Elucidation of the mechanisms underlying muscle adaptation to exercise via neuromuscular crosstalk based on biomedical engineering analysis.

• Project/Area Number: 18H03525
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Chubu University
• Principal Investigator: Katanosaka Kimiaki 中部大学, 生命健康科学部, 准教授 (50335006)
• Co-Investigator(Kenkyū-buntansha): 金川 基 愛媛大学, 医学系研究科, 教授 (00448044) ; 永森 收志 東京慈恵会医科大学, 医学部, 准教授 (90467572) ; 片野坂 友紀 岡山大学, 医歯薬学総合研究科, 助教 (60432639)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 骨格筋 / 運動適応 / 筋痛 / 侵害受容 / 機械受容 / メカノセンサー / 感覚神経 / 血管 / 膜修復 / 適応

Outline of Final Research Achievements

The objective of this study was to clarify the contribution of a mechanoreceptor molecule in primary sensory neuron and muscle to delayed onset muscle soreness in skeletal muscle after exercise and its adaptation process, and to identify the molecules involved in muscle adaptation to exercise by multi-omics data analysis. We found that the expression of proteins involved in the membrane fusion process was increased in the post-exercise muscle and was unchanged in muscle after adaptation. The contribution of the mechanoreceptor TRPV2 to muscle soreness appeared to be small. The results suggest that enhanced membrane repair may be involved in muscle adaptation to exercise and relief from muscular pain.

Academic Significance and Societal Importance of the Research Achievements

運動後に感覚神経を介して痛みを生じ、しばらくして回復をみせる遅発性筋痛において、神経と筋で働く重要分子を探索し、反復的な運動に適応して筋痛を低下させる可能性のある分子を同定した。これらの分子の機能を亢進させ、骨格筋自身の適応機構を賦活化する方法を見出すことにより、筋性疼痛の緩和、運動器障害の予防、運動療法の効率化等につながる新たな治療戦略としての応用が期待できる。

Research Products

• [Journal Article] Insulin potentiates the response to capsaicin in dorsal root ganglion neurons in vitro and muscle afferents ex vivo in normal healthy rodents. (2022)
  • Author(s): Hori Amane, Hotta Norio, Fukazawa Ayumi, Estrada Juan A., Katanosaka Kimiaki, Mizumura Kazue, Sato Jun, Ishizawa Rie, Kim Han‐Kyul, Iwamoto Gary A., Vongpatanasin Wanpen, Mitchell Jere H., Smith Scott A., Mizuno Masaki
  • Journal Title: The Journal of Physiology Volume: 600 Issue: 3 Pages: 531-545
  • DOI: 10.1113/jp282740
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Insulin potentiates the response to mechanical stimuli in small dorsal root ganglion neurons and thin fibre muscle afferents in vitro. (2019)
  • Author(s): Hotta N, Katanosaka K, Mizumura K, Iwamoto GA, Ishizawa R, Kim HK, Vongpatanasin W, Mitchell JH, Smith SA, Mizuno M.
  • Journal Title: J Physiol. Volume: 597 Issue: 20 Pages: 5049-5062
  • DOI: 10.1113/jp278527
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Corneal Sensory Experience via Transient Receptor Potential Vanilloid 1 Accelerates the Maturation of Neonatal Tearing (2019)
  • Author(s): Jin Kai、Imada Toshihiro、Nakamura Shigeru、Izuta Yusuke、Oonishi Erina、Shibuya Michiko、Sakaguchi Hisayo、Tanabe Hirotaka、Ito Masataka、Katanosaka Kimiaki、Tsubota Kazuo
  • Journal Title: The American Journal of Pathology Volume: 189 Issue: 9 Pages: 1699-1710
  • DOI: 10.1016/j.ajpath.2019.05.015
  • Peer Reviewed / Open Access
• [Journal Article] TRPV2 is required for mechanical nociception and the stretch-evoked response of primary sensory neurons. (2018)
  • Author(s): Kimiaki Katanosaka, Satomi Takatsu, Kazue Mizumura, Keiji Naruse, Yuki Katanosaka
  • Journal Title: Scientific Reports Volume: 8(1) Issue: 1 Pages: 16782-16791
  • DOI: 10.1038/s41598-018-35049-4
  • Peer Reviewed / Open Access
• [Presentation] Contribution of peripheral adenosine receptor to analgesia by intramuscular injection of drugs. (2022)
  • Author(s): Nasu T., Hibino Y., Katanosaka K., Mizumura K.
  • Organizer: 第99回日本生理学会大会
• [Presentation] 痛みのメカノバイオロジー (2022)
  • Author(s): 片野坂公明
  • Organizer: 第26回日本体力医学会東海地方会学術集会
  • Invited
• [Presentation] Involvement of transient receptor potential vanilloid 2（TRPV2）in mechanical nociception of adult mice. (2021)
  • Author(s): Kimiaki Katanosaka, Toru Taguchi, Satomi Takatsu, Kazue Mizumura, Keiji Naruse, Yuki Katanosaka.
  • Organizer: The 4th International TRP Meeting (TRP2021, Hybrid edition)
  • Int'l Joint Research
• [Presentation] TRPA1 contributes to lengthening contraction-induced muscular mechanical hyperalgesia. (2021)
  • Author(s): Hiroki Ota, Leo Washizawa, Koei Hayashi, Yuki Katanosaka, Kimiaki Katanosaka, Makiko Kashio, Makoto Tominaga, Toru Taguchi, Kazue Mizumura.
  • Organizer: The 4th International TRP Meeting (TRP2022, Hybrid edition)
  • Int'l Joint Research
• [Presentation] Analysis of Molecular Mechanisms Involved in Mechanical Adaptation: In the Case of Repeated Bout Effect on the Exercise-induced Muscle Pain. (2021)
  • Author(s): Hibino Y., Katanosaka Y., Katanosaka K.
  • Organizer: The 3rd International Yangtze River Delta Symposium on Mechanobiology and 9th Chinese National Symposium of Medical Biophysics.
  • Int'l Joint Research
• [Presentation] Repeated cold stress augments cardiovascular responses to triceps surae stretch in rats. (2021)
  • Author(s): 堀天，那須輝顕，片野坂公明，水村和枝，Masaki Mizuno，堀田典生
  • Organizer: 第76回日本体力医学会大会
• [Presentation] 細径線維受容器終末のTRPV2チャネルを介した機械痛覚の末梢神経機構 (2021)
  • Author(s): 田口 徹, 片野坂友紀, 太田大樹, 片野坂公明
  • Organizer: 第26回日本基礎理学療法学会
• [Presentation] 遅発性筋痛モデルラットの筋における機械受容チャネル Tmem120Aの発現増大 (2021)
  • Author(s): 太田大樹，大井理史，片野坂公明，田口 徹
  • Organizer: 第7回日本筋学会学術大会
• [Presentation] Decreased mechanical response of cutaneous nociceptors in TRPV2-deficient mice. (2020)
  • Author(s): 田口徹, 片野坂友紀, 片野坂公明
  • Organizer: 第43回日本神経科学大会
• [Presentation] Insulin potentiates capsaicin sensitivity at axon terminals and dorsal root ganglion neurons of thin fiber muscle afferents (2020)
  • Author(s): 堀天, 堀田典生, 片野坂公明, 水村和枝, 佐藤純, Masaki Mizuno
  • Organizer: 第75回日本体力医学会大会
• [Presentation] Insulin sensitizes the response to capsaicin in thin fiber muscle afferents and small dorsal root ganglion neurons in vitro. (2020)
  • Author(s): Amane Hori, Norio Hotta, Kimiaki Katanosaka, Kazue Mizumura, Jun Sato, Gary A. Iwamoto, Rie Ishizawa, Han-Kyul Kim, Wanpen Vongpatanasin, Jere H. Mitchell, Scott A. Smith, Masaki Mizuno
  • Organizer: The American Physiological Society’s (APS) Integrative Physiology of Exercise (IPE) 2020 conference
  • Int'l Joint Research
• [Presentation] マウス遅発性筋痛モデルにおける機械感受性TRPチャネルの関与 (2020)
  • Author(s): 太田大樹, 片野坂公明, 村瀬詩織, 加塩麻紀子, 富永真琴, 片野坂友紀, 田口徹, 水村和枝
  • Organizer: 第13回日本運動器疼痛学会
• [Presentation] 遅発性筋痛の分子機構：TRPA1およびTRPV2ノックアウトマウスを用いた解析 (2020)
  • Author(s): 太田大樹, 片野坂公明, 村瀬詩織, 加塩麻紀子, 富永真琴, 片野坂友紀, 田口徹, 水村和枝
  • Organizer: 第42回日本疼痛学会
• [Presentation] マウス遅発性筋痛モデルにおけるTRPチャネルの関与 (2020)
  • Author(s): 太田大樹, 片野坂公明, 村瀬詩織, 加塩麻紀子, 富永真琴, 片野坂友紀, 田口徹, 水村和枝
  • Organizer: 第25回日本基礎理学療法学術大会
• [Presentation] Responses to Mechanical and Chemical Stimuli are Augmented by Insulin Administration in Neurons Innervating Skeletal Muscle. (2019)
  • Author(s): Hotta N, Katanosaka K, Mizumura K, Mitchell JH, Smith SA, Mizuno M.
  • Organizer: EXPERIMENTAL BIOLOGY 2019
  • Int'l Joint Research
• [Presentation] Exploration of the molecular mechanisms of muscular adaptive responses: in the case of the repeated bout effect on exercise-induced muscle pain. (2019)
  • Author(s): Katanosaka K, HibinoY, Katanosaka Y,
  • Organizer: Gordon Research Conference, Muscle: Excitation-Contraction Coupling
  • Int'l Joint Research
• [Presentation] 遅発性筋痛におけるTRPA1チャネルの役割 (2019)
  • Author(s): 太田大樹、林功栄、加塩麻紀子、片野坂公明、村瀬詩織、富永真琴、田口徹、水村和枝、
  • Organizer: 日本筋学会第5回学術集会
• [Presentation] ラットおよびマウス遅発性筋痛モデルの機械痛覚過敏におけるTRPA1の関与 (2019)
  • Author(s): 太田大樹，林功栄，片野坂公明，村瀬詩織，加塩麻紀子，富永真琴，田口徹，水村和枝
  • Organizer: 第24回日本基礎理学療法学会
• [Presentation] The expression and distribution of mitsugumin53 in skeletal muscle, after lengthening contraction. (2019)
  • Author(s): Hibino Y, Katanosaka Y, Katanosaka K
  • Organizer: The 9th Federation of the Asian and Oceanian Physiological Societies Congress (FAOPS2019) in conjunction with the 96th Annual Meeting of The Physiological Society of Japan
  • Int'l Joint Research
• [Presentation] 高温感受性一次感覚ニューロンの同定に向けた免疫組織化学的解析 (2018)
  • Author(s): 片野坂公明
  • Organizer: 平成３０年度温熱生理研究会
• [Presentation] 骨格筋特異的TRPV2ノックアウトマウスを用いたメカニカルストレス応答の解析 (2018)
  • Author(s): 澁谷慎, 日比野雄平, 片野坂公明, 片野坂友紀
  • Organizer: 第6回若手による骨格筋細胞研究会
• [Presentation] Analysis of molecular mechanisms involved in mechanical adaptation of muscle and muscular pain after exercise. (2018)
  • Author(s): Katanosaka K, HibinoY, Katanosaka Y
  • Organizer: 第40回日本比較生理生化学会大会
• [Remarks] 中部大学，生命医科学科 研究成果と活動の紹介
  • URL: https://www3.chubu.ac.jp/medicine/news/24916/