Effects Of Ghrelin On Pgsk-3 Beta And Beta-Catenin Expression When Protects Against Neuropathic Pain Behavior In Rats Challenged With Chronic Constriction Injury
SCIENTIFIC REPORTS(2019)
摘要
Ghrelin has been shown to alleviate neuropathic pain by inhibiting the release of proinflammatory cytokines. The purpose of this study was to investigate the role of GSK-3 beta/beta-catenin signaling in mediating the effect of ghrelin on neuropathic pain and to understand the associated mechanisms. Chronic constriction injury (CCI) of the sciatic nerve was used to establish a rat model of neuropathic pain. Hyperalgesia and allodynia were evaluated by observing the mechanical withdrawal threshold and the thermal withdrawal latency. Wnt3a and beta-catenin protein expression and GSK-3 beta phosphorylation were detected by western blotting analysis. The levels of tumor necrosis factor-alpha and IL-1 beta were determined using an enzyme-linked immunosorbent assay. In addition, we used immunohistochemical analysis to determine the levels of GSK-3 beta phosphorylation in the dorsal horn of the spinal cord. Intrathecal delivery of ghrelin effectively ameliorated CCI-induced mechanical allodynia and thermal hyperalgesia at 7 and 14 days and reduced the levels of tumor necrosis factor-alpha. Ghrelin inhibited CCI-induced GSK-3 beta activation and beta-catenin overexpression in the spinal dorsal horn. Moreover, intrathecal injection of ghrelin suppressed the activation of GSK-3 beta in the spinal dorsal horn of CCI rats, as assessed by immunohistochemical analysis. Our data indicated that ghrelin could markedly alleviate neuropathic pain by inhibiting the expression of beta-catenin, via the suppression of GSK-3 beta activation, in the spinal cord of CCI rats.
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关键词
Neuropathic pain,Quality of life,Science,Humanities and Social Sciences,multidisciplinary
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