Figure 2 - uploaded by Robert Martin Bennett
Content may be subject to copyright.
Radiograph of a hand in moderately advanced acromegaly showing a mixture of joint space enlargement and degenerative changes.
Source publication
Growth hormone is essential for normal linear growth and the attainment of an adult mature height. It also plays an important role in cartilage growth and the attainment of normal bone mass. There is only one rheumatic disorder, namely acromegaly, in which abnormalities of growth hormone production play a major etiologic role. However, there is inc...
Context in source publication
Context 1
... diagnosis of acromegaly is based on the typical clinical features in conjunction with a consistently elevated IGF-1 level [15•] (Fig. 2). The levels of GH itself are also elevated, but this is a less reliable screening test as the measurement of GH is subject to more variation because of pulsatile secretion. It is important to remember that IGF-1 levels vary significantly with age, with the highest levels being seen in early puberty. Thus, an IGF-1 level that would be normal in puberty could be indicative of a GH secreting pituitary adenoma in a ...
Similar publications
Joint hypermobility syndrome (JHS) is common in patients presenting to rheumatologists and can cause a range of symptoms leading to physical and psychological distress. Chronic musculoskeletal pain in patients with JHS often responds poorly to analgesics, and a pain management approach may be helpful. Since patients with JHS often have beliefs and...
India is home to the world's second largest population. Rheumatology is an emerging specialty in India. We reviewed organization, epidemiology and training facilities for Rheumatology in India. Also, we also looked at publications in the field of rheumatology from India from over the past six years using Scopus and Medline databases. Despite rheuma...
Citations
... Coincide with this study; treatment with 2 mg/kg HGH stimulates the cartilage growth and higher cartilage thickness in rabbits [6]. In addition, GH defeats inflammatory pain through the role of IGF-1 by overcoming the inflammation and prostaglandin which have a role as the pain mediator [1,3]. In other studies, the healing of the cartilage was generated after the intra articular injection of GH [9,16,8]. ...
Recombinant human growth hormone (rHGH) which plays an important role for remodeling of bone has an effect on cartilage differentiation and regeneration, as well. Herein, we reviewed human growth hormone and its roles on cartilage. We discussed different roles on growth, regeneration, inflammation, cell maturation, and mitotic activity. These findings provide proof of principle that therapeutics based on rHGH can improve treatment for numerous disorders.
... Ghrelin, the endogenous ligand for the GH secretagogue receptor, has been reported to have antinociceptive effects. Disturbance of the GH/IGF-1/ghrenlin paracrine axis has been linked to painful conditions such as fibromyalgia and inflammatory and rheumatic diseases [3][4][5][6][7][8]. Treatment with GH for fibromyalgia and chronic lower V C 2019 American Academy of Pain Medicine. ...
... GH/IGF-1 axis abnormalities have been associated with several rheumatic diseases [4]. A review of the literature suggested that serum GH levels are elevated in patients with osteoarthritis (OA), rheumatoid arthritis (RA), and diffuse idiopathic skeletal hyperostosis but not in patients with gout, pseudogout, or systemic lupus erythematosus [8]. ...
Objective:
Growth hormone (GH) and GH-related signaling molecules play an important role in nociception and development of chronic pain. This review aims to examine the potential molecular mechanisms through which GH-related signaling modulates sensory hypersensitivity in rodents, the clinical pharmacology of GH, and the clinical evidence of GH treatment for several common pain syndromes.
Methods:
A search was conducted using the PUBMED/MEDLINE database, Scopus, and the Cochrane library for all reports published in English on GH in pain management from inception through May 2018. A critical review was performed on the mechanisms of GH-related signaling and the pharmacology of GH. The levels of clinical evidence and implications for recommendations of all of the included studies were graded.
Results:
The search yielded 379 articles, of which 201 articles were deemed irrelevant by reading the titles. There were 53 reports deemed relevant after reading abstracts. All of these 53 articles were retrieved for the analysis and discussion.
Conclusions:
Dysfunction of the GH/insulin-like growth factor 1 (IGF-1)/ghrelin axis was linked to hyperalgesia and several common clinical pain syndromes. Low levels of GH and IGF-1 were linked to pain hypersensitivity, whereas ghrelin appeared to provide analgesic effects. Pretreatment of GH reversed mechanical and thermal hypersensitivity in an animal model of inflammatory pain. Clinical trials support GH treatment in a subgroup of patients with fibromyalgia syndrome (level of evidence: 1B+) or chronic lower back pain syndrome (level of evidence: 2C+).
... Injection of GH as a single agent does not have mechanical ef fect or local antiinflammatory effect at the joint 8,16) . The effect of GH in overcoming inflammatory pain is through the indirect role of cortisol and IGF1 which suppress the inflammatory process and prostaglandin that act as the pain mediator 14,17) . The assessment of pain scale in this study was highly dependent on the observer. ...
Purpose:
Up to now, there is no feasible solution for stopping or reversing the degenerative process of osteoarthritis (OA). Our study evaluated the effect of intra-articular injection of growth hormone (GH) in OA-induced rabbit knees compared to hyaluronic acid (HA) and placebo.
Materials and methods:
A total of 21 male, skeletally mature, New Zealand rabbits received an intra-articular type II collagenase injection for OA induction. Two weeks later, the rabbits were randomized into three groups based on the weekly intra-articular injection to be received: GH, HA, and saline. Injections were done for three consecutive weeks. Evaluation was done at 8 weeks after treatment, clinically using the lameness period, macroscopically using the Yoshimi score and microscopically using the Mankin score.
Results:
The shortest period of lameness was found in the GH group (15.9±2.12 days), compared to the HA group (19.4±1.72 days) and placebo group (25.0±2.94 days). There was a statistically significant difference in macroscopic scoring between groups (p=0.001) in favor of the GH group. There was also significant difference in the microscopic score between groups (p=0.001) also in favor of the GH group.
Conclusions:
Intra-articular injection of GH showed better clinical, macroscopic and microscopic results as compared to HA and placebo.
... Both growth and post-injury tissue repair are influenced by the GH signaling cascade (Lanning and Carter-Su, 2007;Rosenfeld and Hwa, 2009). In addition, there have been a few recent reports that patients with growth hormone deficiency (GHD) often have a resting pain in their limbs (Cimaz et al., 2001;Bennett, 2004). ...
... Reports show that GHD can be associated with pain (Bennett, 2004;Cuatrecasas et al., 2010;Cimaz et al., 2001). We found that developing GHRHr −/− mice display mechanical and heat hypersensitivity in an age-related fashion ( Fig. 1-3). ...
... Male GHRHr−/ − did eventually display mechanical hypersensitivity by P14. Although to our knowledge, no sex specific effects of GHD are well-documented regarding pain, reports do indicate that GH may be a strong modulator of sensory function during early stages of life (Liu et al., 2017;Bennett 2004;Cimaz et al. 2001;Devesa et al., 2017). Results of our current report support this notion as by P21, GHRHr−/− mice did not display any evoked hypersensitivity like P7 and P14 animals (Figs. ...
Injury during early postnatal life causes acute alterations in afferent function and DRG gene expression, which in addition to producing short-term sensitivity has the potential to influence nociceptive responses in adulthood. We recently discovered that growth hormone (GH) is a key regulator of afferent sensitization and pain-related behaviors during developmental inflammation of the skin. Peripheral injury caused a significant reduction in cutaneous GH levels, which corresponded with the observed hypersensitivity. However, it has yet to be determined whether GH deficiency (GHD) is sufficient to drive peripheral sensitization in uninjured animals. Here, we found that systemic GHD, induced by knockout of the GH release hormone receptor (GHRHr), was able to induce behavioral and afferent hypersensitivity to peripheral stimuli specifically during early developmental stages. GHD also produced an upregulation of many receptors and channels linked to nociceptive processing in the DRGs at these early postnatal ages (P7 and P14). Surprisingly, P21 GHRHr knockouts also displayed significant alterations in DRG gene expression even though behavioral and afferent hypersensitivity resolved. These data support previous findings that GH is a key modulator of neonatal hypersensitivity. Results may provide insight into whether GH treatment may be a therapeutic strategy for pediatric pain.
... It was shown that prolonged systemically applied GH therapy improves overall symptomatology, including the number of tender points in fibromyalgia patients (Bennett et al., 1998). It was also suggested that bone and muscle deficiencies may result in resting pain through GH deficiency (Bennett, 2004). Overall, a majority of clinical studies indicate that GH increase directly leads to severe pain, while few reports imply that GH shortage resulted in abnormalities indirectly affecting resting pain. ...
Clinical and basic research on regulation of pituitary hormones, extra-pituitary release of these hormones, distribution of their receptors and cell signaling pathways recruited upon receptor binding suggests that pituitary hormones can regulate mechanisms of nociceptive transmission in multiple orofacial pain conditions. Moreover, many pituitary hormones either regulate glands that produce gonadal hormones (GnH) or are regulated by GnH. This implies that pituitary hormones may be involved in sex-dependent mechanisms of orofacial pain and could help explain why certain orofacial pain conditions are more prevalent in women than men. Overall, regulation of nociception by pituitary hormones is a relatively new and emerging area of pain research. The aims of this review article are to: (1) present an overview of clinical conditions leading to orofacial pain that are associated with alterations of serum pituitary hormone levels; (2) discuss proposed mechanisms of how pituitary hormones could regulate nociceptive transmission; and (3) outline how pituitary hormones could regulate nociception in a sex-specific fashion. Pituitary hormones are routinely used for hormonal replacement therapy, while both receptor antagonists and agonists are used to manage certain pathological conditions related to hormonal imbalance. Administration of these hormones may also have a place in the treatment of pain, including orofacial pain. Hence, understanding the involvement of pituitary hormones in orofacial pain, especially sex-dependent aspects of such pain, is essential to both optimize current therapies as well as provide novel and sex-specific pharmacology for a diversity of associated conditions.
... Most of these actions are stimulated by insulin-like growth factor-1 (IGF-1) rather than GH itself. GH also promotes the secretion of IGF-1 from the liver by binding to the specific receptor [8]. IGFs are bound to circulating binding proteins (IGFBPs) and act on growing bones [9]. ...
... IGFs are bound to circulating binding proteins (IGFBPs) and act on growing bones [9]. Hypersecretion of GH causes gigantism in children and acromegaly in adults, while hyposecretion of GH causes pituitary dwarfism in children and adult GH deficiency (AGHD) in adults [8]. GH and IGF-1 levels are associated with musculotendinous collagen expression [10]. ...
... Hypersecretion of GH results in connective tissue hyperplasia [7]. Thus, hypersecretion of these hormones may affect every part of the musculoskeletal system; it may cause neck and back pain and can mimic rheumatological disorders with joint involvement and morning stiffness [8,11]. This condition is caused by the disproportional enlargement of joint cartilage and increased deposition of fibrous tissue and fat in the synovium [8,12]. ...
Background
Growth hormone deficiency is a well-known clinical entity that is usually treated with somatotropin (growth hormone). Growth hormone has some frequent side effects such as intracranial hypertension, lymphedema and diabetes mellitus.
Case presentation
We report the case of a 14-year-old girl with a history of wrist pain and clumsiness. Magnetic resonance imaging revealed de Quervain tenosynovitis. The patient had a history of using growth hormones for 12 months. We conservatively managed the patient with corticosteroid injections and oral nonsteroidal anti-inflammatory drugs and followed the course. However, the conservative treatment methods failed, and we recommended surgery, which was rejected. She was given nonsteroidal anti-inflammatory drugs and was followed up for 2 years, at the end of which her visual analog scale had decreased from 80 to 50.
Conclusions
To the best of our knowledge this is the first case of de Quervain tenosynovitis related to somatotropin treatment. Physicians should consider the possibility of musculoskeletal side effects after somatotropin treatment.
... Serotonin plays an important role in the process of deep sleep, central and peripheral mechanisms of pain. In favour of the hypothesis of central serotonin deficiency may serve as evidence of declining transportation of its predecessor – tryptophan and reducing its metabolite 5-hydroxyindole acetic acid in the blood plasma of patients with fibromyalgia[Suleymanova G.P., et al., 2011;Tabeeva G.R., et al., 2000;Bennett R.M., 2004;Blotman F., Branco J., 2007]. The role of various neurotransmitters in the pathogenesis of FM are simultaneously involved in modulating pain mechanisms and in the regulation of sleep (norepinephrine, dopamine, histamine, GABA, and others.)[Russel ...
Pain is a concept that is clinically and pathogenetically complex and heterogeneous. It varies in intensity, localization and subjective manifestations (shooting, pressing, pulsating, pricking, cutting, aching, etc.), can be permanent or periodic, which is largely due to localization and what causes it.
Some well-recognised types of pain include muscle or joint-muscle pain. An example of this type of pain is fibromyalgia, a rheumatic disease of unknown etiology, is characterized by generalized muscle
weakness and painful palpation in limited areas of the body, designated as trigger points. Effective methods
of treatment of patients with this disease have not yet been developed. Some medications allow the patient some form of short-term relief, however, even this is not always the case.
Using a complex approach, which involves a wide range of laser therapy methods, it allows the human body to restore itself and any abnormalities in the functioning of various organs and systems, which, as well as providing direct analgesia, ensures the elimination of the causes of the disease. In addition, laser
therapy methods are simple and safe, and unlike analgesics do not cause side effects, as well as there
being no contraindications.
Laser illumination doesn’t only affect one link of the painful reception, but essentially the whole hierarchy of mechanisms in the appearance of pain. Due to this, the curative effect persists for a long period of time. This “versatility” predetermines the exceptional effectiveness of laser therapy, all while using adequate techniques and appropriate equipment. Laser therapeutic devices in the LASMIK series have a frequency of up to 10.000Hz, and a unique set of laser emitting attachments and nozzles. These are the most suitable for implementing methods of pain management.
The book is intended for specialists in rehabilitation, rheumatologists, traumatologists, general practitioners
and physiotherapists.
... Thereafter, the rhGH dose was increased to 0.3 mg to keep the IGF-1 levels above the mean but within the normal range (i.e. effective treatment) as suggested by Bennett 15 and Ahmad et al. 16 ...
During recent decades, the increasing use of opioids for chronic non-cancer pain has raised concerns regarding tolerance, addiction, and importantly cognitive dysfunction. Current research suggests that the somatotrophic axis could play an important role in cognitive function. Administration of growth hormone (GH) to GH-deficient humans and experimental animals has been shown to result in significant improvements in cognitive capacity. In this report, a patient with cognitive disabilities resulting from chronic treatment with opioids for neuropathic pain received recombinant human growth hormone (rhGH) replacement therapy. A 61-year-old man presented with severe cognitive dysfunction after long-term methadone treatment for intercostal neuralgia and was diagnosed with GH insufficiency by GH releasing hormone-arginine testing. The effect of rhGH replacement therapy on his cognitive capacity and quality of life was investigated. The hippocampal volume was measured using magnetic resonance imaging, and the ratios of the major metabolites were calculated using proton magnetic resonance spectroscopy. Cognitive testing revealed significant improvements in visuospatial cognitive function after rhGH. The hippocampal volume remained unchanged. In the right hippocampus, the N-acetylaspartate/creatine ratio (reflecting nerve cell function) was initially low but increased significantly during rhGH treatment, as did subjective cognitive, physical and emotional functioning. This case report indicates that rhGH replacement therapy could improve cognitive behaviour and well-being, as well as hippocampal metabolism and functioning in opioid-treated patients with chronic pain. The idea that GH could affect brain function and repair disabilities induced by long-term exposure to opioid analgesia is supported.
... and loss of muscle quality. Other complications associated with fibromyalgia include reduced resting metabolic rate, [116] under-secretion of growth hormone, [117] reduced bone mineral density (BMD), [118] slowing of gastrointestinal transit [119] and a decline in physical activity. [120] This decline in physical activity alone may produce a variety of other adverse effects, including functional declines that lead to loss in quality of life (QOL) and in the performance of activities of daily living. ...
Strength training (ST) has long been considered a promising intervention for reversing the loss of muscle function and the deterioration of muscle structure associated with advanced age but, until recently, the evidence was insufficient to support its role in the prevention or treatment of disease. In recent decades, there has been a long list of quality reviews examining the effects of ST on functional abilities and a few on risk factors for specific diseases, but none have provided a comprehensive assessment of ST as an intervention for a broad range of diseases. This review provides an overview of research addressing the effectiveness of ST as an intervention for the prevention or treatment of the adverse consequences of (i) aging muscle; (ii) the metabolic syndrome (MetS) and its components, i.e. insulin resistance, abdominal obesity, hyperlipidaemia and hypertension; (iii) fibromyalgia; (iv) rheumatoid arthritis; and (v) Alzheimer's disease. Collectively, these studies indicate that ST may serve as an effective countermeasure to some of the adverse consequences of the MetS, fibromyalgia and rheumatoid arthritis. Evidence in support of the hypothesis that ST reduces insulin resistance or improves insulin action comes both from indirect biomarkers, such as glycosylated haemoglobin (HbA(1c)), and insulin responses to oral glucose tolerance tests, as well as from more direct procedures such as hyperglycaemic and hyperinsulinaemic-euglycaemic clamp techniques. The evidence for the use of ST as a countermeasure of abdominal obesity is less convincing. Although some reports show statistically significant reductions in visceral fat, it is unclear if the magnitude of these changes are physiologically meaningful and if they are independent of dietary influences. The efficacy of ST as an intervention for reducing dyslipidaemia is at best inconsistent, particularly when compared with other pharmacological and non-pharmacological interventions, such as aerobic exercise training. However, there is more consistent evidence for the effectiveness of ST in reducing triglyceride levels. This finding could have clinical significance, given that elevated triglyceride is one of the five criterion measures for the diagnosis of the MetS. Small to moderate reductions in resting and exercise blood pressure have been reported with some indication that this effect may be genotype dependent. ST improves or reverses some of the adverse effects of fibromyalgia and rheumatoid arthritis, particularly pain, inflammation, muscle weakness and fatigue. Investigations are needed to determine how these effects compare with those elicited from aerobic exercise training and/or standard treatments. There is no evidence that ST can reverse any of the major biological or behavioural outcomes of Alzheimer's disease, but there is evidence that the prevalence of this disease is inversely associated with muscle mass and strength. Some indicators of cognitive function may also improve with ST. Thus, ST is an effective countermeasure for some of the adverse effects experienced by patients of many chronic diseases, as discussed in this review.
... Disproportionate growth of musculoskeletal tissue is a major cause of morbidity in patients with acromegaly and GH deficiency (GHD) (1,2), and symptoms from bone, joints, tendon and muscle have a major impact on the quality of life in both patient groups (3)(4)(5)(6). GH and insulin-like growth factor 1 (IGF1) play an important role in the regulation of protein synthesis, including collagen and myofibrillar protein, the two most abundant proteins in musculoskeletal tissues. However, the possible effect of altered GH/IGF1 levels on the synthesis of collagen and myofibrillar protein has not been determined locally in musculoskeletal tissues in patients with acromegaly and GHD. ...
Disproportionate growth of musculoskeletal tissue is a major cause of morbidity in both acromegalic (ACRO) and GH-deficient (GHD) patients. GH/IGF1 is likely to play an important role in the regulation of tendon and muscle collagen. We hypothesized that the local production of collagen is associated with the level of GH/IGF1.
As primary outcomes, collagen mRNA expression and collagen protein fractional synthesis rate (FSR) were determined locally in skeletal muscle and tendon in nine ACRO and nine GHD patients. Moreover, muscle myofibrillar protein synthesis and tendon collagen morphology were determined.
Muscle collagen I and III mRNA expression was higher in ACRO patients versus GHD patients (P<0.05), whereas collagen protein FSR did not differ significantly between ACRO and GHD patients in muscle (P=0.21) and tendon (P=0.15). IGF1Ea and IGF1Ec mRNA expression in muscle was higher in ACRO patients versus GHD patients (P<0.01). Muscle IGF1Ea mRNA expression correlated positively with collagen I mRNA expression (P<0.01). Tendon collagen fibrillar area tended to be higher in GHD patients relative to ACRO patients (P=0.07). Thus, we observed a higher expression for collagen and IGF1 mRNA in local musculotendinous tissue in ACRO patients relative to GHD patients. Moreover, there was a tendency towards a higher collagen protein FSR and a smaller collagen fibril diameter in ACRO patients relative to GHD patients. The results indicate a collagen-stimulating role of local IGF1 in human connective tissue and add to the understanding of musculoskeletal pathology in patients with either high or low GH/IGF1 axis activity.
