神経障害性疼痛における免疫系細胞に発現するtransient receptor potential melastatin 2チャネルの役割

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  • 中川 貴之
    京都大学大学院薬学研究科生体機能解析学分野
  • 勇 昂一
    京都大学大学院薬学研究科生体機能解析学分野
  • 原口 佳代
    京都大学大学院薬学研究科生体機能解析学分野
  • 宗 可奈子
    京都大学大学院薬学研究科生体機能解析学分野
  • 朝倉 佳代子
    京都大学大学院薬学研究科生体機能解析学分野
  • 白川 久志
    京都大学大学院薬学研究科生体機能解析学分野
  • 金子 周司
    京都大学大学院薬学研究科生体機能解析学分野

書誌事項

タイトル別名
  • Roles of Transient Receptor Potential Melastatin 2 Expressed on Immune Cells in Neuropathic Pain
  • Symposium Review 神経障害性疼痛における免疫系細胞に発現するtransient receptor potential melastatin 2チャネルの役割
  • Symposium Review シンケイ ショウガイセイ トウツウ ニ オケル メンエキケイ サイボウ ニ ハツゲン スル transient receptor potential melastatin 2 チャネル ノ ヤクワリ

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抄録

  Neuropathic pain is a pathological pain condition that often results from peripheral nerve injury. Several lines of evidence suggest that neuroinflammation mediated by the interaction between immune cells and neurons plays an important role in the pathogenesis of neuropathic pain. Transient receptor potential melastatin 2 (TRPM2) is a nonselective Ca2+-permeable cation channel that acts as a sensor for reactive oxygen species. Recent evidence suggests that TRPM2 expressed on immune cells plays an important role in immune and inflammatory responses. In this study, we examined the roles of TRPM2 expressed on immune and glial cells in neuropathic pain. TRPM2 deficiency attenuated pain behaviors (mechanical allodynia, thermal hyperalgesia and spontaneous pain behaviors) in various kinds of inflammatory and neuropathic pain, but not in nociceptive pain models. In peripheral nerve injury-induced neuropathic pain models, TRPM2 deficiency diminished infiltration of neutrophils mediated through CXCL2 production from macrophages around the injured peripheral nerve and activation of spinal microglia, suggesting that TRPM2 expressed on macrophages and microglia aggravates peripheral and spinal pronociceptive inflammatory responses. Furthermore, we examined the infiltration of peripheral immune cells into the injured nerve and spinal cord using bone marrow chimeric mice by crossing wildtype and TRPM2-knockout mice. The results suggest that TRPM2 plays an important role in the infiltration of peripheral immune cells, particularly macrophages, into the spinal cord, rather than into the injured nerves. The spinal infiltration of macrophages mediated by TRPM2 may contribute to the pathogenesis of neuropathic pain.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 134 (3), 379-386, 2014-03-01

    公益社団法人 日本薬学会

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