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Development of a novel general anesthetic method of applying the enhancement of descending pain suppression system by stimulation of dopamine neurons of the nucleus accumbens

Research Project

Project/Area Number 18K09812
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionHiroshima University

Principal Investigator

Irifune Masahiro  広島大学, 医系科学研究科(歯), 教授 (10176521)

Co-Investigator(Kenkyū-buntansha) 兼松 隆  九州大学, 歯学研究院, 教授 (10264053)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsドパミン神経 / ドパミン受容体リガンド / カプサイシン / サブスタンスP / 脊髄後角 / 一次知覚神経終末 / スライス実験 / マイクロダイアリシス法 / 線条体 / オプトジェネティクス / GBR-12909 / メタンフェタミン / ホルマリンテスト / ドパミン受容体作動薬 / 全身麻酔要素 / 不動化 / エンケファリン遊離
Outline of Final Research Achievements

The intravenous anesthetic propofol did not inhibit pain induced by capsaicin via peripheral nociceptors in sedative state, but did inhibit during anesthesia. In formalin test, which produces comparatively chronic pain, we confirmed that selective dopamine re-uptake inhibitors suppressed formalin-induced pain, and that selective dopamine receptor antagonists reversed the analgesic effect of the inhibitors. These findings suggest that general anesthetics slightly inhibit descending pain suppression system, or do not affect it, and that stimulation of dopamine neurons are effective on surgical pain.

Academic Significance and Societal Importance of the Research Achievements

研究代表者のこれまでの研究で、中枢神経系における抑制性神経であるγ-アミノ酪酸(GABA)神経を内因性GABAにより刺激すると下行性鎮痛系が抑制されることを確認しているが、本研究では、GABA神経の促進により麻酔作用を生じると考えられている静脈麻酔薬のプロポフォールは、下行性鎮痛系の脊髄後角での作用部位である一次知覚神経終末からのサブスタンスP遊離実験により、下行性鎮痛系を軽度抑制するか、少なくとも増強しないことがわかった。また、選択的ドパミン取り込み阻害薬に鎮痛効果があることを明確にしたことから、本研究により、ドパミン神経作用薬は全身麻酔時の鎮痛薬として臨床応用可能であることが示唆された。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (20 results)

All 2020 2019 2018

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (11 results) (of which Int'l Joint Research: 3 results) Book (2 results)

  • [Journal Article] The indirect γ-aminobutyric acid (GABA) receptor agonist gabaculine-induced loss of the righting reflex may inhibit the descending analgesic pathway.2020

    • Author(s)
      Ogawa, Y., Irifune, M., Mukai, A., Shimizu, Y., Doi, M., Oue, K., Yoshida, M., Kanematsu, T., Morioka, M., Nakata, Y. and Sakai, N.
    • Journal Title

      Pharmacology Biochemistry and Behavior

      Volume: 198 Pages: 173034-173034

    • DOI

      10.1016/j.pbb.2020.173034

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Component of nicotine-induced intracellular calcium elevation mediated throughα3- andα5-containing nicotinic acetylcholine receptors are regulated by cyclic AMP in SH-SY 5Y cells2020

    • Author(s)
      Takahashi, T., Yoshida, T., Harada, K., Miyagi, T., Hashimoto, K., Hide, I., Tanaka, S., Irifune, M. and Sakai, N.
    • Journal Title

      PLos One

      Volume: 15 Issue: 11 Pages: e0242349-e0242349

    • DOI

      10.1371/journal.pone.0242349

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SKF-10047, a prototype Sigma-1 receptor agonist, augmented the membrane trafficking and uptake activity of the serotonin transporter and its C-terminus-deleted mutant via a Sigma-1 receptor-independent mechanism2019

    • Author(s)
      Asano Masaya、Motoike Serika、Yokota Chika、Usuki Naoto、Yamamoto Hikaru、Urabe Tomoaki、Katarao Kazusa、Hide Izumi、Tanaka Shigeru、Kawamoto Masashi、Irifune Masahiro、Sakai Norio
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 139 Issue: 1 Pages: 29-36

    • DOI

      10.1016/j.jphs.2018.11.005

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phospholipase C-related catalytically inactive protein: A novel signaling molecule for modulating fat metabolism and energy expenditure2019

    • Author(s)
      Kanematsu T, Oue K, Okumura T, Harada K, Yamawaki Y, Asano S, Mizokami A, Irifune M, Hirata M
    • Journal Title

      J Oral Biosci

      Volume: 61(2) Issue: 2 Pages: 65-72

    • DOI

      10.1016/j.job.2019.04.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Propofol induced diverse and subtype-specific translocation of PKC families.2018

    • Author(s)
      Miyahara T, Adachi N, Seki T, Hide I, Tanaka S, Saito N, Irifune M, Sakai N
    • Journal Title

      J. Pharmacol. Sci.

      Volume: 印刷中 Issue: 1 Pages: 20-29

    • DOI

      10.1016/j.jphs.2018.03.008

    • NAID

      120006488442

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effective Postoperative Analgesia Using Intravenous Flurbiprofen and Acetaminophen.2018

    • Author(s)
      Yoshida M, Shimizu Y, Yoshida K, Mukai A, Doi M, Irifune M.
    • Journal Title

      J Oral Maxillofac Surg

      Volume: 76(9) Issue: 9 Pages: 1869-1872

    • DOI

      10.1016/j.joms.2018.03.031

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Management of an Internal Carotid Artery Injury Caused by a Displaced Titanium Plate With a Combination of Interventional Vascular Radiology and Surgery2018

    • Author(s)
      Shimizu Y, Okazaki T, Hamana T, ando Irifune M
    • Journal Title

      Journal of Oral and Maxillofacial Surgery

      Volume: 76 Issue: 6 Pages: 1377.e1-1377.e4

    • DOI

      10.1016/j.joms.2018.02.006

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Perineural treatment with anti-HMGB1 antibody alleviates nociceptive-like behaviors in mice with chronic constriction injury of distal infraorbital nerve.2020

    • Author(s)
      Nakamura Y, Nakashima K, Liu K, Waki H, Nishibori M, Irifune M, Morioka N
    • Organizer
      The 93rd Annual Meeting of the Japanese Pharmacological Society
    • Related Report
      2020 Annual Research Report
  • [Presentation] Functional regulation of serotonin transporter by SNARE protein Syntaxin 3.2020

    • Author(s)
      Motoike S, Taguchi K, Urabe T, Harada K, Hide I, Tanaka S, Irifune M, Sakai N
    • Organizer
      The 93rd Annual Meeting of the Japanese Pharmacological Society
    • Related Report
      2020 Annual Research Report
  • [Presentation] ラット脊髄後角神経からのサブスタンスP遊離に及ぼす麻酔関連薬の影響:in vitroおよびin vivo実験による検討2020

    • Author(s)
      向井 友宏,佐々木 詩佳,今戸 瑛二, 入舩 正浩
    • Organizer
      第59回広島県歯科医学会・第104回広島大学歯学会例会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Perioperative anesthesia management for an autism spectrum disorder patient who was thought to be difficult to be hospitalized2019

    • Author(s)
      Oda A, Yoshida K, Kouch T, Mukai T, Kikuchi Y, Takahashi T, Yoshinaka T, Oue K, Mukai A, Shimizu C, Oda Y, Okada Y, Irifune M
    • Organizer
      The Asia Association for Disability and Oral Health
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The effect of tranexamic acid during sagittal split ramus osteotomy2019

    • Author(s)
      Yoshida M, Ono S, Shimizu Y, Yoshida K, Mukai A, Doi M, Irifune M
    • Organizer
      97th International Association for Dental Research General Session
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] GABA神経作動薬によるマウスの不動化は脳波解析による中枢神経抑制の強さと関係するか?-propofolとgabaculineの比較-2019

    • Author(s)
      入舩正浩,好中大雅,向井明里
    • Organizer
      第34回中国・四国歯科麻酔研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] GABA神経作動薬によるマウスの不動化は脳波解析による中枢神経抑制の強さとは無関係である2019

    • Author(s)
      好中大雅, 向井明里,入舩正浩
    • Organizer
      第46回日本歯科麻酔学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Prediction of prognosis following perioperative dental injury - comparison of anesthesiologists and dentists.2018

    • Author(s)
      Saeki N, Shimizu Y, Yoshida M, Yoshida K, Moriwaki N, Kawamoto M, Irifune M
    • Organizer
      The International Anesthesia Research Society (IARS) 2018 Annual Meeting and International Science Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] メタンフェタミンの鎮痛作用におけるノルアドレナリン神経の関与:ホルマリンテストによる検討2018

    • Author(s)
      小田 綾,入舩正浩
    • Organizer
      第33回中国・四国歯科麻酔研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] メタンフェタミンの鎮痛作用におけるドパミン神経の関与:ホルマリンテストによる検討2018

    • Author(s)
      小田 綾,入舩正浩
    • Organizer
      第46回日本歯科麻酔学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 各種神経作動薬による行動薬理作用と脳波・筋電位変化の関係解析2018

    • Author(s)
      菊池友香, 好中大雅, 入舩正浩
    • Organizer
      第46回日本歯科麻酔学会総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Book] 第8版 歯科麻酔学2019

    • Author(s)
      入舩正浩
    • Total Pages
      8
    • Publisher
      医歯薬出版株式会社
    • ISBN
      9784263458297
    • Related Report
      2019 Research-status Report
  • [Book] 第5版 臨床歯科麻酔学2019

    • Author(s)
      入舩正浩
    • Total Pages
      23
    • Publisher
      永末書店
    • ISBN
      9784816013560
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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