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慢性痛が睡眠・覚醒リズムに影響を与える神経科学的メカニズムの解明と治療法開発

Research Project

Project/Area Number 16K20085
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Anesthesiology
Research InstitutionUniversity of Toyama

Principal Investigator

伊東 久勝  富山大学, 附属病院, 助教 (60736388)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Discontinued (Fiscal Year 2018)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords疼痛学 / 神経科学 / 薬理学 / 麻酔科学
Outline of Annual Research Achievements

イソフルラン吸入による全身麻酔下にマウスの右側坐骨神経を半周結紮することによって、神経障害性疼痛モデルを作製した。Planter testおよびvon Freyvtestを用いて神経結紮手術7日後から熱痛覚過敏反応および機械的アロディニアが認められることを確認した。この神経障害性疼痛モデルに、全身麻酔下に脳波測定用ヘッドマウントを頭蓋骨にセメントで固定することで、無麻酔下に脳波を測定し、脳波解析ソフトSleep Signを用いて解析し睡眠状態を評価した。その結果、神経障害性疼痛モデルは覚醒期の増加、睡眠量の低下を認めた。さらに覚醒物質であるオレキシンの受容体拮抗薬であるDORA(Dual Orexine Receptor Antagonist)の投与を行い、神経障害性疼痛モデルの睡眠の改善が認められた。一方で、持続時間の長い睡眠の数が減少した。
DORAによる睡眠の改善が神経障害性疼痛に与える影響を調査するために、睡眠の改善が得られた投与量でDORAを神経結紮手術7日後から1週間投与後、Planter testおよびvon Frey testを用いて熱痛覚過敏反応および機械的アロディニアを評価した。その結果、DORA投与終了1時間後に疼痛行動の抑制が認められたが、24時間後には疼痛行動は対象マウスと同様のレベルまで戻った。また、回転カゴ付きケージを用いた自発運動の評価を行ったところ、DORA投与マウスは自発運動量
が低下する可能性が認められた。
そこでNaSSA(noradrenergic and specific serotonergic antidepressant)を用いて同様の実験を行ったところ、睡眠の改善が得られた。また熱痛覚過敏反応および機械的アロディニアを評価した結果、投与終了1時間後に疼痛行動の抑制が認められた。また、回転カゴ付きケージを用いた自発運動の評価を行ったところ、NaSSA投与マウスは自発運動量低下を認めなかった。

Report

(3 results)
  • 2018 Annual Research Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (4 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Transcatheter Aortic Valve Implantation Improves Cardiac Sympathetic Nerve Activity on <sup>123</sup>I-Metaiodobenzylguanidine Myocardial Scintigraphy in Severe Aortic Valve Stenosis2018

    • Author(s)
      Sobajima M, Ueno H, Onoda H, Kuwahara H, Tanaka S, Ushijima R, Fukuda N, Yokoyama S, Nagura S, Doi T, Yamashita A, Fukahara K, Ito H, Kinugawa K.
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 2 Pages: 579-585

    • DOI

      10.1253/circj.CJ-17-0817

    • NAID

      130006321857

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevalence of chronic postsurgical pain after thoracotomy and total knee arthroplasty: a retrospective multicenter study in Japan (Japanese Study Group of Subacute Postoperative Pain)2018

    • Author(s)
      Yoko Sugiyama, Hiroki Iida, Fumimasa Amaya, Kanako Matsuo, Yutaka Matsuoka, Keiko Kojima, Fumitaka Matsuno, Takayuki Hamaguchi, Masako Iseki, Keisuke Yamaguchi, Yoshika Takahashi, Atsuko Hara, Yusuke Sugasawa, Mikito Kawamata, Satoshi Tanaka, Yoshimi Inagaki, Akihiro Otsuki, Mitsuaki Yamazaki, Hisakatsu Ito
    • Journal Title

      Journal of Anesthesia

      Volume: - Issue: 3 Pages: 434-438

    • DOI

      10.1007/s00540-018-2481-0

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain2017

    • Author(s)
      Makino Hiroto、Seki Shoji、Yahara Yasuhito、Shiozawa Shunichi、Aikawa Yukihiko、Motomura Hiraku、Nogami Makiko、Watanabe Kenta、Sainoh Takeshi、Ito Hisakatsu、Tsumaki Noriyuki、Kawaguchi Yoshiharu、Yamazaki Mitsuaki、Kimura Tomoatsu
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1

    • DOI

      10.1038/s41598-017-17289-y

    • NAID

      120006542025

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Timed Inhibition of Orexin System by Suvorexant Improved Sleep and Glucose Metabolism in Type 2 Diabetic db/db Mice.2016

    • Author(s)
      Tsuneki H, Kon K, Ito H, Yamazaki M, Takahara S, Toyooka N, Ishii Y, Sasahara M, Wada T, Yanagisawa M, Sakurai T, Sasaoka T.
    • Journal Title

      Endocrinology.

      Volume: 157 Issue: 11 Pages: 4146-4157

    • DOI

      10.1210/en.2016-1404

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Effects of suvorexant on sleep condition in a mouse model of neuropathic pain.2017

    • Author(s)
      Hisakatsu Itoa, Yoshinori Takemuraa, Mizuki Hattoria, Masaaki Kawakamia, Hiroshi Tsunekib, Toshiyasu Sasaokab, Mitsuaki Yamazaki
    • Organizer
      6th International Congress on Neuropathic Pain
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Influences of the sleep improvement by suvorexant on pain behavior and voluntary activity in neuropathic pain model2017

    • Author(s)
      Hisakatsu Ito, Mizuki Hattori, Masaaki Kawakami, Akiyo Kameyama, Mitsuaki Yamazaki
    • Organizer
      Anesthesiology 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of suvorexant on secondary sleep disturbance induced by chronic neuropathic pain2016

    • Author(s)
      Hisakatsu Ito, Yuta Aoki, Yoshinori Takemura, Mitsuaki Yamazaki
    • Organizer
      16th World Congress on Pain
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of Suvorexant on the sleep disturbance in leptin-resistant (db/db) genetically obese and diabetic mice2016

    • Author(s)
      Hisakatsu Ito, Hiroshi Tsuneki, Kanta Kon, Toshiyasu Sasaoka, Naoki Toyooka, Yoshinori Takemura, Mitsuaki Yamazaki
    • Organizer
      10th Forum of Neuroscience
    • Place of Presentation
      Copenhagen, Denmark
    • Year and Date
      2016-07-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-12-27  

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