Pain
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The current International Association for the Study of Pain (IASP) definition of pain as "An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" was recommended by the Subcommittee on Taxonomy and adopted by the IASP Council in 1979. This definition has become accepted widely by health care professionals and researchers in the pain field and adopted by several professional, governmental, and nongovernmental organizations, including the World Health Organization. In recent years, some in the field have reasoned that advances in our understanding of pain warrant a reevaluation of the definition and have proposed modifications. ⋯ This review provides a synopsis of the critical concepts, the analysis of comments from the IASP membership and public, and the committee's final recommendations for revisions to the definition and notes, which were discussed over a 2-year period. The task force ultimately recommended that the definition of pain be revised to "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage," and that the accompanying notes be updated to a bulleted list that included the etymology. The revised definition and notes were unanimously accepted by the IASP Council early this year.
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One of the potential mechanisms of motor cortex stimulation by noninvasive brain stimulation (NIBS) effects on pain is through the restoration of the defective endogenous inhibitory pain pathways. However, there are still limited data on quantitative sensory testing (QST), including conditioned pain modulation (CPM), supporting this mechanism. This systematic review and meta-analysis aimed to evaluate the effects of noninvasive motor cortex stimulation on pain perception as indexed by changes in QST outcomes. ⋯ Thirty-eight studies were included (1178 participants). We found significant increases of pain threshold in healthy subjects (ES = 0.16, 95% CI = 0.02-0.31, I2 = 22.2%) and pain populations (ES = 0.48, 95% CI = 0.15-0.80, I2 = 68.8%), and homogeneous higher CPM effect (pain ratings reduction) in healthy subjects (ES = -0.39, 95% CI = -0.64 to -0.14, I2 = 17%) and pain populations (ES = -0.35, 95% CI = -0.60 to -0.11, I2 = 0%) in the active NIBS group compared with sham. These results support the idea of top-down modulation of endogenous pain pathways by motor cortex stimulation as one of the main mechanisms of pain reduction assessed by QST, which could be a useful predictive and prognostic biomarker for chronic pain personalized treatment with NIBS.
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Pharmacological tools for chronic visceral pain management are still limited and inadequate. A3 adenosine receptor (A3AR) agonists are effective in different models of persistent pain. Recently, their activity has been related to the block of N-type voltage-gated Ca2+ channels (Cav2.2) in dorsal root ganglia (DRG) neurons. ⋯ Furthermore, patch-clamp recordings showed that A3AR agonists inhibited Cav2.2 in dorsal root ganglia neurons isolated from either control or DNBS-treated rats. The effect on Ca2+ current was PD173212-sensitive and prevented by MRS1523. A3AR agonists are effective in relieving visceral hypersensitivity induced by DNBS, suggesting a potential therapeutic role against abdominal pain.
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Neuropathy is a common complication of long-term diabetes that impairs quality of life by producing pain, sensory loss and limb amputation. The presence of neuropathy in both insulin-deficient (type 1) and insulin resistant (type 2) diabetes along with the slowing of progression of neuropathy by improved glycemic control in type 1 diabetes has caused the majority of preclinical and clinical investigations to focus on hyperglycemia as the initiating pathogenic lesion. ⋯ For example, peripheral nerve contains insulin receptors that transduce the neurotrophic and neurosupportive properties of insulin, independent of systemic glucose regulation, while the detection of neuropathy and neuropathic pain in patients with metabolic syndrome and failure of improved glycemic control to protect against neuropathy in cohorts of type 2 diabetic patients has placed a focus on the pathogenic role of dyslipidemia. This review provides an overview of current understanding of potential initiating lesions for diabetic neuropathy and the multiple downstream mechanisms identified in cell and animal models of diabetes that may contribute to the pathogenesis of diabetic neuropathy and neuropathic pain.
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Withdrawal from systemic opioids can induce long-term potentiation (LTP) at spinal C-fibre synapses ("opioid-withdrawal-LTP"). This is considered to be a cellular mechanism underlying opioid withdrawal-induced hyperalgesia, which is a major symptom of the opioid withdrawal syndrome. Opioids can activate glial cells leading to the release of proinflammatory mediators. ⋯ In striking contrast, in female rats, the induction of morphine-withdrawal-LTP was independent of spinal glial cells. Instead, blocking µ-opioid receptors in the spinal cord was sufficient to prevent a facilitation of synaptic strength. Our study revealed fundamental sex differences in the mechanisms underlying morphine-withdrawal-LTP at C-fibre synapses: supraspinal and gliogenic mechanisms in males and a spinal, glial cell-independent mechanism in females.