The journal of pain : official journal of the American Pain Society
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A rat model of neuropathic pain at 6 weeks after spinal nerve ligation (SNL6w) exhibits both mechanical hypersensitivity and impaired noxious stimuli-induced analgesia (NSIA). Repeated treatment with antidepressants can produce antihypersensitivity and restore NSIA. To examine the involvement of a brain-derived neurotrophic factor-mediated mechanism, a tropomyosin receptor kinase B (TrkB) agonist, 7,8-dihydroxyflavone (DHF), was administered to SNL6w rats (5 mg/kg/d for 5 days). ⋯ PERSPECTIVE: This article demonstrates that repeated treatment with TrkB agonist, DHF, restored endogenous analgesia. Repeated amitriptyline treatment showed similar effect via TrkB-mediated mechanisms, and the effect may be independent from the effect of antihypersensitivity. This effect of TrkB activation is promising for patients with chronic pain with impaired descending inhibition.
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It is generally assumed that individuals exhibiting high pain inhibition also tend to exhibit low pain facilitation, but little research has examined this association in individuals with pain. The aims of this cross-sectional study were 1) to examine the association between measures of conditioned pain modulation (CPM) and temporal summation (TS) in individuals with chronic pain, and 2) to examine whether this association was moderated by demographic (age, sex), psychological (depression, catastrophizing), or medication-related (opioid use) variables. Individuals (N= 190) with back or neck pain completed questionnaires and underwent a series of quantitative sensory testing procedures assessing CPM and TS. ⋯ The magnitude of CPM was lower for opioid users than nonusers, suggesting that opioid use might dampen the functioning of endogenous pain-inhibitory systems and possibly contribute to a discordance between measures of pain inhibition and pain facilitation. PERSPECTIVE: Results of the present study indicated that greater endogenous pain-inhibitory capacity is associated with lower levels of pain facilitation. This association, however, was not significant among opioid users, suggesting that opioids might compromise the functioning and interrelationship between endogenous pain modulatory systems.
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An important predictor of opioid overdose is co-use of benzodiazepines, which are often prescribed for anxiety. Coping with anxiety may be particularly difficult among individuals with a history of abuse, as it is often linked to higher pain severity and poorer coping skills. We explored whether abuse history moderated the association between anxiety and benzodiazepine use among current opioid users. ⋯ Providers should be aware of life history factors, including abuse, that may drive the need for medication. Perspective: This article examines the association between history of abuse victimization and co-use of benzodiazepines among chronic pain patients reporting current opioid use. The findings suggest that cumulative victimization across the lifespan may contribute to co-use by increasing sensitivity to psychological or physical distress or by negatively impacting coping skills.
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Randomized Controlled Trial Multicenter Study
Fulranumab as Adjunctive Therapy for Cancer-Related Pain: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study.
This randomized, double-blind (DB), placebo-controlled, phase 2 study assessed the efficacy and safety of fulranumab as a pain therapy adjunctive to opioids in terminally ill cancer patients. Ninety-eight patients were randomized (2:1) to receive one subcutaneous injection of fulranumab (9 mg) or placebo in the 4-week DB phase. Seventy-one (72%) patients entered the 48-week open-label extension phase and were administered 9 mg of fulranumab every 4 weeks. ⋯ Although no differences were seen between fulranumab and placebo groups on the primary endpoint, improvements in BPI-SF pain subscale scores and responder rates support further research of anti-nerve growth factor therapy in cancer-related pain. PERSPECTIVE: Efficacy and safety of fulranumab as adjunctive pain therapy in terminally ill cancer patients were assessed. Results suggest that anti-NGF agents may prove to be novel additions in helping to optimize pain relief in cancer patients who fail to respond adequately to opioids and other common co-analgesics.
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Fewer randomized clinical trials (RCTs) are conducted for chronic or recurrent pain in pediatric populations compared with adult populations; thus, data to support treatment efficacy in children are limited. This article evaluates the design features and reporting practices of RCTs for chronic and recurrent pain that are likely unique to, or particularly important in, a pediatric population to promote improvements in the evidence base for pediatric pain treatments. Areas covered include outcome measure selection and reporting and reporting of adverse events and challenges to recruitment and retention. ⋯ The goal of this article is to promote comprehensive reporting of pediatric pain RCTs to improve the design of future trials, facilitate conduction of systematic reviews and meta-analyses, and better inform clinical practice. PERSPECTIVE: This review of chronic and recurrent pediatric pain trials demonstrates inadequacies in the reporting quality of key features specifically important to pediatric populations. It provides recommendations that address these shortcomings to promote continued efforts toward improving the quality of the design and publication of future pediatric clinical pain trials.