Pain medicine : the official journal of the American Academy of Pain Medicine
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Review
The roles of sodium channels in nociception: implications for mechanisms of neuropathic pain.
Animal models have provided useful insights into the development and treatment of neuropathic pain. New genetic data from both human studies and transgenic mouse models suggest that specific voltage-gated sodium channel subtypes are associated with specific types of pain and, as such, may be useful analgesic drug targets for a variety of pain types including neuropathic pain. Global voltage-gated sodium channel blockers such as lidocaine have proven efficacy in treating pain but can be limited by adverse effects when administered systemically. ⋯ Nav1.7 is a useful target for ameliorating acute mechanical pain and inflammatory pain, and strong evidence also suggests that Nav1.9 could be targeted for treating inflammatory pain. Selective blockers of Nav1.8 could also have clinical benefit for visceral pain. Although there is no association between a single sodium channel isoform and neuropathic pain, combined blockade of peripherally expressed isoforms Nav1.7, Nav1.8, and Nav1.9 may prove useful.
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There has been considerable progress identifying pathophysiologic mechanisms of neuropathic pain, but analgesic medications with improved efficacy, safety, and tolerability still represent an unmet public health need. Numerous treatments examined in recent randomized clinical trials (RCTs) have failed to show efficacy for neuropathic pain, including treatments that had previously demonstrated efficacy. This suggests that at least some negative results reflect limited assay sensitivity of RCTs to distinguish efficacious treatments from placebo. ⋯ The US Food and Drug Administration recently launched the Analgesic Clinical Trial Innovations, Opportunities, and Networks (ACTION) public-private partnership, which is designed to facilitate the discovery and development of analgesics with improved efficacy, safety, and tolerability for acute and chronic pain conditions. ACTION will establish a collaborative effort to prioritize research objectives, develop a standardized analgesic database platform, and conduct methodologically focused studies to increase the assay sensitivity and efficiency of analgesic clinical trials. The results of these activities have the potential to inform and accelerate the development of improved pain management interventions of all types, not just pharmacologic treatments.
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The study aims to highlight the potentially serious consequences of inadvertent soft-tissue injection of intrathecal drugs such as clonidine, during refills of implanted drug delivery devices, and to suggest strategies to reduce this complication. ⋯ Inadvertent soft-tissue injection is possibly an underappreciated and underreported complication of intrathecal analgesia via an implanted drug delivery device. Under some circumstances, large doses of other intrathecal drugs such as bupivacaine, opioids, ziconotide, and baclofen may also be delivered by inadvertent soft-tissue injection with potentially life-threatening consequences. We recommend that practitioners, institutions, and professional bodies who manage patients with intrathecal analgesia via intrathecal drug delivery devices highlight and audit this complication and develop systems to manage it.
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To assess the influence of pain severity, catastrophizing, anger, anxiety, and depression on nonspecific low back pain (LBP)-related disability in Spanish patients with chronic LBP. Study Design. Cross-sectional correlation between psychological variables and disability. Methods. One hundred twenty-three patients treated for chronic LBP in pain units within nine Spanish National Health Service Hospitals, in eight cities, were included in this study. Intensity of LBP and pain referred to the leg, disability, catastrophizing, anger, state anxiety, trait anxiety, and depression were assessed through previously validated questionnaires. The association of disability with these variables, as well as gender, age, academic level, work status, and use of antidepressants, was analyzed through linear regression models. ⋯ Among Spanish chronic LBP patients treated at pain units, the correlation of catastrophizing, state anxiety, anger, and depression with disability ceases to be significant when variations of trait anxiety are taken into account. Further studies with LBP patients should determine whether anxiety trait mediates the effects of the other variables, explore its prognostic value, and assess the therapeutic effect of reducing it.
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Randomized Controlled Trial
Individual differences in morphine and butorphanol analgesia: a laboratory pain study.
Responses to opioid analgesics are highly variable, and the understanding of contributing factors is limited. This laboratory study was designed to examine the contributions of sex and race to inter-individual variability in response to opioids. ⋯ Findings are among the first to demonstrate race differences in a laboratory study of opioid analgesia.