Elucidation of spinal mechanism of chronic myalgia using novel in vivo patch clamp method and search for therapeutic agents.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K09323
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: University of Toyama
• Principal Investigator: Uta Daiuek 富山大学, 学術研究部薬学・和漢系, 准教授 (70598416)
• Co-Investigator(Kenkyū-buntansha): 田口 徹 新潟医療福祉大学, リハビリテーション学部, 教授 (90464156)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 線維筋痛症 / 電気生理学 / 痛み / 脊髄後角 / in vivoパッチクランプ

Outline of Final Research Achievements

We examined the activities of superficial dorsal horn (SDH) neurons, as well as excitatory and inhibitory postsynaptic inputs to SDH neurons, using a putative rat model of fibromyalgia that was established by injecting reserpine. Extracellular recordings in vivo revealed that SDH neurons were sensitized to mechanical stimulation applied to the neurons' receptive fields, and the mechanically sensitized neurons were spontaneously more active. Using patch-clamp recordings in vivo, spontaneous excitatory synaptic responses to SDH neurons were found to increase in the pain model. These results demonstrate that the SDH neurons were strongly sensitized in response to the reserpine treatment, and that increased excitatory postsynaptic inputs could be responsible for the spinal nociceptive hypersensitivity in the putative FM model.

Free Research Field

疼痛学、掻痒学、神経薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究により、これまで国内外で全く行われていなかった筋痛時における脊髄後角での神経機構の変容の一端を解明することが出来た。また本研究で用いた技術は世界初のものであり、今後の生理学的意義も非常に大きい。また、得られた成果をもとに、今後筋痛覚過敏に対する治療薬開発のための分子ターゲットの発見に期待が持てるとともに、まだ不明点の多い線維筋痛症の病態メカニズム解明に貢献できるものと思われる。