2023 Fiscal Year Final Research Report

Elucidation of abnormal functioning of neuronal circuits underlying neuropathic pain and its application for drug discovery

Research Project

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Project/Area Number	19H05658
Research Category	Grant-in-Aid for Scientific Research (S)
Allocation Type	Single-year Grants
Review Section	Broad Section I
Research Institution	Kyushu University
Principal Investigator	Tsuda Makoto 九州大学, 薬学研究院, 教授 (40373394)
Co-Investigator(Kenkyū-buntansha)	八坂敏一新潟医療福祉大学, リハビリテーション学部, 教授 (20568365) 山下智大九州大学, 薬学研究院, 講師 (30645635)
Project Period (FY)	2019-06-26 – 2024-03-31
Keywords	神経障害性アロディニア / 一次求心性神経Aβ線維 / 光遺伝学 / 脊髄後角神経回路
Outline of Final Research Achievements	Combining our newly established method for evaluating neuropathic allodynia by selective stimulation of primary afferent Aβ fibers (touch-sensing fibers) with a method for regulating cell subset-specific functions using viral vectors, we identified several neuronal and glial subsets important for neuropathic allodynia. In particular, dysfunction of the NPY+ neuronal subset after nerve injury was found to play a central role in the development of neuropathic allodynia. In addition, we found that signaling from glial cells is responsible for the dysfunction of NPY+ neurons. Furthermore, we also showed that an analgesic effect of the clinically approved drug duloxetine requires the activation of NPY+ neurons, and we identified compounds that can enhance the function of NPY+ neurons.
Free Research Field	神経薬理学
Academic Significance and Societal Importance of the Research Achievements	神経障害性アロディニアの発症メカニズムの中核を担うNPY+神経等の神経やグリア細胞サブセットを同定したことは、感覚情報伝達系の制御機構および触覚信号の痛覚信号への誤変換の仕組みを紐解く重要な成果であり、神経障害性疼痛の発症機序の解明への大きな前進となった。さらに本研究では、神経障害性アロディニアに直結するNPY+神経サブセットの機能低下を正常化する新たな方法やそれを実現しうる化合物も見出した。以上より、本研究で同定したNPY+神経や化合物等が今後の鎮痛薬開発における新たな標的やシーズとなる可能性が期待される。