general
neuropathic pain management in a multidisciplinary approach.
11.5.2 Post-thoracotomy pain
• Persistent pain following thoracotomy for malignant and non-malignant indications may
occur in more than 50% of patients (Maguire, 2006) and, as for other types of chronic
post-operative pain, may be related to perioperative nerve damage (Perkins, 2000).
Similarly, post-operative pain is a risk factor for chronic pain. Video-assisted thoracoscopic
lung surgery (VATS) is associated with a lower incidence of persistent pain.
11.5.3 Post-head and neck surgery pain
• Surgery, in addition to chemotherapy and radiotherapy, is associated with chronic long-
term pain for patients with head and neck cancer. Pain can occur in the oral cavity, face,
neck or shoulder. The incidence of chronic pain after surgery is similar to other post-
cancer surgery pain, about 40% at 1 year and 15% at 5 years (Burton, 2007). Of the 33%
of patients who had pain 1 year after neck dissection, most had features of neuropathic
pain (van Wilgen, 2004). Treatment depends on careful assessment, providing
information to patients and a combination of physical and pharmacological approaches.
11.6 Radiotherapy-induced pain
Radiotherapy is used as a primary adjunctive treatment for many types of cancer. Certain tissues such as skin,
mucous membranes and nerves are more susceptible to damage.
11.6.1 Radiation-induced brachial plexus neuropathy (BPN)
Radiation-induced BPN was associated with breast conservation strategies and the deep delivery
of radiotherapy in the 1960s and 70s. Modication of radiotherapy treatments have reduced the
incidence of BPN (Galecki, 2006; Olsen, 1993). BPN usually occurs at least 6 months after therapy,
although higher doses may have a reduced latency. The major dierential diagnosis is tumour-related
plexopathy. In addition to clinical factors, MRI may aid diagnosis.
11.6.1.2 Features suggestive of radiation-induced neuropathy:
• Progressive forelimb weakness (upper or lower arm, depending on which
roots are involved).
• Pain less common.
• Initial involvement of upper plexus divisions.
• Slow progression and long duration.
• Incidence increases with time.

11.6.1.3 Treatment
There are no standard treatments for radiation-induced BPN, but opioids may be benecial
(Fathers, 2002). Other non-pharmacological treatments such as chemical sympathectomy
have been used, but evidence for these is limited. Current therapies are also based upon
existing treatments for other neuropathic pain.
11.6.2 Pelvic pain after radiotherapy
Radiotherapy for pelvis malignancy can also lead to radiation-induced chronic pain syndromes. Pain
results from multiple mechanisms, including eects on the gut, nerves and pelvic and hip fractures.
Dysuria may occur in 20% of patients 1 year after pelvic radiation (Burton, 2007). In one study, nearly
50% of patients reported pain in back and lower extremities, and this pain was poorly controlled with
analgesics and had a negative inuence on quality of life (Bye, 2000). Treatment is symptom-based
although, as for BPN, preventative strategies are being explored.
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Richardson PG, Briemberg H, Jagannath S, Wen PY, Barlogie B, Berenson J, et al. Journal of clinical oncology 2006;
Jul 1;24(19):3113-20.
Tasmuth T, von Smitten K, Hietanen P, Kataja M, Kalso E. Pain and other symptoms after dierent treatment
modalities of breast cancer. Annals of Oncology 1995;6:453–459.
van Wilgen CP, Dijkstra PU, van der Laan BF, Plukker JT, Roodenburg JL. Morbidity of the neck after head and neck
cancer therapy. Head Neck 2004;26:785-91.
Verstappen CC, Postma TJ, Hoekman K, Heimans JJ. Peripheral neuropathy due to therapy with paclitaxel,
gemcitabine, and cisplatin in patients with advanced ovarian cancer. Journal of Neuro-oncology 2003;63:201-5.
Wong GY, Michalak JC, Sloan JA, Lorprinzi CL. A phase III, double blinded, placebo controlled randomised trial of
gabapentin in patients with chemotherapy-induced peripheral neuropathy. A North Central Cancer Group Study.
Journal of Clinical Oncology 2005; 23(729s), Abstract 8001.
Xiao W, Boroujerdi A, Bennett GJ, Luo ZD. Chemotherapy-evoked painful peripheral neuropathy: Analgesic eects
of gabapentin and eects on expression of the alpha-2-delta type-1 calcium channel subunit. Neuroscience
2007;144:714-20.
Further reading
Singhal S, Siegel DS, Irwin D, Schuster M, Srkalovic G, Alexanian R, Rajkumar SV, Limentani S, Alsina M, Orlowski
RZ, Najarian K, Esseltine D, Anderson KC, Amato AA. Frequency, characteristics, and reversibility of peripheral
neuropathy during treatment of advanced multiple myeloma with bortezomib. Journal of Clinical Oncology
2006;24:3113-20.

Chapter 12 Management of acute pain in cancer patients
Summary
The management of acute pain, especially post-operative pain, in patients on high-dose opioids is a challenge
that requires in-depth knowledge of pharmacokinetics and the formulation of a careful management plan in
order to avoid withdrawal symptoms and inadequate pain management.
12.1 Introduction
Patients with cancer who present for surgery on high-dose opioids are a heterogeneous group with a number
of complex perioperative analgesic management problems. The main issues include: physical dependence and
the precipitation of withdrawal symptoms if insucient post-operative opioid is prescribed; and tolerance to the
eect of post-operative opioids. Additionally, there may be diculties in calculating dosage conversions between
dierent types of opioid and dierent routes of administration.
12.2 Tolerance
• Tolerance is a phenomenon in which exposure to a drug results in the diminution of an eect or
the need for a higher dose in order to maintain an eect. This may develop 1-2 weeks or more after
the initiation of opioid therapy. A larger dosage of opioid will be required to achieve the desired
eect. Short-acting opioids should be titrated to eect in a controlled, monitored environment.
• Tolerance also develops to some of the side-eects of opioids, making patients less likely to suer
from respiratory depression, itching and nausea than opioid naïve patients (See chapter 2).
12.3 Acute pain management
The management of pain in this population of patients is of increasing importance as the cancer survivor
population grows and as a greater number of patients are using convenient, sustained-release opioid
preparations and transdermal delivery systems.
• In general, the issues of physical dependence withdrawal and tolerance only relate to patients who
have been on WHO Step 3 strong opioids such as Morphine or Oxycodone for more than 1-2 weeks
preoperatively. These issues are not likely to be a problem in patients taking WHO Step 2 analgesics
such as Codeine or Tramadol unless the patient is taking larger than normal doses.
• It is common to underestimate and under-treat pain in opioid dependent patients because most
post-operative analgesic regimes are based on the opioid-naïve patient. Opioid dependent patients
should be identied preoperatively and a perioperative analgesic plan should be devised after
discussions with the patient’s opioid prescriber and with the pain team. The aim is to achieve
eective analgesia without the precipitation of withdrawal phenomena.
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12.3.1 Opioid management
Management involves the regular provision of the pre-existing opioid, supplemented with
an additional short-acting opioid, local anaesthetic, non steroidal anti-inammatory drug and
paracetamol. Patient controlled analgesia with a short lock-out and a higher bolus dose may be useful.
Neuraxial and regional analgesia is recommended where appropriate.
• Patients will present for surgery having been on many dierent types of opioid for
varying periods of time (e.g. Morphine, Oxycodone, Methadone, Hydromorphone,
Pethidine, etc.), which may have modied release (e.g. MST, Fentanyl patch) or immediate
release preparations (e.g. immediate release morphine). The route of delivery may be
oral, subcutaneous via a syringe pump or transdermal. Dosages range from MST 10mg
twice a day to very large doses such as MST 1g per day or more.
• Standard post-operative opioid regimes are generally developed for the opioid naïve
patient. Patients on high-dose opioids may have developed a physiological dependence
and, if managed using standard post-operative analgesia regimes, may not receive
adequate analgesia and develop a ‘withdrawal syndrome’. This results in adrenergic
hyperactivity and common symptoms such as fatigue, generalised malaise, abdominal
cramps, perspiration, fever, piloerection, dehydration and restless sleep.
• Patients will require a baseline opioid dosage postoperatively – referred to as the
baseline opioid requirement – calculated using their pre-operative opioid dosage.
This can either be given using the same opioid or using an alternative opioid in an
equi-analgesic dosage. A continuous parenteral infusion may be needed if the patient
is unable to take oral drugs. Provision will need to be made for ‘as required’ dosing for
breakthrough pain. Patient controlled analgesia machines have been successfully used in
opioid dependent patients, with the advantage that dosages and lock-out intervals can
be adjusted according to need.
• In the pre-op and per-operative period, regular opioids (usually oral) may be
discontinued for several hours, which amounts to the opioid “debt”. This should be
replaced with systemic opioids during the operation.
12.3.2 Parenteral opioid delivery
Transdermal drug delivery systems have the disadvantage of being relatively inexible in their dosage
delivery, with clinically relevant dosages still being absorbed for up to 12 hours. One strategy is to
leave the patch in place and to titrate to analgesic eect using immediate release opioids. Similarly, it
may be appropriate to leave implanted analgesic pumps throughout the perioperative period and use
additional short-acting opioids and non-opioids to control breakthrough pain.
12.4 Non-opioid analgesia
Non-opioid analgesic drugs and local anaesthetic procedures will have the eect of reducing opioid requirements
– ‘opioid sparing eect’ (e.g. non steroidal anti-inammatory drugs (NSAIDs), Paracetamol and Clonidine). Local
anaesthetic blocks such as epidurals, brachial plexus block, paravertebral or ilioinguinal blocks will also have an
‘opioid sparing’ eect.

12.5 Eects of surgery
Surgery itself will have a variable eect on opioid requirements and parenteral routes will have to be considered
if the oral route is not available. It is dicult to predict the precise post-operative analgesic requirements because
the eect of surgery may be to increase (if the surgery results in pain due to local tissue trauma) or decrease
opioid requirements. Increases of 20% or more above the baseline opioid requirement have been reported,
depending on the surgical procedure. However, surgery may alleviate pain due to the removal of direct tumour
pressure eects on local structures (e.g. the removal of a retroperitoneal sarcoma tumour pressing on the
lumbosacral plexus). In this group of patients, opioid requirements may reduce but they will still need baseline
opioid administration.
Further reading
James C, Williams JE. How should patients on long-term opioids be managed prior to surgery. British Journal of
Hospital Medicine 2006; 67:500-501.
Lewis NL, Williams JE. Acute pain management in patients receiving opioids for chronic and cancer pain
Continuing Education in Anaesthesia, Critical Care and Pain. 2005;5:127-129.
Mehta V, Langford RM. Acute pain management for opioid dependent patients. Anaesthesia 2006; 61:269-276.
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Chapter 13 Complex problems in cancer pain
Summary
Cancer pain is often very complex, but the most intractable pain is often neuropathic in origin, arising from
tumour invasion of the meninges, spinal cord and dura, nerve roots, plexuses and peripheral nerves. Accurate
diagnosis of the causes of pain is necessary with the use of multimodal therapies. Case studies illustrate some of
these points.
13.1 Introduction
Cancer pain can be complex and dicult to treat. Up to 50% of patients may have pain at diagnosis, and greater
than 75% may experience pain with advanced cancer.
• Pain may occur in more than one site in over half of cases and may have dierent aetiologies. Such
complexity can be challenging and require a truly multidisciplinary approach. As for non-malignant
pain, the management of cancer pain can be challenging for the very young or old, for patients
with medical problems such as heart disease, respiratory disease, renal or liver compromise and
for those with mental health issues. Often these factors may present in combination and generate
demanding clinical problems.
• Certain pain problems related to the nature of the pain or patient factors may make the
conventional WHO ladder approach to pharmacological therapy dicult to utilise and, in some
cases, this approach may not be totally eective. Other pharmacological or more invasive
treatments may be required.
To exemplify these complex issues, we will discuss case studies concerning:
• The problems of breakthrough pain.
• Cancer pain control in patients addicted to opioids.
• The treatment of pain of mucositis.
• Cancer pain in patients with dementia.
• Alternatives to the conventional WHO ladder approach.
• Interventional procedures.
• Ketamine.
13.2 Breakthrough pain
• Breakthrough pain has been referred to as a brief exacerbation of pain on a well-controlled
baseline. The terminology of ‘breakthrough pain’ is undergoing subtle revisions, but is made up of
many dierent types of pain. Breakthrough pain can be of any aetiology. Certain authors feel that
‘breakthrough pain’ does not include exacerbations of pain in the titration phase, nor should an end
of dose exacerbation of pain be called ‘breakthrough’ (William, 2008).
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Breakthrough pain can be divided into
• Spontaneous: no obvious cause.
• Incident pain: clear cause evident.
• Non volitional: pain caused by an involuntary act.
• Volitional: pain caused by a voluntary act.
• Procedural: pain caused by a therapeutic procedure.
As for any cancer pain, treatment relies on detailed assessment and formulation of a multidisciplinary therapy
plan. Rapid acting opioids have been successfully used to treat breakthrough pain, but it remains a dicult
therapeutic problem. Newer preparations of rapid release opioids are being developed.
Case study (breakthrough pain)
A 77-year old man with metastatic cancer of the prostate was admitted to hospital for pain control. He
had been treated for severe back pain and was receiving 30 mg Oxycontin b.d. with 10mg Oxynorm when
required. He had signicant renal impairment (creatinine 340 mol/l) and a history of a previous myocardial
infarction. His main complaint was a signicant worsening of pain on walking, which would keep him in
agony for an hour after walking and meant that he was reluctant to get his usual morning paper. He tried
taking the Oxynorm before going out, which helped with the pain but made him sleepy for the rest of the
morning. He was titrated up with oral transmucosal fentanyl to be used just before walking, and found that
400 μg was sucient to enable him to walk without causing increased drowsiness.

Case study (breakthrough pain)
A 68-year old female with metastatic breast cancer, including bony disease in thoracic and lumbar spine,
was admitted to hospital from home for pain control. Whilst in hospital, she received palliative radiotherapy
and a review of analgesics by the palliative care team. She was taking regular opioids and gabapentin.
Physiotherapy assessment was requested because the patient was keen to return home, but needed
to mobilise short distances indoors. The patient’s pain was well controlled at rest, but she experienced
signicant breakthrough pain (volitional incident pain) whilst transferring out of bed and on mobilising.
Her physiotherapy intervention included:
• TENS machine: the patient was taught where to place pads in the thoracic and lumbar area
and she was advised to use this on the conventional mode. She started treatment 30 minutes
prior to getting out of bed and continued whilst mobilising.
• Relaxation: the patient was taught simple diaphragmatic breathing exercises to help her
prepare for mobilising.
• Mobility work: timed with the use of the Fentanyl lozenge and mobility with a Zimmer frame
to assist weight-bearing. Pacing techniques were used to gradually increase the distances
covered.
• Using the above techniques ensured that the patient was able to get out of bed
independently and mobilise short distances (<10metres) using her walking aid.
13.3 Pain in opioid addiction and substance misuse
• In the UK, the prevalence of drug misuse is around 9 per 1,000 of the population aged 15-64 years,
and around 3 per 1,000 injected drugs in the case of most opioids. Opioid abuse and dependence
are associated with a wide range of problems, including overdose, HIV infection, Hepatitis B or C,
thrombosis, anaemia, poor nutrition, dental disease, infections and abscesses, criminal behaviour,
relationship breakdown, unemployment, imprisonment, social exclusion and prostitution.
13.3.1 Pain from cancer in people who are addicted to opioids may be under-treated for
the following reasons:
• Lack of understanding of opioid addiction and methadone maintenance.
• Lack of training on prescribing analgesia in this group of patients.
• Attitude of healthcare professionals about illicit drug users; fear of diversion.
• Failure to recognise the potential for tolerance to other opioids in Methadone-
maintained patients.
• Acute pain may be under-treated leading to misunderstandings, patient anxiety,
depression, dissatisfaction and complaints.
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13.3.2 Principles of giving analgesia in opioid-addicted patients:
• Prevent withdrawal symptoms/complications.
• Assess opioid load (in an intravenous (i.v.) drug user this is dicult; withdrawal symptoms
can be prevented using low doses of opioids).
• Diagnose the cause of the pain: nociceptive, inammatory, neuropathic, visceral, mixed.
• Use balanced analgesia wherever possible: NSAIDs, paracetamol, local anaesthetics,
tricyclic antidepressants, anticonvulsants.
• Use oral/ transdermal/ subcutaneous routes, rather than intravenous ones. Consider
epidural or intrathecal drug delivery systems, remembering the infection risk.
• Use long-acting opioids and minimise analgesia for breakthrough, as this may be
rapidly escalated. Set a limit and review frequently. Use tablets (Sevredol, Oxynorm) for
breakthrough pain, not Oramorph.
• Make a “contract” with the patient before starting therapy, explaining the limitations
and setting a clearly dened upper limit of opioids before the next review. Write clear
instructions for the whole team.
• Use a sole prescriber (usually GP). Prescriptions may have to be issued daily, every 2 -3
days or weekly.
• Use psychological therapies and treat anxiety and depression.
13.3.3 Maintenance Therapy
Methadone substitution is the primary maintenance treatment in the UK, usually 60-120 mg daily.
There may be tolerance to other opioids, and a rapid escalation of doses can be dangerous, especially
when combined with alcohol or other sedative drugs.
Naltrexone (opioid antagonist) is used in detoxication programmes to help maintain abstinence. It
is long acting (>48hrs) and will lead to opioid resistance and then opioid sensitivity when it has been
eliminated systemically.
Buprenorphine (partial agonist) is also used to prevent withdrawal symptoms in opioid dependent
patients. Its action on the µ receptors reduces the eects of any additional opioids. Average
maintenance doses range between 12 and 24 mg daily. Patients with severe cancer pain may have to
be changed from buprenorphine to methadone.

Case Study (opioid addiction)
A man of 52 years was admitted to a hospice from prison. He had been an i.v. drug user and had hepatitis
B and C and carcinoma of the lung. He was complaining of severe upper chest pain and neuropathic pain
radiating down the right arm. There were no focal neurological abnormalities. He had had radiotherapy
and chemotherapy. No further treatment of his cancer was planned. He was due to return home after
this admission for symptom control. He denied taking drugs while in prison, and was not on methadone,
but morphine sulfate slow release (MST) 300mg b.d. and Oramorph, which had escalated from 200mg to
600mg daily over a 48-hour period. Despite this, the pain had not been relieved.
Adjunct therapy: gabapentin 600mg tds, amitriptyline 50mg, diazepam 10mg tds.
An agreement was made that oramorph was ineective for his pain and would be stopped completely.
MST was halved to 150 mg b.d. and methadone 10 mg b.d. started. Over two weeks, his MST was reduced
gradually and stopped and methadone increased to 60mg b.d.
His pain was controlled and he left the hospice with only paracetamol for breakthrough pain and strict
instructions not to increase methadone without medical advice.
(NB. Alcohol should not be used while switching to methadone from other opioids because cases of
sudden death have been reported.)
13.4 Mucositis
Mucositis is the painful inammation and ulceration of the mucousmembranes, which usually occurs in the
mouth but can aect other areas of the mucosa in the gastro-intestinal tract (Trotti, 2003; Clarkson, 2007). It
can be caused by radiation therapy or chemotherapy and is very common after radiotherapy for cancer of the
head and neck and after certain types of chemotherapy, such as 5-uorouracil. High-dose chemotherapy and
hematopoietic stem cell transplantation have an especially high incidence of oral mucositis (Sonis, 2004; Clarkson,
2007).
• Non-pharmacological treatment strategies include meticulous oral hygiene, gel-based barrier
protection, the reduction of known painful precipitants (e.g. alcohol), local anaesthetic mouth
washes and other oral lubricants. Opioids provide the mainstay of pharmacological treatment,
but newer anti-inammatory therapies are being developed. However, severe oral mucositis often
causes diculties in swallowing, precluding the use of oral medication.
Case study (mucositis)
A 36-year old man with acute lymphocytic leukaemia developed grade 3 mucositis (unable to eat solids)
7 days after an autologous stem cell transplantation. Although he had little pain most of the time, severe
pain prevented him eating, and drinking was very uncomfortable. He had been put on regular four-hourly
Oromorph, which helped with the pain, but he was reluctant to take it because this hurt so much and
he was unhappy at being drowsy. Barrier gel helped slightly, but he was still unable to tolerate much oral
intake. A morphine patient controlled analgesic (PCA) device was used with a 2 mg bolus, 5 min lockout
time, without a background infusion. By using the PCA, he managed to accept a soft diet and experience
very little drowsiness. He continued the PCA for 5 days until the mucositis was healing.
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13.5 Pain in Dementia suerers
Adults with dementia will probably express their pain in ways that are quite dierent from their cognitively intact
counterparts, which can result in inadequate pain assessment and consequently poor pain management.
The processing of sensory-discriminative aspects of pain in the brain are thought to occur in the lateral pain
system, whereas motivational-aective aspects are processed by the medial system. The recognition of these
two systems is important when dealing with patients with dementia. Pain thresholds (which are the sensory-
discriminative aspects) do not dier between patients with Alzheimer’s disease and those older adults without
dementia, although pain tolerance (motivational-aective aspect) does. Older adults with Alzheimer’s disease
perceive the presence of pain, but the intensity and aective aspects are dierent to those experienced by their
cognitively intact counterparts. This might explain the atypical behavioural responses observed in this group.
Observation of the behaviour for pain assessment in patients who do not have the ability to communicate
their pain can be helpful, but typical pain behaviours may be absent or dicult to interpret. The involvement of
healthcare professionals, informal care providers and the family in the identication of pain is essential.
The American Geriatric Society (2002) lists 6 categories of pain behaviours and indicators for older people with
dementia:
• Facial expressions.
• Verbalisations and vocalisations.
• Body movements.
• Changes in interpersonal interactions.
• Changes in activity patterns or routines.
• Mental status changes.
A number of behavioural pain assessment tools exist for detecting the presence of pain in patients with dementia.
Care providers are advised to select a tool that is appropriate to the patient and that can be used for initial and
ongoing assessments. However, the assessment of behavioural pain indicators should consider only one strategy
to identify pain in patients with dementia, and should be used in conjunction with other pain assessment
strategies and the evaluation of pain relieving interventions.

Case study (dementia)
A 63-year old woman with disseminated breast carcinoma and a previous history of Alzheimer’s disease
was admitted after becoming unwell at home. She had previously been on 20 mg Zomorph (sustained
release morphine) twice a day for pain associated with lumbar spinal metastasis. Severe constipation and
a urinary tract infection were diagnosed and after two days of treatment, her family said that she was
returning back to normal. Opioids were switched to 10 mg Oxycontin (sustained release oxycodone) twice
a day. However, on the 3rd day she became withdrawn rst towards sta and then towards her family, and
became reluctant to get out of bed, often shouting out when this was attempted. She refused any type
of examination. After careful assessment, it was recognised that she was in pain and she agreed to take
10mg Oxynorm (immediate release oxycodone) liquid. Half an hour later, she started interacting with her
family and sta. She then allowed examination and tenderness was elicited in her right groin. A pelvic X-ray
revealed a pathological fracture of her right pubic ramus.
13.6 Use of interventional techniques
• Invasive techniques provide analgesic possibilities when conventional treatments fail. This might
be because of the unacceptable side-eects of opioids, or if the pain is less opioid sensitive. Spinal
and epidural infusions can be highly eective in relieving refractory severe pain, albeit requiring
anaesthetic input and specialist equipment.
• Nerve blocks add to the treatment options available for pain that is challenging to manage,
although achieving long-term benets can be problematic. Nerve ablation provides a method of
sustained relief, but increases the risk of side-eects. Direct tumour ablation or cement xation of
metastatic bony disease is being used more frequently for bone pain, with good results (Gangi,
1994, 2003).
• Interventional techniques are by denition more invasive, often requiring nursing and medical
input, and are associated with potential side-eects and problems. However, the possibility of
analgesia often outweighs the risks in patients with uncontrolled pain. Although the evidence base
for many of these interventions is limited and some is extrapolated from other studies of cancer
pains or nonmalignant pain, interventional techniques are used extensively, safely and eectively
(see chapter 8). They form an integral part of the multidisciplinary approach to cancer bone pain
management, and their early consideration may often be warranted.
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Case study (interventional management)
A 57-year old man with a history of metastatic colonic carcinoma was admitted to an acute hospital with
a pathological fractured neck of femur. His pain was dicult to control with opioids and NSAIDs, especially
the pain on movement. The acute pain team inserted an epidural catheter. Unfortunately the block was
unilateral, blocking the uninjured side and decreasing mobility without any meaningful analgesia for the
fractured limb. The fracture was considered inoperable and the patient was transferred to a specialist
cancer hospital for consideration of further treatment. Analgesia continued to be problematic. High doses
of morphine managed to reduce rest pain, but were associated with increased somnolence and continuing
constipation. The patient was unwilling to have another epidural catheter due to a fear of a repeated
unilateral block. After discussion, the patient was oered a lumbar plexus catheter, which was inserted
easily when the patient was awake using only local anaesthetic. A bupivacaine (0.1%) and fentanyl (2mcg/
ml) infusion at 10ml/hr into the lumbar plexus achieved good pain relief at rest and on movement. The
increased analgesia on movement and the retained motor strength on the uninjured side allowed the
patient to mobilise.
13.7 Atypical pharmacological treatments: ketamine
• The N-methyl-D-aspartate (NMDA) receptor has been implicated in mechanisms of neuropathic
and inammatory chronic pain. It is one of the key components of central sensitisation that
contributes to increased pain and abnormal pain perception. It is also thought to be involved in
many cancer pains. When the conventional WHO ladder approach fails, NMDA receptor antagonists
could provide a novel and powerful site of analgesia.
• There is evidence for the ecacy of NMDA receptor antagonists in many chronic pains (including
cancer pain), yet the situation is not so clear from a clinical perspective. There are few NMDA
receptor antagonists available. Dextromethorphan has been used for acute pain. Methadone also
has some NMDA antagonist activity and may help in some cases of opioid refractory pain. However,
ketamine is the most used NMD receptor antagonist for cancer pain.
• Ketamine is an anaesthetic, but in smaller doses appears to have analgesic properties. There are
many case reports and case series demonstrating signicant ecacy in refractory cancer pain,
either alone or concomitantly with opioids. However, there is little higher quality evidence (such as
RCTs) at present. The lack of data is reected in the variability of suggested protocols in both dose
and route of administration. Side-eects are potentially problematic, including tachycardia and
cognitive disturbances such as hallucinations. Nevertheless, ketamine may provide some empirical
benet in refractory cancer pain.

Case study (ketamine)
A 41-year old man with recent diagnosis of myeloma was undergoing investigation prior to chemotherapy.
He was noted to have a creatinine of 250 mmol/l. While an in-patient, he experienced sudden extreme
and severe pain in the centre of his centre chest after minimal trauma. An X-ray conrmed a fracture of his
sternum. Parenteral (i.v.) opioids were only partially eective and were associated with dizziness, sickness
and sleepiness. NSAIDs were not considered in view of his renal impairment. Use of i.v. ketamine bolus (0.15
mg/kg) followed by a continuous infusion (1mg/kg/hr) rapidly brought the pain under control to allow an
MRI scan. After 36 hours of infusion, he was assessed for and received a thoracic epidural. The ketamine was
stopped and 0.15 % bupivacaine with 4 mcg/ml fentanyl was infused at 10 ml/hr to give good analgesia.
The epidural remained in situ for 5 weeks until sternum was healing well, although a persistent pyrexia
and subsequent MRI scan showed the complication of an epidural abscess. This resolved on conservative
management.
Case study (ketamine)
A 37-year old woman with previous cancer of cervix and a recurrence three years ago (treated with
chemotherapy and radiotherapy) was admitted for the relief of severe back pain. This had made her
unable to get out of bed. She also had a previous history of degenerative back disease and long-term
steroids. She had been given 20 mg 4 hourly of Oromorph by her GP, which made her sick. Investigation
diagnosed vertebral collapse of her 4th lumbar vertebra. Pain was controlled with i.v. ketamine in the
acute phase. Subsequently, she had a tunnelled intrathecal catheter inserted with an implanted pump that
infused intrathecal diamorphine. She was pain free and managed to mobilise well. She was referred for
vertebroplasty and in the interim managed to go home with the pump in situ.
13.8 Pain in children and adolescents with cancer
Pain in children and adolescents with cancer is a signicant, debilitating, acute and chronic symptom during or
after treatment that aects the quality of life of young patients and their families. In recent years, advances in pain
management have been made; however, pain remains often under-treated and there is a need for improvement.
The principles of pain management and palliative care in adult practice are relevant to paediatrics; nevertheless,
the adult model cannot be applied directly to children for the following reasons (McCulloch, 2008):
(a) The types of malignancy and disease trajectory in children are dierent from those in adults;
(b) Special considerations are required when selecting analgesics, doses and modalities during childhood. Factors
that inuence prescribing are quite distinctive from adults and include metabolism, renal clearance, changing size
and surface area and the ability to manage medication, among others;
(c) A child’s family and social context is dierent to that of an adult: relationships with parents and siblings, school
and friends and the extended family network are of paramount importance when treating young patients;
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(d) A child’s developmental stage and continuous psychological, spiritual and cognitive development need to be
taken into account when treating their pain (e.g. a child’s conceptualization of what causes and eases pain, their
understanding of time and their ability to implement behavioural and cognitive strategies for coping with pain);
(e) The legal and moral positions regarding the decision-making ability of both those with parental responsibility
and the child/ young person themselves is very dierent to those of an adult.
Eective pain management in children and young people with cancer requires that paediatric healthcare
providers take into account the multitude of physiological and psychological changes that occur from infancy
through adolescence, including changes in relationships with parents (Wolfe, 2000). The multidisciplinary
approach to providing pain management for children and adolescents includes integrating pharmacological and
psychosocial care in the context of each patient’s physical, cognitive, emotional and spiritual level of development
(Liossi, 2002).
Every child/ young person with pain management and palliative care needs should have access to universal
paediatric services, core palliative care services (hospice, community palliative care nurses) and specialist palliative
care support when required (Department of Health, 2005).

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2008:44(8);1139-45.
Sonis ST. The pathobiology of mucositis. Nature reviews Cancer 2004;4(4):277-84.
Trotti A, Bellm LA, Epstein JB, Frame D, Fuchs HJ, Gwede CK, Komaro E, Nalysnyk L, Zilberberg MD. Mucositis
incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or
without chemotherapy: a systematic literature review. Radiotherapy and Oncology 2003;66:253–262.
William L, Macleod, R. Management of breakthrough pain in cancer patients. Drugs 2008;68 (7):913-924
Wolfe J, Grier HE, Klar N, Levin SB, Ellenbogen JM, Salem-Schatz S, Emanuel EJ, Weeks JC. Symptoms and suering
at the end of life in children with cancer. New England Journal of Medicine 2000;342(5):326-33.
Further reading
Bell R, Eccleston C, Kalso E. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Systematic
Review 2003. 1:CD003351.
Davies A. Cancer related breakthrough pain. Oxford Pain Library, OUP. Farquhar-Smith WP (2008). Anaesthetic/
interventional techniques. In: Cancer related bone pain, ed. Davies A, Oxford Pain Library, OUP.
Herr K, Bjoro K, Decker S. Tools for assessment of pain in nonverbal older adults with dementia: a state of the
science review. Journal of Pain & Symptom Management 2006;31(2):170-92.
Kirsh KL, Passik SD. Palliative care of the terminally ill drug addict. Palliative Care 2006;24(4):425-31.
Murphy BA. Clinical and economic consequences of mucositis induced by chemotherapy and/or radiation
therapy; Suppliment 2007;4:13-21.
Okon, T. Ketamine: an introduction for the pain and palliative medicine physician. Pain Physician 2007;10:493-500
Scherder E, Oosterman J, Swaab D, Herr K, Ooms M, Ribbe M, Sergeant J, Pickering G, Benedetti F. Recent
developments in pain in dementia. British Medical Journal 2005;330;(7489):461-464.
Worthington HV, Clarkson JE, Eden OB. Interventions for preventing oral mucositis for patients with cancer
receiving treatment 2007;17;(4):CD000978.
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Chapter 14 Cancer pain: recommendations for service design
and training
Summary
The management of cancer pain can and should be improved by better collaboration between the disciplines
of oncology, pain medicine and palliative medicine. This must start in the training programmes of doctors, but
also in established teams in terms of funding and time for joint working, and in the education of all healthcare
professionals involved in the treatment of cancer pain.
14.1 Surveys of working with Pain Management and Palliative Care
• Despite the recognised need for improved pain management in palliative care, there is currently
inconsistent partnership between the specialities of pain medicine and palliative medicine.
• A national survey of pain management services in palliative care was conducted in 2002 by
Linklater, who sent a postal questionnaire to all consultant members of the Association for Palliative
Medicine, asking whether they had contact with a pain management specialist. Most respondents
had access to “as-required” anaesthetic pain consultations, with 72% feeling that the frequency
of consultation was adequate, but 20% desiring more frequent input. 15% had access to regular
weekly sessions; trainee anaesthetists featured in only 7% of sessions. Half the respondents used
pain management advice less than four times a year. All respondents felt that the anaesthetist’s
input involved advice on performing practical procedures, but only 25% felt that a joint
consultation about analgesic therapy would be useful. The authors advocated the establishment
of a regular weekly session with a pain specialist, and their experience showed that this rapidly
increased the number of referrals to 11% of in-patients, with procedures performed on 8% and
advice given on 3% of cases.
• A survey of anaesthetists in UK clinics was conducted in 2007 by Kay using a postal questionnaire
and they found that referrals rates from palliative medicine to pain clinics were low; only 31% of
respondents received more than 12 referrals per year. Only 25% of anaesthetists’ job plans had time
allocated for palliative medicine referrals, and joint consultations were rare.
• A 2007 survey of hospices and palliative care units in England (Petrovic, personal correspondence)
has shown that, while 92% of palliative care units have access to specialist pain management
advice, only 16% have regular sessions; the situation has not changed over the past 5 years, despite
the increasing complexity of illness. Only 41% of pain services provided a comprehensive range of
pain treatments, including non-invasive therapies such as TENS and minimally invasive therapies
such as acupuncture and trigger point injections, and in about 50% of palliative care units, neuraxial
infusions are not available. There are distinct barriers to sending patients home with invasive
therapies related to multiple factors, but particularly to a lack of training and the experience of the
home care team and drug supply issues.
14.2 Barriers to links between specialist pain management and palliative medicine
These can be summarised as follows:
• Short survival of patients following referral to palliative care services.
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• Funding of the service.
• Time on the part of the pain specialist for proper assessment and discussion.
• Facilities for performing interventions may not be easily accessible.
• Complexity/lack of real understanding.
• Sta training in the management of pumps and catheters.
• Pharmacy issues; procurement of solutions/ availability of preservative free opioids/ lack of sterile
facilities for making up infusions.
• Cost of implanted devices.
• Who is going to manage neuraxial infusions at home?
• Lack of availability of pain specialists out of hours.
• The palliative care doctor may be unaware of potential benets/ unsure how to access expertise.
• The pain doctor may not be adequately trained in the management of cancer pain/ selection of an
appropriate technique.
There are examples in the literature of improved treatment outcomes from a multidisciplinary cancer pain
clinic. A Danish study in 1991 showed an improvement in pain scores in over 50% of patients using medical
pain treatment supplemented by analgesic tailoring, epidural opioid therapy, non-neurolytic blockades and
combinations of these (Banning, 1991).
14.3 What can specialist pain management oer in palliative care?
• Assessment of complex cases.
• Detailed knowledge of the neurophysiology of pain.
• Specialist knowledge of treating dierent types of pain (e.g. neuropathic pain, complex regional
pain syndrome).
• Interventional techniques.
• TENS, acupuncture.
• Psychological aspects of pain management.
• Provision of sedation.
• Management of non malignant pain.
• Recognition and advice about dependency and addiction.
• Withdrawal from opioids.

14.4 What can palliative medicine oer to specialist pain management?
• Detailed knowledge of using opioids.
• Management of opioid toxicity.
• Understanding of cancer pain and all cancer treatments.
• Excellent communication skills.
• Team working.
• Family therapy.
• Holistic medicine.
• Home care.
• End of life care.
14.5 Improving collaboration
Palliative medicine has been a recognised speciality since 1987, when speciality training programmes were
established by the Royal College of Physicians. Funding of the speciality was further enhanced as a result of the
Calman-Hine report in 1995, when palliative care was integrated with cancer services. Pain medicine is not yet a
recognised speciality, although a Faculty of Pain Medicine of the Royal College of Anaesthetists was established
in April 2007 to set and uphold standards in the training of doctors practising pain medicine in the future. Cancer
pain management will be an essential part of this training. Interventional pain control is also a vital part of the
training of palliative medicine doctors, thus providing hope for enhanced collaboration in the future. The training
requirements detailed in 14.6 will enhance the knowledge of doctors in the future about pain management and
palliative care. It is hoped that similar provision will be made in the training programme of medical oncologists.
It is important that nurses, physiotherapists, pharmacists and other healthcare professionals will also introduce the
principles of multimodal pain management into their curricula.
14.5.1 Other ways in which collaboration can be improved
• Regular funded sessions for the pain specialist to work in palliative care, whether in
hospital, the community or a hospice.
• Regular discussion about individual cases.
• Timetabled attendance of all types of healthcare professionals on joint ward rounds and
at multidisciplinary meetings.
• Joint educational seminars, local and national.
• Joint national and international meetings (e.g. British Pain Society Annual Scientic
Meeting, World Congress on Pain).
• Joint research projects and publications.
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• Provision for out-of-hours management of neuraxial infusions should be decided by local
protocols and agreement.
There is no doubt that the management of cancer pain could and should be improved by the breaking
down of professional barriers between disciplines, not only of doctors, but also of nurses and other
professional bodies. The hospice movement in the UK can lead to professional isolation, so more
eort needs to be made to establish coherent, funded, collaborative pain services. The training of pain
doctors must include a signicant time devoted to the management of cancer pain.
14.6 Education and training
The Specialist Advisory Committee for Palliative Medicine at the Royal College of Physicians is responsible for the
curriculum for trainees in palliative medicine and includes such topics as physiology, the management of chronic
pain, nerve blocks, the management of spinal catheters, opioid dependency and the psychology of pain.
The Faculty of Pain Medicine of the Royal College of Anaesthetists was established in April 2007 to set and uphold
standards in the training of doctors practising pain medicine. The curriculum for advanced pain trainees is not yet
nalised, but there is a clear intention to improve training in the management of cancer pain and trainees must
acquire experience of interventional techniques and know when to apply them.
There are MSc courses available in pain management and palliative care. A joint course on interventional pain
control in cancer pain management is held annually between King’s College Hospital and St Christopher’s
Hospice.
National scientic meetings are held by the British Pain Society (www.britishpainsociety.org) and the Association
for Palliative Medicine (www.palliative-medicine.org), and international meetings are held by the International
Association for the Study of Pain (www.iasp-pain.org) and the European Association for Palliative Care
(www.eapcnet.org).
14.7 Research agenda
There is a need for further study in the following areas:
• Better understanding of the basic mechanisms of cancer pain (visceral, neuropathic and bone pain).
• Researching ways of implementing existing knowledge into routine practice (e.g. pain assessment,
feeding assessment data to clinicians, the use of prescribing protocols).
• Review and standardise the methodology for evaluating non-pharmacological interventions in
cancer pain.
• Understanding mechanisms through which patient based education on cancer pain and analgesia
works (e.g. does it improve medication adherence, reduce anxiety by allying fears, increase coping,
etc.?).
• Clinical trials of add-on therapies (e.g. are combination opioids better than mono-opioid therapy?).
• Building capacity to undertake clinical studies in cancer pain management (e.g. investing in
academic departments to support pain management and palliative medicine, identifying CLRNs
and cancer research networks that can undertake these trials, increase opportunity for PhD studies
in cancer pain management).

References
A Report by the Expert Advisory Group on Cancer to the Chief Medical Ocers of England and Wales. A Policy
Framework for Commissioning Cancer Services (The Calman-Hine Report). London: Department of Health, 1995.
Banning A, Sjøgren P, Henriksen H. Treatment outcome in a multidisciplinary cancer pain clinic. Pain 1991;47:129-
134.
Kay S, Husbands E, Antrobus JH, Munday D. Provision for advanced pain management techniques in adult
palliative care: a national survey of anaesthetic pain specialists. Palliative Medicine 2007;21:279-284.
Linklater GT, Leng MEF, Tiernan EJ, Lee MA, Chambers WA. Pain management services in palliative care: a national
survey. Pain Reviews 2002;9:135-140.
Petrovic Z, Hester JB. A national survey of pain management services in palliative care 2007 (personal
correspondence).
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Membership of group and expert contributors
Chair and Editor
Jon Raphael
Professor of Pain Medicine and member of the British Pain Society
Members of the group
Sam H Ahmedzai
Professor of Palliative Medicine and the Association of Palliative Medicine
Janette Barrie
Nurse Consultant
Michael Bennett
Professor of Palliative Medicine
Marie Fallon
Professor of Palliative Medicine
Paul Farqhuar-Smith
Consultant in Pain Medicine, Anaesthesia and Intensive Care and member of the British Pain Society
Rebecca Haines
Consultant Psychologist
Joan Hester
Consultant in Pain Medicine and member of the British Pain Society
Martin Johnson
General Practitioner and member of the Royal College of General Practitioners
Karen Robb
Consultant Physiotherapist
Catherine Urch
Consultant in Palliative Medicine
Heather Wallace
Patient representative
John Williams
Consultant in Pain Medicine and Anaesthesia and member of the British Pain Society
The group gratefully acknowledges contribution from
Arun Bhaskar
Consultant in Pain Medicine

Sam Chong
Consultant Neurologist
James de Courcey
Consultant in Pain Medicine and Anaesthesia
Rui Duarte
Research Psychologist
Charlie Ewer-Smith
Occupational Therapist
Peter Hoskin
Professor of Clinical Oncology
Christina Liossi
Senior Lecturer in Health Psychology
Renee McCulloch
Consultant in Paediatric Palliative Medicine
Max H Pittler
Senior Research Fellow, Complementary Medicine
Dilini Rajapakse
Consultant in Paediatric Palliative Medicine
Brian Simpson
Consultant Neurosurgeon
Elizabeth Sparkes
Lecturer in Psychology
Barbara Wider
Research Fellow, Complementary Medicine
Ann Young
Consultant in Pain Medicine and Anaesthesia
Competing interests
Members of the group have registered all competing interests as follows:
Professor Sam H Ahmedzai has received unrestricted research or educational grants and honoraria for lectures
and consultancies from the following companies who have an interest in cancer pain management: Cephalon,
Grunenthal, Janssen-Cilag, Mindipharma, Napp, Pzer, Prostrakan.
Professor Michael Bennett has received unrestricted research funds and honoraria from various companies
including NAPP, Pzer and Cephalon.
Dr Paul Farquhar-Smith has been involved in NAPP sponsored discussions.
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2
e authors gratefully acknowledge the assistance of Yves Lebrec (publication)

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