Pain
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Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (eg, depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. ⋯ Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all 3 groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes.
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Treatment of severe pain by morphine, the gold-standard opioid and a potent drug in our arsenal of analgesic medications, is limited by the eventual development of hyperalgesia and analgesic tolerance. We recently reported that systemic administration of a peroxynitrite (PN) decomposition catalyst (PNDC) or superoxide dismutase mimetic attenuates morphine hyperalgesia and antinociceptive tolerance and reduces PN-mediated mitochondrial nitroxidative stress in the spinal cord. These results suggest the potential involvement of spinal PN signaling in this setting; which was examined in the present study. ⋯ Additionally, intrathecal MnTnHex-2-PyP(5+) attenuated neuroimmune activation by preventing the activation of nuclear factor kappa B, extracellular-signal-regulated kinase and p38 mitogen activated protein kinases, and the enhanced levels of proinflammatory cytokines, interleukin (IL)-1β and IL-6, while increasing anti-inflammatory cytokines, IL-4 and IL-10. The role of PN was further confirmed using intrathecal or oral delivery of the superoxide-sparing PNDC, SRI-110. These results suggest that mitochondrial-derived PN triggers the activation of several biochemical pathways engaged in the development of neuroinflammation in the spinal cord that are critical to morphine hyperalgesia and tolerance, further supporting the potential of targeting PN as an adjunct to opiates to maintain pain relief.
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Randomized Controlled Trial Multicenter Study
Efficacy and safety of tanezumab versus naproxen in the treatment of chronic low back pain.
Tanezumab is a humanized monoclonal antibody that specifically inhibits nerve growth factor as a treatment for chronic pain. This phase IIB study investigated the efficacy and safety of tanezumab for chronic low back pain vs placebo and naproxen. Patients (N=1347) received intravenous tanezumab (5, 10, or 20mg every 8weeks), naproxen (500mg twice daily), or placebo. ⋯ The most frequently reported adverse events resulting in discontinuation of tanezumab treatment were arthralgia and paresthesia; the highest frequency was observed with tanezumab 20mg (both 1.4%). Serious adverse event incidence was similar across treatments. In conclusion, tanezumab provided significantly greater improvement in pain, function, and global scores vs placebo and naproxen in patients with chronic low back pain.
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The development of valid and informative treatment risk-benefit profiles requires consistent and thorough information about adverse event (AE) assessment and participants' AEs during randomized controlled trials (RCTs). Despite a 2004 extension of the Consolidated Standards of Reporting Trials (CONSORT) statement recommending the specific AE information that investigators should report, there is little evidence that analgesic RCTs adequately adhere to these recommendations. This systematic review builds on prior recommendations by describing a comprehensive checklist for AE reporting developed to capture clinically important AE information. ⋯ Trials of participants with acute or chronic pain conditions and industry-sponsored trials typically provided more and better-quality AE data than trials involving pain-free volunteers or trials that were not industry sponsored. The results of this review suggest that improved AE reporting is needed in analgesic RCTs. We developed an ACTTION (Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks) AE reporting checklist that is intended to assist investigators in thoroughly and consistently capturing and reporting these critically important data in publications.
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Comparative Study Controlled Clinical Trial
Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain.
Central sensitization and dysregulation of peripheral substance P and neurokinin-1 receptor (NK-1R) signaling are associated with chronic abdominal pain in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Although positron emission tomography (PET) has demonstrated that patients with injury-related chronic pain have diminished NK-1R availability in the brain, it is unknown whether these deficits are present in IBD and IBS patients, who have etiologically distinct forms of non-injury-related chronic pain. This study's aim was to determine if patients with IBD or IBS exhibit deficits in brain expression of NK-1Rs relative to healthy controls (HCs), the extent to which expression patterns differ across patient populations, and if these patterns differentially relate to clinical parameters. ⋯ BP in a subset of these regions was robustly related to discrete clinical parameters in each patient population. Widespread deficits in NK-1R BP occur in IBD and, to a lesser extent, IBS; however, discrete clinical parameters relate to NK-1R BP in each patient population. This suggests that potential pharmacological interventions that target NK-1R signaling may be most effective for treating distinct symptoms in IBD and IBS.