Pain medicine : the official journal of the American Academy of Pain Medicine
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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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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.
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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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Although both gabapentin and pregabalin are first-line drugs for neuropathic pain including postherpetic neuralgia (PHN), no report has directly compared the magnitude of pain relief and the incidence of side effects of both drugs. By substituting gabapentin with pregabalin in postherpetic neuralgia therapy, we can compare the two drugs. ⋯ It was suggested that the analgesic action of pregabalin in PHN was six times that of gabapentin in terms of effectiveness in dosage conversion. Regarding the side effects, although the incidence of the peripheral edema was higher with pregabalin compared with gabapentin, this finding is not conclusive because the present study was conducted in a small number of subjects. Although pain reduction can be expected to increase with pregabalin dosage, it is necessary to increase the dosage gradually and carefully because of exacerbation of side effects.