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Small-fiber polyneuropathy involves preferential damage to the thinly myelinated A-delta fibers, unmyelinated C sensory fibers, or autonomic or trophic fibers. Although this condition is common, most patients still remain undiagnosed and untreated because of lagging medical and public awareness of research advances. Chronic bilateral neuropathic pain, fatigue, and nausea are cardinal symptoms that can cause disability and dependence, including pain medication dependence.
Learn More >The current review addresses one of the most common neurological disorders, diabetic polyneuropathy (DPN). DPN is debilitating, irreversible and dwarfs the prevalence of most other chronic disorders of the nervous system. Its complications include foot ulceration, amputation, falling and intractable neuropathic pain. Moreover, tight control of hyperglycemia reduces the incidence of DPN in type 1 diabetes mellitus but its role in type 2 diabetes mellitus is less clear.
Learn More >Opioid use disorders (OUDs) are diseases of the brain with behavioral, psychological, neurobiological, and medical manifestations. Vulnerability to OUDs can be affected by factors such as genetic background, environment, stress, and prolonged exposure to μ-opioid agonists for analgesia. Two standard-of-care maintenance medications, methadone and buprenorphine-naloxone, have a long-term positive influence on health of persons with opioid addiction. Buprenorphine and another medication, naltrexone, have also been approved for administration as monthly depot injections. However, neither medication is used as widely as needed, due largely to stigma, insufficient medical education or training, inadequate resources, and inadequate access to treatment. Ongoing directions in the field include (i) personalized approaches leveraging genetic factors for prediction of OUD vulnerability and prognosis, or for targeted pharmacotherapy, and (ii) development of novel analgesic medicines with new neurobiological targets with reduced abuse potential, reduced toxicity, and improved effectiveness, especially for chronic pain states other than cancer pain.
Learn More >Research on chronic pain has traditionally focused on how direct pain experiences lead to maladaptive thoughts, feelings, and actions which set the stage for, and maintain, pain-related disability. Yet the capacity for language (and more specifically verbal instructions or rules) to put people into indirect contact with pain has never been systematically investigated. In this paper we introduce a novel theoretical perspective on verbal processes and discuss how the study of verbal rules may increase our understanding of both maladaptive and adaptive functioning in chronic pain. Several useful characteristics of verbal rules and rule-following in the context of chronic pain are outlined. Future research directions and implications for clinical practice are then discussed. Perspective: This focus article argues that by studying verbal rules and rule-following we will gain a better understanding of (mal)adaptive functioning in the context of chronic pain. Future research directions are outlined and suggestions for improving clinical practice are considered.
Learn More >Although opioids and pregabalin are widely used for cancer-related neuropathic pain (CNP), no clinical trials exist to determine which medications are effective when an opioid-pregabalin combination therapy fails.
Learn More >Acute and persistent pain are recognized consequences of TBI that can enhance suffering and significantly impair rehabilitative efforts. Both experimental models and clinical studies suggest that TBI may result in an imbalance between descending pain facilitatory and inhibitory pathways. The aim of this study was to assess the role of enhanced descending serotonin-mediated pain facilitation in a rat TBI model using selective spinal serotonergic fiber depletion with 5, 7-dihydroxytryptamine (DHT). We observed significant hindpaw allodynia in TBI rats that was reduced after DHT but not vehicle treatment. Immunohistochemical studies demonstrated profound spinal serotonin depletion in DHT-treated rats. Furthermore, lumbar intrathecal administration of the 5-HT receptor antagonist ondansetron at 7 days post-injury (DPI), when hindpaw allodynia was maximal, also attenuated nociceptive sensitization. Additional immunohistochemical analyses of the lumbar spinal cord at 7 DPI revealed a robust bilateral microglial response in the superficial dorsal horns that was significantly reduced with DHT treatment. Furthermore, serotonin depletion also prevented the TBI-induced bilateral increase in c-Fos positive cells within the Rexed laminae I and II of the dorsal horns. These results indicate that in the weeks following TBI, pain may be responsive to 5-HT receptor antagonists or other measures which rebalance descending pain modulation.
Learn More >Opioid-induced constipation (OIC) is a common side effect of chronic opioid therapy. Previously, naldemedine, a peripherally acting ì-opioid receptor antagonist demonstrated efficacy in the treatment of OIC. In this exploratory analysis, the onset of action of naldemedine was evaluated in 2 identically designed phase 3, randomized, placebo-controlled trials. Proportion of patients experiencing a spontaneous bowel movement (SBM) within 24 hours of treatment initiation, time from initial dose to first SBM and weekly SBM frequency were assessed. Naldemedine was associated with significant increases in the proportion of patients experiencing an SBM at 4, 8, 12, and 24 hours after the initial dose compared with placebo (all P<0.0001). Within 24 hours in both studies, statistically significantly (P<0.0001) more patients treated with naldemedine compared with placebo experienced an SBM (61.2% vs. 28.3% and 56.5% vs. 33.6%, respectively). Median times to first SBM were significantly shorter in the naldemedine group versus placebo (COMPOSE-1, 16.1 vs. 46.7 hours; COMPOSE- 2, 18.3 vs 45.9 hours; P<0.0001). Naldemedine was also associated with significant increases in weekly SBM frequency versus placebo within 1 week (P<0.001). Most common treatment-emergent adverse event (TEAE) were gastrointestinal-related (abdominal pain, diarrhea, and nausea). TEAEs were reported most frequently on day 1, followed by a decrease from days 2-7. Naldemedine had a timely onset of effect, and gastrointestinal AEs largely resolved within the first week. These findings should assist clinicians counseling patients with chronic noncancer pain on expectations when initiating naldemedine for OIC. ClinicalTrials.gov Registration: NCT01965158 and NCT01993940This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Learn More >Sleep problems are common for individuals living with physical disabilities and chronic pain. However, the factors that influence the relationship between pain and sleep problems in these populations remain unknown.
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