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演題詳細

Poster

痛覚、痒み、及びその障害
Pain, Itch and Their Disorders

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

神経因性疼痛の発症にWnt/β-カテニン経路が関与する
Involvement of Wnt/β-catenin signaling in the development of neuropathic pain

  • P3-170
  • 糸数 隆秀 / Takahide Itokazu:1,2,3 早野 泰史 / Yasufumi Hayano:2 高橋 良輔 / Ryosuke Takahashi:3 山下 俊英 / Toshihide Yamashita:2 
  • 1:南京都病院 / Minami-kyoto National Hospital 2:大阪大学医学系研究科 分子神経科学 / Dept Mol Neurosci, Osaka Univ, Osaka, Japan 3:京都大学大学院医学研究科 臨床神経学 / Dept Neurol, Kyoto Univ, Kyoto, Japan 

Clinical management of neuropathic pain is currently aimed at achieving relief from symptoms of this condition; unfortunately, in many cases such efforts fall short of this goal. Despite the tremendous efforts, our understanding about molecular mechanism underlying neuropathic pain is still incomplete. In the present study, we intended to elucidate the involvement of Wnt/β-catenin pathway signaling in the development of neuropathic pain. Firstly, we revealed that Wnt/β-catenin signaling is activated in the spinal cord dorsal horn after partial sciatic nerve ligation (PSL). We also showed that Wnt3a, a prototypic Wnt ligand which activates Wnt/β-catenin pathway, was upregulated in the dorsal horn. Therefore, we tested the effect of intrathecal administration of XAV939 (Wnt/β-catenin signaling inhibitor), and found that such treatment effectively attenuates the induction of neuropathic pain. On the other hand, intrathecal administration of recombinant Wnt3a to the lumber spinal cord of naive animals triggered the development of allodynia. These results suggest critical involvement of Wnt/β-catenin pathway in the development of neuropathic pain. Interestingly, immunohistochemical analysis revealed that XAV939 treatment partially but significantly suppressed the activation of microglia in the dorsal horn after PSL. Because a growing body of evidence indicates that interactions between neurons and microglia are critical in establishing neuropathic pain, it is possible that the beneficial effect of the Wnt/β-catenin inhibitor is through suppressing pathologic activation of microglia induced by peripheral nerve injury.

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