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Successful treatment of chronic pain for patients with failed back surgery syndrome can be extremely complicated. These patients require careful and individualized clinical assessment, as they often present with mixed pain syndromes that involve both neuropathic and nociceptive components. The distinct types of pain involved in such cases may requi...
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Spinal cord stimulation (SCS) is an alternative or adjunct therapy to treat chronic pain, a prevalent and clinically challenging condition. Although SCS has substantial clinical success, the therapy is still prone to failures, including lead breakage, lead migration, and poor pain relief. The goal of this study was to develop a computational model...
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... Thus, neuropathic pain is a chronic pain state that can involve both inflammatory and neuropathic components [5]. Due to the multifactorial pathophysiology of neuropathic pain, most of the existing single-target monotherapy approaches are inadequate for its treatment [6]. Combination therapies using analgesics with different mechanisms of action [7] are becoming increasingly popular for its therapeutic management [8,9]. ...
... Two-way ANOVA followed by Tukey's multiple comparisons post-hoc test showed a significant effect of time (F (3,135) = 187.22), treatment (F (6,45) = 22.39) and a significant interaction time X treatment (F (18,135) = 9.50), on mechanical hyperalgesia in CCI rats. ...
... Two-way ANOVA followed by Tukey's multiple comparisons post-hoc test showed a significant effect of time (F (3,135) = 76.97), treatment (F (6,45) = 36.95) and a significant interaction time X treatment (F (18,135) = 7.79), on thermal hyperalgesia in CCI rats. ...
Chronic pain is an enormous public health concern, and its treatment is still an unmet medical need. Starting from data highlighting the promising effects of some nonsteroidal anti-inflammatory drugs in combination with gabapentin in pain treatment, we sought to combine ketoprofen lysine salt (KLS) and gabapentin to obtain an effective multimodal therapeutic approach for chronic pain. Using relevant in vitro models, we first demonstrated that KLS and gabapentin have supra-additive effects in modulating key pathways in neuropathic pain and gastric mucosal damage. To leverage these supra-additive effects, we then chemically combined the two drugs via co-crystallization to yield a new compound, a ternary drug-drug co-crystal of ketoprofen, lysine and gabapentin (KLS-GABA co-crystal). Physicochemical, biodistribution and pharmacokinetic studies showed that within the co-crystal, ketoprofen reaches an increased gastrointestinal solubility and permeability, as well as a higher systemic exposure in vivo compared to KLS alone or in combination with gabapentin, while both the constituent drugs have increased central nervous system permeation. These unique characteristics led to striking, synergistic anti-nociceptive and anti-inflammatory effects of KLS-GABA co-crystal, as well as significantly reduced spinal neuroinflammation, in translational inflammatory and neuropathic pain rat models, suggesting that the synergistic therapeutic effects of the constituent drugs are further boosted by the co-crystallization. Notably, while strengthening the therapeutic effects of ketoprofen, KLS-GABA co-crystal showed remarkable gastrointestinal tolerability in both inflammatory and chronic neuropathic pain rat models. In conclusion, these results allow us to propose KLS-GABA co-crystal as a new drug candidate with high potential clinical benefit-to-risk ratio for chronic pain treatment.
... It is very likely that two or more neuromodulation systems could have a synergic effect [50,67]. The same way that neurostimulator devices are becoming smaller, long-lasting and rechargeable, electrodes are also becoming easier to implant, with multiple contact lines available [68]. In addition, the software and options of stimulation are becoming very sophisticated and precise. ...
Background and objectives: The management of complex regional pain syndrome (CRPS) remains a challenging task therefore a large number of interventions have been investigated. Lately, invasive and non-invasive neuromodulation have been coming up as an alternative for some patients even as an add-on treatment to medicines or physical therapy. The objective of this review is to evaluate the evidence of its effectiveness in CRPS chronic pain management.
Methods: We have used key words referring to neuromodulation techniques and CRPS to select studies from Medline, Lilacs and Cochrane Library databases. All relevant articles which have described any kind of neuromodulation as CRPS primary treatment have been reviewed by two independent researchers to assign the level of evidence according to Oxford Level of Evidence. A third researcher was consulted in dubious cases to get to the final conclusion.
Results: Although a variety of methods and devices have been used, the evidences are still poor. There is no level 1 study which confers grade A of recommendation for any method of neuromodulation in the CRPS treatment. Repetitive transcranial magnetic stimulation (rTMS) over the motor cortex and spinal cord stimulation (SCS) were the techniques with the best grade of recommendation (B or C).
Conclusion: The literature still lacks high-quality evidence supporting neuromodulation effectiveness in CRPS pain treatment. We found only a few studies that had approached this issue properly. Those facts themselves were the main limitation of this study and of those that must be coming soon. High-quality multicentre trials ought to be performed for definitive conclusions.
Deep brain stimulation (DBS) is increasing in popularity due to its successful treatment of movement disorders and its relatively low risk profile. However, its use for refractory, chronic pain syndromes actually precedes its use in movement disorders. Although the precise mechanism remains unknown, both neuropathic and nociceptive pain have been successfully treated with DBS with some studies noting greater success with nociceptive pain in particular. Common targets for the treatment of pain utilizing DBS include the periventricular/periaqueductal gray area (PVG/PAG); sensory thalamus, particularly the ventral posterolateral/medial nucleus (VPL/VPM); anterior cingulate cortex (ACC); posterior hypothalamus (PH); center median-parafascicular (CM-Pf) complex; and internal capsule. Targets are typically chosen on the basis of clinical presentation, with some studies suggesting coverage of multiple targets in order to ensure relief of complex pain syndromes. Additional research is necessary to uncover mechanism of action, proper stimulation targets, and efficacy of the DBS therapy.
Deep brain stimulation (DBS) is a form of intracranial stimulation in which electrical current can be delivered to deep nuclei. It is performed by the insertion of implanted electrodes via a burrhole to the subcortical targets, utilizing navigation. It is a reversible and adjustable procedure that falls under the category of neuromodulation; because it is less invasive than other neurosurgical procedures, it carries a low risk profile.
Deep brain stimulation (DBS) has been used off-label to treat chronic, neuropathic, or nociceptive pain for decades; however, the precise mechanism of action remains elusive. In the absence of a standardized treatment algorithm, targets are determined based on the characteristics of pain presentation. The majority of studies to date have been case series focusing on stimulation of the sensory thalamus (ST) and periventricular/periaqueductal gray area (PVG/PAG) to successfully treat a wide range of chronic pain conditions, although several other deep brain structures have also been targeted. The treatment is associated with a relatively low-risk profile, with intracranial hemorrhage being the most potentially serious adverse event. Further research is necessary to better understand a number of issues, including the relationships between pathophysiology and mechanism of action, as well as optimal stimulation targets and parameters.
Objectives:
To assess the value of the concept of mixed pain by investigating its acceptance and interpretation by health care professionals and the differential characteristics in patients with mixed pain.
Materials and methods:
Data from 5024 patients suffering pain from 551 sites in Primary Care and Orthopedics settings were analyzed in this cross-sectional study. Pain characteristics, other factors influencing pain, health care-related data and health-related quality of life were summarized and compared among 3 groups of patients according to the type of pain (nociceptive, neuropathic, or mixed), as assigned by the investigators after considering the pathophysiological mechanisms involved.
Results:
Pain was of mixed pathophysiology in most patients (59.3%; 95% confidence interval [CI], 59.2%-59.5%), followed by nociceptive (31.8%; 95% CI, 31.6%-32.0%) and neuropathic pathophysiology (8.9%; 95% CI, 8.8%-9.1%). Patients with mixed pain had pain in >1 site more frequently than the other groups. Spinal conditions was the attributed cause of pain in >80% of patients with mixed pain, whereas nonspinal osteoarthritis represented almost a third. Patients with mixed pain showed a greater clinical complexity than the remaining patients, as they reflected: more comorbidities, adverse psycho-social factors, health care resource utilization, undertreatment, and perceived difficulties in patient management, but less perceived effectiveness of treatments and a lower health-related quality of life.
Discussion:
An independent category in the pathophysiological classification of pain is justified based on the differential characteristics of patients with mixed pain, although conceptualization of mixed pain should be improved. Increasing referrals to other specialists or implementing chronic pain management programs would seem advisable.
Conclusions:
Patients with mixed pain showed more clinical complexity than patients with other types of pain. The consideration of mixed pain as an independent pathophysiological category may be justifiable on empirical clinical grounds.
Background:
. Intrathecal (IT) pumps have become a valuable tool in managing intractable non-cancer pain. The purpose of this study was to evaluate the efficacy of using a rigorous treatment algorithm for trialing and implanting IT pumps with hydromorphone and bupivacaine in managing a more homogeneous population of post-laminectomy syndrome or failed back surgery syndrome (FBSS) patients.
Methods:
. This is a retrospective analysis of FBSS patients with chronic intractable back pain implanted with IT pumps delivering hydromorphone and bupivacaine.
Results:
. A cohort of 57 (26 males, 31 females) consecutively implanted FBSS patients was analyzed. The average age at implant was 65.4 years. Average pain scores were 8.4 ± 0.2 (pre-implant), 4.9 ± 0.4 (6 months), 5.2 ± 0.5 (12 months), and 4.3 ± 0.5 (24 months). Average oral opioid doses in morphine equivalents were 56 ± 10 mg/day (pre-implant), 12.0 ± 3.5 mg/day (12 months), 15 ± 6 mg/day (24 months). Average IT hydromorphone doses were 79 ± 6.8 mcg/day (at implant), 184 ± 22 mcg/day (6 months), 329 ± 48 mcg/day (12 months), and 487 ± 80 mcg (24 months). IT hydromorphone dose escalation from baseline was 133% (6 months vs baseline), 78% (12 months vs 6 months), and 48% from 12 months to 24 months. Average IT bupivacaine doses were 5.8 ± 0.3 mg/day (implant), 9.5 ± 0.6 mg/day (6 months), 12.2 ± 0.7 mg/day (12 months), and 12.6 ± 0.9 mg/day (24 months).
Conclusion:
. IT hydromorphone and bupivacaine are effective in treating chronic pain of FBSS, as demonstrated by the reduction of pain intensity and oral opioid consumption. However, an IT dose escalation phenomenon was observed, although at a reduced rate compared with what had been previously reported in the literature. It is possible that the local anesthetic combination delivered via a patient-activaed bolus device is an important factor. Despite demonstrating effectiveness, the clinical utility of myPTM-optimized IT therapy remains limited by a lack of prospective, placebo-controlled trials and comparative effectiveness research.
Deep brain stimulation (DBS) is a commonly performed procedure and has been used for the treatment of chronic pain since the early 1970s. A review of the literature was performed utilizing the PubMed database evaluating the use of DBS in the treatment of various pain syndromes. Literature over the last 30 years was included with a focus on those articles in the last 10 years dealing with pain conditions with the highest success as well as the targets utilized for treatment. DBS carries favorable results for the treatment of chronic pain, especially when other methods have not been successful such as medications, conservative measures, and extracranial procedures. Various chronic pain conditions reported in the literature respond to DBS including failed back surgery syndrome (FBSS), phantom limb pain, and peripheral neuropathic pain with a higher response rate for those with nociceptive pain compared to neuropathic pain. Cephaligias have promising results, with cluster headaches carrying the best success rates. DBS plays a role in the treatment of chronic pain conditions. Although considered investigational in the USA, it carries promising success rates in a recalcitrant patient population.
The objective of this case report is to describe the use of in situ spinal cord stimulator (SCS) for postthoracotomy pain syndrome (PTPS). We report a 39-year-old woman with complex regional pain syndrome type I of the left lower extremity. The patient's pain was relieved by a SCS for 1 month before the patient developed slipping rib syndrome at her T12 rib from an unrelated trauma. After failed conservative treatments and undergoing a thoracotomy procedure, the patient developed PTPS. Conservative management with medications and intercostal nerve blocks provided short-term relief. An already implanted single Octrode with Eon Mini generator (St Jude Neuromodulator, Plano, TX) at the T7 level was reprogrammed in attempt to recruit peripheral fibers to target the patient's additional areas of chest discomfort. This adjustment improved the pain at the left lateral rib area as well as her left leg. The patient was followed for 1 year, and her quality of life improved since her initial presenting symptoms. The use of the SCS in this patient provided significant lasting pain relief for both complex regional pain syndrome and PTPS. We believe that the use of SCS should be considered as a treatment option for patients with PTPS to avoid side effects associated with medications and to provide long-term pain relief.
Copyright © 2015. Published by Elsevier Inc.
Our objective is to analyze and observe the different administration routes of parecoxib sodium pretreatment on the behavioral improvement of rats with neuropathic pain to provide the preclinical data of parecoxib sodium on neuropathic pain treatment. 30 SD rats were randomly divided into five groups, including model group, sham operation group, intrathecal injection group (IT group), intraperitoneal injection group (IP group), and perineural infiltration group (PI group). The rats in model group and three parecoxib sodium pretreatment groups received spinal nerve ligation (SNL). Heat pain test and 50 % paw mechanical withdrawal threshold test (50 % PMWT) were use to assess the responses after parecoxib sodium pretreatment. 50 % PMWT results of right foot in five groups had no statistical difference (P > 0.05); 50 % PMWT results of left and right feet in three parecoxib sodium pretreatment groups were obviously higher than SNL group at different time points, which was statistically different (P < 0.05); in comparison with three pretreatment groups, the data of left foot in IT group were obviously higher than PI group and IP group, and the comparison among three groups had significant difference (P < 0.05). However, the data of right foot had no significant difference among three groups (P > 0.05). Paw thermal withdrawal latency (PTWL) results of left and right feet in five groups had no significant difference before surgery (P > 0.05); after the establishment of neuropathic model, PTWL results in five groups were significantly decreased; however, PTWL results of left and right feet at 3 days after surgery in IT group were significantly higher than the two other pretreatment groups (P < 0.05); PTWL results of left and right feet at 7 and 14 days after surgery had no significant difference. Parecoxib sodium pretreatment can effectively improve the behaviors caused by neuropathic pain, and intrathecal injection is the most effective route of administration.
