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The development of optogenetics-induced neuropathic pain model mice and the elucidation of pain mechanism

Research Project

Project/Area Number 21K08925
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionUniversity of Miyazaki

Principal Investigator

Maruta Toyoaki  宮崎大学, 医学部, 講師 (20363591)

Co-Investigator(Kenkyū-buntansha) 黒木 未央  宮崎大学, 医学部, 技能補佐員 (90706483)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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疼痛 / 神経障害性疼痛 / ナトリウムチャネル / Nav1.7 / Nav1.8 / Nav1.9 / オプトジェネティクス / 脊髄後根神経節 / 電位依存性ナトリウムチャネル / NaV1.7 / NaV1.8 / NaV1.9 / 脊髄後根神経 / マウス
Outline of Research at the Start

申請者は青色光照射で疼痛行動を起こすNaV1.7-ChR2マウス、NaV1.8-ChR2マウス、NaV1.9-ChR2マウスを独自に作製している。本研究では、これらの遺伝子組換えマウスを用いて、青色光を足底に長時間光照射して神経障害性疼痛モデルマウスを作製し、神経障害性疼痛発症におけるそれぞれの電位依存性Na+チャネルの関わりや細胞内機序を解明する。

Outline of Final Research Achievements

The applicant has applied optogenetics to pain research and developed light-responsive pain mice (three strains: NaV1.7-ChR2, NaV1.8-ChR2 and NaV1.9-ChR2 mice). In this study, a neuropathic pain model was created in these light-responsive pain mice by specifically and continuously excitating nerve fibres in which each voltage-gated Na+ channel was expressed by prolonged light exposure, and an increase in c-Fos positive cells was observed in the dorsal horn of the spinal cord.

Academic Significance and Societal Importance of the Research Achievements

神経障害性疼痛の発症機序は複雑で、それが機序解明と根本治療の確立を難しくしている。申請者が開発した光応答性疼痛マウスに光照射することで作製した神経障害性疼痛モデルは、外科的侵襲なしに、痛みを司る神経自体を刺激するというシンプルな方法で作製している。そのため、このモデルを使用すると神経障害性疼痛での細胞内における発症メカニズムを正確に解明することがで切ると考えている。そして、根本的な発症機序を解明できれば、神経障害性疼痛の治療法確立につながることが期待される。

Report

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

    (18 results)

All 2023 2022 2021 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (6 results) (of which Invited: 1 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Changes in TRPV1 Receptor, CGRP, and BDNF Expression in Rat Dorsal Root Ganglion with Resiniferatoxin-Induced Neuropathic Pain: Modulation by Pulsed Radiofrequency Applied to the Sciatic Nerve2023

    • Author(s)
      Koshida T., Maruta T., Tanaka N., Hidaka K., Kurogi M., Nemoto T., Yanagita T., Takeya R., Tsuneyoshi I.
    • Journal Title

      Acta Medica Okayama

      Volume: 77 Issue: 4 Pages: 359-364

    • DOI

      10.18926/AMO/65741

    • URL

      https://ousar.lib.okayama-u.ac.jp/65741

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epidural Anesthesia and Continuous Epidural Analgesia in a Pediatric Patient With Pelizaeus-Merzbacher Disease: A Case Report.2022

    • Author(s)
      Toyoaki Maruta, Yumi Watanabe, Yukiko Nagata, Rina Kashino, Isao Tsuneyoshi
    • Journal Title

      Cureus

      Volume: 14

    • DOI

      10.7759/cureus.29983

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selective optogenetic activation of NaV1.7-expressing afferents in NaV1.7-ChR2 mice induces nocifensive behavior without affecting responses to mechanical and thermal stimuli.2022

    • Author(s)
      Toyoaki Maruta, Kotaro Hidaka, Satoshi Kouroki, Tmohiro Koshida, Mio Kurogi, Yohko Kage, Seiya Mizuno, Tetsuro Shirasaka, Toshihiko Yanagita, Satoru Takahashi, Ryu Takeya, Isao Tsuneyoshi
    • Journal Title

      PLoS One

      Volume: 17 Issue: 10 Pages: e0275751-e0275751

    • DOI

      10.1371/journal.pone.0275751

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular signal-regulated kinase phosphorylation enhancement and Na V 1.7 sodium channel upregulation in rat dorsal root ganglia neurons contribute to resiniferatoxin-induced neuropathic pain: The efficacy and mechanism of pulsed radiofrequency therapy2022

    • Author(s)
      Kotaro Hidaka, Toyoaki Maruta, Tomohiro Koshida, Mio Kurogi, Yohko Kage, Satoshi Kouroki, Tetsuro Shirasaka, Ryu Takeya, Isao Tsuneyoshi
    • Journal Title

      Molecular pain

      Volume: 18 Pages: 1-12

    • DOI

      10.1177/17448069221089784

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Satoshi Kouroki, Toyoaki Maruta, Isao Tsuneyoshi2022

    • Author(s)
      Effect of cryoprecipitate on an increase in fibrinogen level in patients with excessive intraoperative blood loss: a single-center retrospective study
    • Journal Title

      JA clinical reports

      Volume: 8 Issue: 1 Pages: 27-27

    • DOI

      10.1186/s40981-022-00516-5

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The diagnostic and prognostic value of mature and total adrenomedullin for sepsis: a prospective observational study2021

    • Author(s)
      Tetsu Yonaha, Toyoaki Maruta, Go Otao, Koji Igarashi, Sayaka Nagata, Takeshi Yano, Masahiko Taniguchi, Kazuo Kitamura, Isao Tsuneyoshi
    • Journal Title

      Anaesthesiology intensive therapy

      Volume: 53 Issue: 5 Pages: 411-417

    • DOI

      10.5114/ait.2021.111345

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The usefulness of plasma levels of mature and total adrenomedullin as biomarkers indicating the magnitude of surgical stress responses: A single-center, prospective, observational study2021

    • Author(s)
      Go Otao, Toyoaki Maruta, Tetsu Yonaha, Koji Igarashi, Sayaka Nagata, Kazuo Kitamura, Isao Tsuneyoshi
    • Journal Title

      Journal of translational research

      Volume: 7 Pages: 302-310

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of opioid local anesthetic combination regimens using the number of self-administrated boluses in patient-controlled epidural analgesia after cesarean section: A retrospective single-center study2021

    • Author(s)
      Go Otao, Toyoaki Maruta, Isao Tsuneyoshi
    • Journal Title

      Medicine

      Volume: 100 Issue: 17 Pages: e25560-e25560

    • DOI

      10.1097/md.0000000000025560

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 光応答性疼痛モデルマウスを用いた疼痛研究2023

    • Author(s)
      丸田豊明、興梠聡志、日髙康太郎、武谷立、恒吉勇男
    • Organizer
      第7回 黒潮カンファレンス
    • Related Report
      2023 Annual Research Report
  • [Presentation] 光を当てると痛がる!? ~オプトジェネティクスを応用した新規疼痛モデル動物の模索~2023

    • Author(s)
      丸田豊明
    • Organizer
      第13回 トランスポーター研究会九州部会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] パルス高周波療法によるTRPV1、CGRP、BDNFの変化:レシニフェラトキシン誘発性疼痛ラット脊髄後根神経節での検討2022

    • Author(s)
      越田智広、丸田豊明、日髙康太郎、興梠聡志、恒吉勇男
    • Organizer
      第44回日本疼痛学会
    • Related Report
      2022 Research-status Report
  • [Presentation] オプトジェネティクスを用いた光による痛み制御:ナトリウムチャネルNaV1.7・ NaV1.8・NaV1.9を標的とした遺伝子改変マウスの開発と疼痛行動の比較2022

    • Author(s)
      丸田豊明、興梠聡志、日髙康太郎、越田智広、白阪哲朗、恒吉勇男
    • Organizer
      第69回日本麻酔科学会
    • Related Report
      2022 Research-status Report 2021 Research-status Report
  • [Presentation] 帯状疱疹後神経痛モデルラットにおける高周波パルス療法の作用機序の検討2021

    • Author(s)
      日高康太郎、丸田豊明、越田智広、興梠聡志、白阪哲朗、恒吉勇男
    • Organizer
      第43回日本疼痛学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Resiniferatoxin誘発性疼痛ラットでのTramadol治療後の高周波パルス療法の有効性と作用機序の検討2021

    • Author(s)
      ○日高康太郎、丸田豊明、門田瑤子、興梠聡志、越田智広、渡部由美、山賀昌治、恒吉勇男
    • Organizer
      第55回日本ペインクリニック学会
    • Related Report
      2021 Research-status Report
  • [Book] くすりがわかる 作用機序×使い方×観察・ケア2023

    • Author(s)
      柳田俊彦 他
    • Total Pages
      452
    • Publisher
      南山堂
    • ISBN
      9784525500719
    • Related Report
      2023 Annual Research Report
  • [Book] 麻酔科トラブルシューティング A to Z 第2版2022

    • Author(s)
      丸田豊明、他
    • Total Pages
      629
    • Publisher
      文光堂
    • ISBN
      9784830628535
    • Related Report
      2022 Research-status Report
  • [Remarks] 研究内容

    • URL

      http://www.med.miyazaki-u.ac.jp/home/masui/research/researchcontent/

    • Related Report
      2021 Research-status Report
  • [Remarks] 研究業績

    • URL

      http://www.med.miyazaki-u.ac.jp/home/masui/research/performance/

    • Related Report
      2021 Research-status Report

URL: 

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

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