• Neuroscience research · Feb 2014

    Involvement of Wnt/β-catenin signaling in the development of neuropathic pain.

    • Takahide Itokazu, Yasufumi Hayano, Ryosuke Takahashi, and Toshihide Yamashita.
    • Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Neurology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
    • Neurosci. Res. 2014 Feb 1;79:34-40.

    AbstractDespite tremendous research effort in the field, our current understanding of the molecular mechanisms underlying neuropathic pain is still incomplete. In the present study, our objective was to elucidate the involvement of the Wnt/β-catenin signaling pathway in the development of neuropathic pain. We showed that Wnt/β-catenin signaling is activated in the spinal cord dorsal horn after partial sciatic nerve ligation (PSL). Expression of Wnt3a, a prototypic Wnt ligand that activates the Wnt/β-catenin pathway, was also upregulated in the dorsal horn. We then tested the effect of intrathecal administration of XAV939, a Wnt/β-catenin signaling inhibitor, and found that this treatment effectively attenuated the induction of neuropathic pain. Conversely, intrathecal administration of Wnt3a to the lumbar spinal cord of naïve animals triggered the development of allodynia. These results suggest a critical involvement of the Wnt/β-catenin pathway in the development of neuropathic pain. Moreover, we also found that PSL-induced microglial activation was significantly suppressed by intrathecal administration of XAV939 treatment. Because it was revealed that Wnt3a treatment triggered brain-derived neurotrophic factor (BDNF) release from microglial cells in vitro, it is possible that Wnt3a upregulation in the dorsal horn leads to the activation of microglial cells, then triggers BDNF secretion that is responsible for the establishment of neuropathic pain. Further studies will be needed for the comprehensive understanding of the roles of Wnt/β-catenin signaling in the development of neuropathic pain.Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

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