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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Neuropathic pain often imposes a substantial and unrelenting burden on those individuals who have it; single-agent analgesics typically only reduce pain at best. Worldwide, five sets of treatment recommendations offer insight into managing neuropathic pain, including two European guidelines, one Canadian, one Latin American, and another constructed under the auspices of the International Association for the Study of Pain (IASP). ⋯ As the evidence base expands, the addition of new comparative trial data will further refine the development of new guidance for clinical management of neuropathic pain. New alternatives for managing neuropathic pain, such as the high-concentration capsaicin patch, will enlarge the treatment armamentarium and potentially impact therapeutic guidelines.
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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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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.
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Randomized Controlled Trial
Efficacy of gabapentin enacarbil vs placebo in patients with postherpetic neuralgia and a pharmacokinetic comparison with oral gabapentin.
The efficacy of gabapentin in some patients with postherpetic neuralgia (PHN) may be limited by suboptimal drug exposure from unpredictable and saturable absorption. Gabapentin enacarbil (GEn) was designed for absorption by high-capacity transporters expressed throughout the intestine and undergoes rapid postabsorption hydrolysis to gabapentin. GEn extended-release tablets provide sustained, dose-proportional gabapentin exposure. This study assessed the efficacy of GEn vs placebo and compared the pharmacokinetics of gabapentin after oral dosing of GEn or gabapentin in patients with PHN. ⋯ GEn was effective in providing PHN pain relief, improved gabapentin exposure compared with gabapentin capsules, and was generally safe and well tolerated in patients with PHN.