2022 Fiscal Year Final Research Report

Mechanisms of exercise-induced hypoalgesia

Research Project

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Project/Area Number	18K10719
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 59010:Rehabilitation science-related
Research Institution	Wakayama Medical University (2018-2019, 2021-2022) Takarazuka University of Medical and Health Care (2020)
Principal Investigator	Kami Katsuya 和歌山県立医科大学, 医学部, 特別研究員 (20204612)
Co-Investigator(Kenkyū-buntansha)	仙波恵美子和歌山県立医科大学, 医学部, 名誉教授 (00135691) 田島文博和歌山県立医科大学, 医学部, 教授 (00227076)
Project Period (FY)	2018-04-01 – 2023-03-31
Keywords	運動による疼痛抑制 / 自発運動 / 坐骨神経部分損傷 / 免疫組織化学染色 / 機械的アロディニア / 熱痛覚過敏 / 扁桃体 / 腹側海馬
Outline of Final Research Achievements	It is known that exercise produces analgesic effects (exercise-induced hypoalgesia (EIH)) in animal models and chronic pain patients. Using neuropathic pain (NPP) model mice, we found that voluntary exercise (VE) activated glutamate (Glu) neurons in the medial basal Amyg projecting to the nucleus accumbens (NAc), while it almost completely suppressed NPP-induced activation of GABA neurons in the central nucleus of the Amyg (CeA). VE in NPP model mice inhibits GABA interneurons in the PL and IL of the mPFC, probably via inhibition of the BLA–mPFC pathway, which disinhibits Glu neurons working in the mPFC–NAc pathway, thereby activating NAc GABA neurons. In addition, VE in NPP model mice induced significant activation of GABA neurons in the NAc. The findings suggest that activation of GABA neurons in the NAc may inhibit GABA interneurons located in the latVTA, which results in disinhibition of VTA DA neurons and, therefore, upregulation of DA release into the NAc.
Free Research Field	疼痛
Academic Significance and Societal Importance of the Research Achievements	運動による疼痛抑制効果(Exercise-induced hypoalgesia：EIH)の発現には、脳報酬系の活性化(VTA-DA)が重要な役割を担うことが知られている。しかし運動がVTA-DAニューロンを活性化する神経経路は不明であり、これらに取り組むことはEIHを生み出すメカニズムのさらなる解明に繋がる（学術的意義）。本研究の遂行により得られた成果は、慢性痛患者に運動療法を推奨する科学的根拠とEIH効果を生み出す効果的な運動プログラムを確立するための基礎データを提供することができ、慢性痛患者のQuality of Life の向上に貢献することが期待される（社会的意義）。