Open AccessWnt/β-catenin signaling contributes to vincristine-induced neuropathic pain
Author(s) -
Chen Hu,
Yanyan Zhao,
Cui Yb,
Zhang Hh,
Huang Gl,
Liu Y,
Liu Yf
Publication year - 2020
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.934314
Subject(s) - wnt signaling pathway , neuropathic pain , mapk/erk pathway , microglia , signal transduction , cancer research , beta catenin , medicine , pharmacology , microbiology and biotechnology , endocrinology , inflammation , biology
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/β-catenin signaling, which led to the activation of astrocytes, microglia, the release of inflammatory cytokines tumour necrosis factor (TNF)-α, 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/β-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-α, MCP-1 and MAPK/ERK signaling in the spinal cord, which was triggered by VCR-induced Wnt/β-catenin signaling upregulation. These results suggest that Wnt/β-catenin signaling plays a critical role in VCR-induced neuropathic pain and provides evidence for potential interfering with Wnt/β-catenin signaling to ameliorate VCR-induced neuropathic pain.