Articles: neuropathic-pain.
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Brain Behav. Immun. · Mar 2014
Up-regulation of interleukin-23 induces persistent allodynia via CX3CL1 and interleukin-18 signaling in the rat spinal cord after tetanic sciatic stimulation.
Tetanic stimulation of the sciatic nerve (TSS) induces sciatic nerve injury and long-lasting pain hypersensitivity in rats, and spinal glial activation and proinflammatory cytokines releases are involved. In the present study, we showed that spinal interleukin (IL)-23 and its receptor, IL-23R, are crucial for the development of mechanical allodynia after TSS. In the spinal dorsal horn, both IL-23 and IL-23R are expressed in astrocytes, and this expression is substantially increased after TSS. ⋯ Activation of CX3CR1 and IL-18R induced similar behavioral and biochemical changes to those observed after TSS. These results indicate that the interaction among CX3CL1, IL-18 and IL-23 signaling in the spinal cord plays a critical role in the development of allodynia. Thus, interrupting this chemokine-cytokine network might provide a novel therapeutic strategy for neuropathic pain.
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Anesthesia and analgesia · Mar 2014
The endocannabinoid anandamide inhibits voltage-gated sodium channels nav1.2, nav1.6, nav1.7, and nav1.8 in Xenopus oocytes.
Anandamide is an endocannabinoid that regulates multiple physiological functions by pharmacological actions, in a manner similar to marijuana. Recently, much attention has been paid to the analgesic effect of endocannabinoids in terms of identifying new pharmacotherapies for refractory pain management, but the mechanisms of the analgesic effects of anandamide are still obscure. Voltage-gated sodium channels are believed to play important roles in inflammatory and neuropathic pain. We investigated the effects of anandamide on 4 neuronal sodium channel α subunits, Nav1.2, Nav1.6, Nav1.7, and Nav1.8, to explore the mechanisms underlying the antinociceptive effects of anandamide. ⋯ Anandamide inhibited the function of α subunits in neuronal sodium channels Nav1.2, Nav1.6, Nav1.7, and Nav1.8. These results help clarify the mechanisms of the analgesic effects of anandamide.
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Reg Anesth Pain Med · Mar 2014
Ghrelin Alleviates Neuropathic Pain Through GHSR-1a-Mediated Suppression of the p38 MAPK/NF-κB Pathway in a Rat Chronic Constriction Injury Model.
Neuropathic pain is related to the sustained activation of neuroglial cells and the production of proinflammatory cytokines in the spinal dorsal horn. Ghrelin, the endogenous ligand for growth hormone secretagogue receptor 1a (GHSR-1a), has been shown to inhibit the activation of microglia and the release of proinflammatory cytokines. The purpose of this study was to investigate the role of ghrelin/GHSR-1a signaling in neuropathic pain and to understand the associated mechanisms. ⋯ Our present study demonstrated that ghrelin alleviated neuropathic pain through a GHSR-1a-mediated suppression of the p38 MAPK/NF-κB pathway.
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This manuscript reviews peer-reviewed literature published from 2010-2012 relevant to the management of chronic pain in the primary care setting. ⋯ There is growing evidence for the risks, benefits, and limitations of the multiple modalities available to primary care providers for the management of chronic pain. The dissemination and implementation of the evidence from these studies as well as novel system-level interventions warrant additional study and support from clinicians, educators, and policy makers.