Pain
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Randomized Controlled Trial
Can early oral prolonged-release oxycodone with or without naloxone reduce the duration of epidural analgesia after cystectomy? A 3-arm, randomized, double-blind, placebo-controlled trial.
Thoracic epidural analgesia (TEA) enhances recovery after bowel surgery. Early postoperative prolonged-release oral formulation of oxycodone or oxycodone/naloxone is potentially useful as a second analgesic step to reduce the duration of TEA. We hypothesized that oxycodone would decrease the duration of TEA and combined with naloxone preserve gastrointestinal function. ⋯ In the oxycodone group, we found 8/30 patients with ileus (27%) compared to 2/28 (7%) in the oxycodone/naloxone group and to 2/30 (7%) in the placebo group; (P = 0.031). Oxycodone, with or without naloxone, did not reduce the duration of TEA. Oxycodone alone led to a delayed return of bowel function, whereas the combination was not different from placebo.
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Review
Emerging therapies for neuropathic pain: new molecules or new indications for old treatments?
Neuropathic pain represents a highly unmet medical need because most of the available treatments have a modest efficacy or dose-limiting side effects. Hence, novel therapeutic perspectives are warranted. Many compounds acting on new pain targets are in preclinical or early clinical development. ⋯ Another type of emerging drug therapy in neuropathic pain is represented by drugs largely used for other indications, such as botulinum toxin A and the antiepileptic oxcarbazepine, which have recently found to be effective in peripheral neuropathic pain. Emerging nondrug medical therapy with promising results in neuropathic pain also encompasses noninvasive brain neurostimulation techniques, such as repetitive transcranial magnetic stimulation and transcranial direct electrical stimulation. In this article, we review emerging medical treatments for neuropathic pain that are clinically available or with promising results from clinical trials.
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Diabetic peripheral neuropathy (DPN) is a common disabling complication of diabetes. Almost half of the patients with DPN develop neuropathic pain (NeuP) for which current analgesic treatments are inadequate. Understanding the role of genetic variability in the development of painful DPN is needed for improved understanding of pain pathogenesis for better patient stratification in clinical trials and to target therapy more appropriately. ⋯ Using a structural model of NaV1.7, we were also able to provide further insight into the structural mechanisms underlying fast inactivation and the role of the C-terminal domain in this process. Our observations suggest that rare NaV1.7 variants contribute to the development NeuP in patients with DPN. Their identification should aid understanding of sensory phenotype, patient stratification, and help target treatments effectively.
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Global burden of disease studies measure the impact of disability and premature death resulting from specific diseases and injuries. Recently, these studies have highlighted the leading contribution of regional pain conditions (low back pain and neck pain in particular) to the global burden of disability. However, to date, there has not been a systematic approach to measuring the global burden of disease attributable to neuropathic pain (NP) conditions. This article gives a brief overview of the concept of burden of disease, the underlying drivers, and dynamics of disease burden at a population level and proposes an agenda in relation to NP for developing the conceptual and empirical evidence base necessary for estimating the global burden of NP.
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Nerve growth factor (NGF) injected into the human skin causes local hyperalgesia to mechanical and electrical stimuli lasting for weeks. Pig data suggested axonal sensitization of C-nociceptors as a contributing mechanism. Here, we recorded single C-nociceptors in 11 human subjects 3 weeks after intracutaneous injection of 1 μg NGF into the foot dorsum. ⋯ The sensitization included sensory and axonal components affecting both activation thresholds and supra-threshold responses. Our data suggest that a combination of sensory sensitization and axonal hyperexcitability is underlying the localized hyperalgesia by facilitating action potential generation and conduction. Axonal changes were also found in the asymptomatic skin surrounding the NGF-treatment sites, thereby possibly reflecting "nociceptive priming."