Wnt/beta-Catenin Signaling Contributes to Vincristine-Induced Neuropathic Pain

Physiol Res. 2020 Aug 31;69(4):701-710. doi: 10.33549/physiolres.934314. Epub 2020 Jun 25.


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 terms

  • Animals
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neuralgia / chemically induced
  • Neuralgia / metabolism
  • Neuralgia / pathology*
  • Signal Transduction
  • Vincristine / adverse effects*
  • Vincristine / pharmacology
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism*


  • Antineoplastic Agents, Phytogenic
  • CTNNB1 protein, mouse
  • Wnt Proteins
  • beta Catenin
  • Vincristine