Articles: neuropathic-pain.
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Best Pract Res Clin Rheumatol · Feb 2015
ReviewUpdate on the genetics of the fibromyalgia syndrome.
Fibromyalgia syndrome (FMS), a condition characterized by chronic widespread pain and tenderness, is a complex condition considered to represent a paradigm of centralized pain. FMS has demonstrated a clear familial aggregation, and hence it is considered to have a genetic background. ⋯ In addition, genome-wide sequencing scanning (genome-wide association study (GWAS)) is increasingly being harnessed for the study of chronic pain, including FMS. Micro RNAs are another novel field of research related to posttranscriptional inhibition of gene expression, which are currently regarding the pathogenesis of FMS.
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Neuropathic pain is an important public health problem for which only a few treatments are available. Preclinical studies show that melatonin (MLT), a neurohormone acting on MT1 and MT2 receptors, has analgesic properties, likely through MT2 receptors. Here, we determined the effects of the novel selective MLT MT2 receptor partial agonist N-{2-([3-bromophenyl]-4-fluorophenylamino)ethyl}acetamide (UCM924) in 2 neuropathic pain models in rats and examined its supraspinal mechanism of action. ⋯ Using double staining immunohistochemistry, we found that MT2 receptors are expressed by glutamatergic neurons in the rostral ventrolateral periaqueductal gray. Using in vivo electrophysiology combined with tail flick, we observed that microinjection of UCM924 into the ventrolateral periaqueductal gray decreased tail flick responses, depressed the firing activity of ON cells, and activated the firing of OFF cells; all effects were MT2 receptor-dependent. Altogether, these data demonstrate that selective MT2 receptor partial agonists have analgesic properties through modulation of brainstem descending antinociceptive pathways, and MT2 receptors may represent a novel target in the treatment of neuropathic pain.
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Anasthesiol Intensivmed Notfallmed Schmerzther · Feb 2015
Review[Perioperative management of patients with opioid tolerance and misuse].
Patients with opioid pretreatment can be divided into different groups. While patients after successful drug addiction treatment with or without drug replacement therapy usually not require an extensive perioperative pain therapy, patients with persistent chronic pain and patients with an existing opioid addiction regularly are challenging for the anesthetist. Important pathophysiological issues among the patients include opioid tolerance, opioid-induced hyperalgesia (OIH) as well as acute withdrawal symptomes. ⋯ A similar statement applies to clonidine and dexmedetomidine, which probably induce analgesia by activation of the descending antinociceptive noradrenergic system. The intraoperative administration of S-ketamine is recommended for patients who either already have developed opioid tolerance or suffer from neuropathic pain, and by which postoperative pain is high and was already shown to be poorly adjusted. Other therapeutic options such as intraoperative administration of magnesium or lidocaine may be promising approaches.
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Brain Behav. Immun. · Feb 2015
Calpain-2 contributes to neuropathic pain following motor nerve injury via up-regulating interleukin-6 in DRG neurons.
Motor nerve injury by L5 ventral root transection (L5-VRT) initiates interleukin-6 (IL-6) up-regulation in primary afferent system contributing to neuropathic pain. However, the early upstream regulatory mechanisms of IL-6 after L5-VRT are still unknown. Here, we monitored both the activity of calpain, a calcium-dependent protease suggested as one of the earliest mediators for cytokine regulation, and the expression of IL-6 in bilateral L4-L6 dorsal root ganglias (DRGs) soon after L5-VRT. ⋯ Inhibition of calpain by pre-treatment with MDL28170 (25mg/kg, i.p.) attenuated the rat mechanical allodynia and prevented the early up-regulation of IL-6 following L5-VRT. Addition of exogenous calpain-2 onto the surface of left L5 DRG triggered a temporal allodynia and increased IL-6 in bilateral DRGs simultaneously. Taken together, the early increase of calpain-2 in L5-VRT rats might be responsible for the induction of allodynia via up-regulating IL-6 in DRG neurons.
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Neuropathic pain is a debilitating condition caused by damage to the somatosensory nervous system, such as peripheral nerve injury. The immune system, and in particular the adaptive T cell response, plays a key role in mediating such pain. Regulatory T (Treg) cells are a small subpopulation of inhibitory T cells that prevent autoimmunity, limit immunopathology and maintain immune homeostasis. ⋯ In particular, we observed significant increases in systemic concentration of RANTES, IL-2 and IL-5, and significant decreases in IL-12 and IFN-γ in nerve-injured Treg-depleted DEREG mice. Further analysis indicated a substantial increase in the serum concentration of IL-12p40 as a direct result of Treg cell depletion. These results suggest that depletion of Foxp3+ Treg cells promote nerve injury-induced pain hypersensitivity, partially by inducing altered systemic concentrations of cytokines, which may act to regulate neuropathic pain.