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Elucidation of Endogenous Oxytocin's Pain Perception and Modulation Mechanisms by using Artificial Receptor Gene

Research Project

Project/Area Number 21K06779
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

Yoshimura Mitsuhiro  産業医科大学, 医学部, 訪問研究員 (00464462)

Co-Investigator(Kenkyū-buntansha) 上田 陽一  産業医科大学, 医学部, 教授 (10232745)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsオキシトシン / DREADDs / トランスジェニックラット / 疼痛 / 抗炎症 / 化学遺伝学的手法 / 下行性疼痛抑制系 / 疼痛制御
Outline of Research at the Start

近年、薬剤受容体を用いて特定のニューロンを特異的に活性化させる手法(DREADDs)が開発された。我々は、この手法を応用したトランスジェニックラットを作出した。本研究の目的は、オキシトシン(OXT)-hM3Dq-mCherryトランスジェニックラットを用いて、(1)内因性OXTの末梢・中枢における疼痛受容・調節メカニズムを解明すること、(2)種々の疼痛・炎症モデルラットを作成して内因性OXTの鎮痛・抗炎症メカニズムを明らかにすることである。

Outline of Final Research Achievements

Oxytocin is a hormone known for its involvement in physiological processes such as childbirth and lactation. Recent studies suggest its involvement in pain. Using genetically modified rats with artificially inserted receptor genes, we have demonstrated the significant role of oxytocin in pain perception and modulation. Activation of oxytocin neurons was shown to activate the descending pain inhibitory system centrally, suppressing sensory transmission, and inhibiting mast cell degranulation peripherally to alleviate local inflammation, resulting in a reduction in pain perception.

Academic Significance and Societal Importance of the Research Achievements

この研究は、オキシトシンが痛み知覚と調節に重要な役割を果たすことを内因性のオキシトシンニューロンを活性化させる手法を用いて直接的に証明したものである。したがって、新たな疼痛治療法の開発や、疼痛管理の向上につながる可能性を秘めている。これらの研究成果は、これまでにない視点から身体的なプロセスを理解する手掛かりとなり、神経科学分野における基礎研究、ひいては臨床応用を見据えた橋渡し研究に貢献する。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (22 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (3 results) Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (13 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] University of Bristol(英国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] University of Bristol(英国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] University of Bristol(英国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Chemogenetic Activation of Oxytocin Neurons Improves Pain in a Reserpine-induced Fibromyalgia Rat Model2023

    • Author(s)
      Ikeda N、Kawasaki M、Baba K、Nishimura H、Fujitani T、Suzuki H、Matsuura T、Ohnishi H、Shimizu M、Sanada K、Nishimura K、Yoshimura M、Maruyama T、Conway-Campbell Becky L、Onaka T、Teranishi H、Hanada R、Ueta Y、Sakai A
    • Journal Title

      Neuroscience

      Volume: 528 Pages: 37-53

    • DOI

      10.1016/j.neuroscience.2023.07.028

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phase-shifting the circadian glucocorticoid profile induces disordered feeding behaviour by dysregulating hypothalamic neuropeptide gene expression2023

    • Author(s)
      Yoshimura Mitsuhiro、Flynn Benjamin P.、Kershaw Yvonne M.、Zhao Zidong、Ueta Yoichi、Lightman Stafford L.、Conway-Campbell Becky L.
    • Journal Title

      Communications Biology

      Volume: 6 Issue: 1

    • DOI

      10.1038/s42003-023-05347-3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deschloroclozapine exhibits an exquisite agonistic effect at lower concentration compared to clozapine-N-oxide in hM3Dq expressing chemogenetically modified rats2023

    • Author(s)
      Shimizu Makiko、Yoshimura Mitsuhiro、Baba Kazuhiko、Ikeda Naofumi、Nonaka Yuki、Maruyama Takashi、Onaka Tatsushi、Ueta Yoichi
    • Journal Title

      Frontiers in Neuroscience

      Volume: 17

    • DOI

      10.3389/fnins.2023.1301515

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats2022

    • Author(s)
      Nishimura Haruki and Yoshimura Mitsuhiro et al.
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 907-907

    • DOI

      10.1038/s42003-022-03879-8

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chemogenetic activation of endogenous arginine vasopressin exerts anorexigenic effects via central nesfatin-1/NucB2 pathway2021

    • Author(s)
      Sanada Kenya、Yoshimura Mitsuhiro、Ikeda Naofumi、Baba Kazuhiko、Nishimura Haruki、Nishimura Kazuaki、Nonaka Yuki、Maruyama Takashi、Miyamoto Tetsu、Mori Masatomo、Conway-Campbell Becky、Lightman Stafford、Kataoka Masaharu、Ueta Yoichi
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 71 Issue: 1 Pages: 18-18

    • DOI

      10.1186/s12576-021-00802-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Arginine vasopressin: Direct and indirect action on metabolism2021

    • Author(s)
      Yoshimura Mitsuhiro、Conway-Campbell Becky、Ueta Yoichi
    • Journal Title

      Peptides

      Volume: 142 Pages: 170555-170555

    • DOI

      10.1016/j.peptides.2021.170555

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] オキシトシンとバソプレシンの行動における役割2024

    • Author(s)
      吉村 充弘
    • Organizer
      第101回日本生理学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] オキシトシンの鎮痛・抗炎症効果2023

    • Author(s)
      吉村 充弘
    • Organizer
      第49回日本神経内分泌学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ストレス負荷時のオキシトシンの役割2023

    • Author(s)
      漆葉 美佳、 吉村 充弘、安部 力、椎名 貴彦、志水 泰武、上田 陽一
    • Organizer
      第41回産業医科大学学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects via neuronal and humoral pathways in rats2022

    • Author(s)
      Mitsuhiro Yoshimura, Haruki Nishimura, Kenya Sanada, Satomi Sonoda, Kazuaki Nishimura, Kazuhiko Baba, Naofumi Ikeda, Takashi Maruyama, Yuki Nonaka, Ryoko Baba, Tatsushi Onaka, Takafumi Horishita, Hiroyuki Morimoto, Yasuhiro Yoshida, Makoto Kawasaki, Akinori Sakai, Becky Conway-Campbell, Stafford Lightman, Yoichi Ueta
    • Organizer
      第95回日本内分泌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Endogenous oxytocin alleviated nociceptive response by altering gene expression in the spinal dorsal horn2022

    • Author(s)
      Mitsuhiro Yoshimura, Haruki Nishimura, Kenya Sanada, Satomi Sonoda, Kazuaki Nishimura, Kazuhiko Baba, Naofumi Ikeda, Takashi Maruyama, Yuki Nonaka, Ryoko Baba, Tatsushi Onaka, Takafumi Horishita, Hiroyuki Morimoto, Yasuhiro Yoshida, Makoto Kawasaki, Akinori Sakai, Becky Conway-Campbell, Stafford Lightman, Yoichi Ueta
    • Organizer
      The International Congress of Neuroendocrinology
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] オキシトシンは鎮痛効果および抗炎症効果をもつ2022

    • Author(s)
      吉村充弘、西村春来、野中有紀、馬場良子、森本景之、吉田安宏、堀下貴文、尾仲達史、村谷匡史、川﨑 展、酒井昭典、上田陽一
    • Organizer
      第40回産業医科大学学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects via neuronal and humoral pathways in rats2022

    • Author(s)
      Nishimura H, Yoshimura M, Sanada K, Sonoda S, Nishimura K, Baba K, Ikeda N, Maruyama T, Nonaka Y, Baba R, Onaka T, Horishita T, Morimoto H, Yoshida Y, Kawasaki M, Sakai A, Conway-Campbell B, Lightman S and Ueta Y
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] ラット内因性オキシトシンは疼痛抑制・抗炎症効果を有する2022

    • Author(s)
      吉村充弘、西村春来、尾仲達史、上田陽一
    • Organizer
      第30回日本病態生理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] ラットアルギニンバソプレシンニューロンの化学遺伝学的活性化によって 惹起される摂食抑制への中枢性Nesfatin-1/NucB2経路の関与2022

    • Author(s)
      眞田 賢哉、吉村 充弘、清水 真喜子、池田 直史、馬場 一彦、丸山崇、宮本 哲、片岡 雅晴、上田 陽一
    • Organizer
      第31回バソプレシン研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] Chemogenetic activation of endogenous arginine vasopressin exerts anorexigenic effect via central nesfatin-1/NucB2 pathway2021

    • Author(s)
      Kenya Sanada, Mitsuhiro Yoshimura, Naofumi Ikeda, Kazuhiro Baba, Haruki Nishimura, Kazuaki Nishimura, Yuki Nonaka, Takashi Maruyama, Tetsu Miyamoto, Masatomo Mori, Becky Conway-Campbell, Stafford Lightman, Masaharu Kataoka, and Yoichi Ueta
    • Organizer
      第39回産業医科大学学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 両側卵巣摘出ラットにおけるオキシトシンの疼痛閾値への関与の検討2021

    • Author(s)
      清水真喜子、池田直史、馬場一彦、眞田賢哉、吉村充弘、丸山崇、上田陽一
    • Organizer
      第48回自律神経生理研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] レセルピン反復投与誘発線維筋痛症モデルラットにおける痛覚反応・うつ状態の評価及びオキシトシン系活性化2021

    • Author(s)
      池田直史、川崎展、清水真喜子、馬場一彦、西村春来、眞田賢哉、西村和朗、鈴木仁士、吉村充弘、丸山崇、上田陽一、酒井昭典
    • Organizer
      第72回西日本生理学会
    • Related Report
      2021 Research-status Report
  • [Presentation] ラットアルギニンバソプレシンニューロンの化学遺伝学的活性化によって惹起される摂食抑制への中枢性Nesfatin-1/NucB2経路の関与2021

    • Author(s)
      眞田賢哉、吉村充弘、清水真喜子、池田直史、馬場一彦、丸山崇、宮本哲、片岡雅晴、上田陽一
    • Organizer
      第74回日本自律神経学会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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