Pain
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We conducted a postal survey to assess the prevalence and characteristics of neuropathic pain and migraine in a cohort of multiple sclerosis (MS) patients. Of the 1300 questionnaires sent, 673 could be used for statistical analysis. Among the respondents, the overall pain prevalence in the previous month was 79%, with 51% experiencing pain with neuropathic characteristics (NCs) and 46% migraine. ⋯ Migraine, but not NC pain, was associated with age, disease duration, relapsing-remitting course, and interferon-beta treatment. This suggests that NC pain and migraine are mediated by different mechanisms. Therefore, pain mechanisms that specifically operate in MS patients need to be characterized to design optimal treatments for these individuals.
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Activation of glial cells and neuro-glial interactions are emerging as key mechanisms underlying chronic pain. Accumulating evidence has implicated 3 types of glial cells in the development and maintenance of chronic pain: microglia and astrocytes of the central nervous system (CNS), and satellite glial cells of the dorsal root and trigeminal ganglia. Painful syndromes are associated with different glial activation states: (1) glial reaction (ie, upregulation of glial markers such as IBA1 and glial fibrillary acidic protein (GFAP) and/or morphological changes, including hypertrophy, proliferation, and modifications of glial networks); (2) phosphorylation of mitogen-activated protein kinase signaling pathways; (3) upregulation of adenosine triphosphate and chemokine receptors and hemichannels and downregulation of glutamate transporters; and (4) synthesis and release of glial mediators (eg, cytokines, chemokines, growth factors, and proteases) to the extracellular space. ⋯ Glial activation also occurs in acute pain conditions, and acute opioid treatment activates peripheral glia to mask opioid analgesia. Thus, chronic pain could be a result of "gliopathy," that is, dysregulation of glial functions in the central and peripheral nervous system. In this review, we provide an update on recent advances and discuss remaining questions.
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The molecular/genetic era has seen the discovery of a staggering number of molecules implicated in pain mechanisms [18,35,61,69,96,133,150,202,224]. This has stimulated pharmaceutical and biotechnology companies to invest billions of dollars to develop drugs that enhance or inhibit the function of many these molecules. Unfortunately this effort has provided a remarkably small return on this investment. ⋯ To paraphrase a recent editorial in Science magazine [223], although we live in the Golden age of Genetics, the fundamental unit of biology is still arguably the cell, and the cell is the critical structural and functional setting in which the function of pain-related molecules must be understood. This review summarizes our current understanding of the nociceptor as a cell-biological unit that responds to a variety of extracellular inputs with a complex and highly organized interaction of signaling molecules. We also discuss the insights that this approach is providing into peripheral mechanisms of chronic pain and sex dependence in pain.
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In order to understand how nociceptive information is processed in the spinal dorsal horn we need to unravel the complex synaptic circuits involving interneurons, which constitute the vast majority of the neurons in laminae I-III. The main limitation has been the difficulty in defining functional populations among these cells. We have recently identified 4 non-overlapping classes of inhibitory interneuron, defined by expression of galanin, neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS) and parvalbumin, in the rat spinal cord. ⋯ Parvalbumin cells did not express either activity-dependent marker following any of these stimuli. These results suggest that interneurons belonging to the NPY, nNOS and galanin populations are involved in attenuating pain, and for NPY and nNOS cells this is likely to result from direct inhibition of nociceptive projection neurons. They also suggest that the nociceptive inputs to the nNOS cells differ from those to the galanin and NPY populations.
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Pain experiences, learning, and genetic factors have been proposed to shape attentional and emotional processes related to pain. We aimed at investigating whether a singular major pain experience also changes cognitive-emotional processing. The influence of acute postoperative pain after cosmetic surgery of the thorax was tested in 80 preoperatively pain-free male individuals. ⋯ In contrast, the attentional biases in the dot-probe task could not be predicted by the pain ratings. The levels of pain catastrophizing and pain hypervigilance increased in the acute phase after surgery when influenced by acute pain and declined, along with pain anxiety, during the next 3 months. In conclusion, a one-time intense pain experience, such as acute postoperative pain, appeared to produce at least short-lived changes in the attentional and emotional processing of pain.