Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the mechanisms underlying CNP remain elusive. In the present study, CNP was induced by repeated intraperitoneal injection of vincristine (VCR) into male C57BL/6J mice. VCR administration caused significant activation of Wnt/beta-catenin signaling, which led to the activation of astrocytes, microglia, the release of inflammatory cytokines tumour necrosis factor (TNF)-alpha, monocyte chemoattractant protein-1 (MCP-1) and the activation of subsequent mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling pathway in CNP mice. Blocking Wnt/beta-catenin signaling by intrathecal administration of the inhibitors of Wnt response (IWR) effectively attenuated VCR-induced neuropathic pain. Furthermore, IWR inhibited the activation of astrocytes, microglia, TNF-alpha, MCP-1 and MAPK/ERK signaling in the spinal cord, which was triggered by VCR-induced Wnt/beta-catenin signaling upregulation. These results suggest that Wnt/beta-catenin signaling plays a critical role in VCR-induced neuropathic pain and provides evidence for potential interfering with Wnt/beta-catenin signaling to ameliorate VCR-induced neuropathic pain.

• MeSH
• antitumorózní látky fytogenní škodlivé účinky   farmakologie   MeSH
• beta-katenin metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádory farmakoterapie   metabolismus   patologie   MeSH
• neuralgie chemicky indukované   metabolismus   patologie   MeSH
• proteiny Wnt metabolismus   MeSH
• signální dráha Wnt * MeSH
• signální transdukce MeSH
• vinkristin škodlivé účinky   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH