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内臓痛の鎮痛適応を起こす神経回路シフト

Publicly Offered Research

Project AreaMechanisms underlying the functional shift of brain neural circuitry for behavioral adaptation
Project/Area Number 17H05547
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTohoku University

Principal Investigator

福土 審  東北大学, 医学系研究科, 教授 (80199249)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywordsストレス / 内臓感覚 / 神経伝達 / 受容体 / 刺激プログラム
Outline of Annual Research Achievements

国民の健康を左右する要因として内臓感覚の比重が急激に高まっている。その代表的な病態が過敏性腸症候群である。本研究は、内臓痛の鎮痛適応を生み出す脳内神経伝達を明らかにする。これを脳機能画像の手法を中心に行う。具体的には、健常者と過敏性腸症候群患者を対象とする。方法としてヒスタミンH1受容体リガンド11C-doxepinとドパミンD2受容体リガンド11C-racloprideを用い、陽電子断層法(PET)を中心とする脳画像を得る。本年度は主に11C- doxepinについて研究を進捗させた。目的は、過敏性腸症候群においては脳内ヒスタミン神経伝達が低下している、という仮説を検証した。対象は健常者(n=20,男性10, 女性10)ならびにIBS (n=20, 男性10, 女性10)。標識体11C -doxepinを静注し、3次元デ-タ収集モ-ドにて11C-doxepin-H1受容体結合を測定した。またPET検査中の情動はordinate scaleで定量化した。分析は、得られたPET画像を動態解析ソフトウェアPMODで処理し、ROI解析にて受容体結合能を定量化した。その後、統計解析ソフトウェアSPSSにて男女および健常者群IBS群の4群にて比較検討した。結果は左扁桃体、右中帯状回、左右尾状核、左右視床、左海馬にて、有意な男女x健常IBS交互作用を認めた(two-way ANOVA)。健常女性と健常男性で、左右視床、左右海馬、左尾状核と左扁桃体に有意差を認め、女性がより高値であった(Bonferroni解析)。また、健常者性別間で有意差のあったヒスタミン受容体結合能が、IBS群では、男女の有意差が消失していた。健常女性に比して、IBS男性は左右視床、右レンズ核、左右海馬で有意差を認め、IBS女性は、左右視床、左右尾状核、右レンズ核、左海馬で有意差を認めた。本研究により、健常者には脳内ヒスタミン受容体結合能に性差があることを再現した。また、IBS患者では、脳内ヒスタミン受容体結合能の性差が、健常者とは異なっていることが示唆された。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (27 results)

All 2019 2018 2017 Other

All Int'l Joint Research (6 results) Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (10 results) (of which Int'l Joint Research: 10 results,  Invited: 9 results) Book (4 results) Remarks (1 results)

  • [Int'l Joint Research] University of North Carolina/Rome Foundation(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Leuven(ベルギー)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Tubingen(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of North Carolina/Rome Foundation/University of California, Los Angeles(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Leuven(ベルギー)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Tubingen(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] A randomized controlled and long-term linaclotide study of irritable bowel syndrome with constipation patients in Japan2018

    • Author(s)
      Fukudo Shin、Miwa Hiroto、Nakajima Atsushi、Haruma Ken、Kosako Masanori、Nakagawa Ayako、Akiho Hiraku、Yamaguchi Yusuke、Johnston Jeffrey M.、Currie Mark、Kinoshita Yoshikazu
    • Journal Title

      Neurogastroenterology & Motility

      Volume: 30 Issue: 12

    • DOI

      10.1111/nmo.13444

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Understanding Neurogastroenterology From Neuroimaging Perspective: A Comprehensive Review of Functional and Structural Brain Imaging in Functional Gastrointestinal Disorders2018

    • Author(s)
      Kano Michiko、Dupont Patrick、Aziz Qasim、Fukudo Shin
    • Journal Title

      Journal of Neurogastroenterology and Motility

      Volume: 24 Issue: 4 Pages: 512-527

    • DOI

      10.5056/jnm18072

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of attention bias modification on event-related potentials in patients with irritable bowel syndrome: A preliminary brain function and psycho-behavioral study2018

    • Author(s)
      Tayama J.、Saigo T.、Ogawa S.、Takeoka A.、Hamaguchi T.、Inoue K.、Okamura H.、Yajima J.、Matsudaira K.、Fukudo S.、Shirabe S.
    • Journal Title

      Neurogastroenterology & Motility

      Volume: 30 Issue: 10

    • DOI

      10.1111/nmo.13402

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized, double-blind, placebo-controlled study.2018

    • Author(s)
      Fukudo S, Nakajima A, Fujiyama Y, Kosako M, Nakagawa A, Akiho H, Nakashima Y, Johnston JM, Miwa H.
    • Journal Title

      Neurogastroenterol Motil

      Volume: - Issue: 5

    • DOI

      10.1111/nmo.13275

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Influence of uncertain anticipation on brain responses to aversive rectal distension in patients with irritable bowel syndrome.2017

    • Author(s)
      Kano M, Muratsubaki T, Morishita J, Kono K, Mugikura S, Takase K, Ly HG, Dupont P, Van Oudenhove L, Fukudo S.
    • Journal Title

      Psychosom Med

      Volume: 79 Issue: 9 Pages: 988-999

    • DOI

      10.1097/psy.0000000000000484

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of attention bias modification on brain function and anxiety in patients with irritable bowel syndrome: A preliminary electroencephalogram and psycho-behavioral study.2017

    • Author(s)
      Tayama J, Saigo T, Ogawa S, Takeoka A, Hamaguchi T, Hayashida M, Fukudo S, Shirabe S.
    • Journal Title

      Neurogastroenterol Motil

      Volume: 29 Issue: 12 Pages: 1-10

    • DOI

      10.1111/nmo.13131

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Impact of stress on brain-gut interactions in irritable bowel syndrome.2018

    • Author(s)
      Shin Fukudo.
    • Organizer
      The Summer School on Stress: From Hans Selye’s original concept to recent advances 2018. Conrad Osaka, Osaka, Japan.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of brain-gut axis in irritable bowel syndrome. Symposium: Brain-gut axis.2018

    • Author(s)
      Shin Fukudo.
    • Organizer
      The 18th World Congress of Basic and Clinical Pharmacology. Kyoto International Conference Center, Kyoto, Japan.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Psychosomatic approach for irritable bowel syndrome. Symposium: IBS: Update in 2018.2018

    • Author(s)
      Shin Fukudo.
    • Organizer
      The Asian Pacific Digestive Disease Week, Seoul, Korea.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Bacterial Dysbiosis. Symposium: Functional Aspects of Host-Microbiome Interactions.2018

    • Author(s)
      Shin Fukudo.
    • Organizer
      The 3rd Meeting of the International Federation of Neurogastroenterology and Motility and Postgraduate Course of Gastrointestinal Motility. RAI Convention Center, Amsterdam, Netherland.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Efficacy and Safety of Novel 5-HT4 Agonist DSP-6952 in Patients with Irritable Bowel Syndrome with Constipation: A Randomized, Double-Blind, Placebo-Controlled Early Phase II Study.2018

    • Author(s)
      Shin Fukudo, Masatoshi Nakamura, Hiroto Miwa.
    • Organizer
      The 119th Annual Meeting of American Gastroenterological Association, Washington DC, USA.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Invited Lecture: Novel Concepts in Sensory Neurobiology. Research Forum: Novel Concepts in Sensory Neurobiology.2017

    • Author(s)
      Shin Fukudo
    • Organizer
      The 118th Annual Meeting of the American Gastroenterological Association, Chicago, IL, USA, May 9, 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Invited Lecture: Gut Microbiota in Irritable Bowel Syndrome.2017

    • Author(s)
      Shin Fukudo
    • Organizer
      Symposium of Advanced Image and Gut Microbiota. Meeting Room of GI Division (12F), Taipei Veterans General Hospital, Taipei, Twawan, June 9, 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Invited Lecture: The Role of Gut Microbiota and Brain Function in Irritable Bowel Syndrome. Gut Microbiota and Human Diseases.2017

    • Author(s)
      Shin Fukudo
    • Organizer
      Annual Meeting of the Chinese Medical Association, Taipei, Twawan, June 10, 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Invited Lecture: Management of Diarrhea Predominant Irritable Bowel Syndrome: An Asian Perspective.2017

    • Author(s)
      Shin Fukudo
    • Organizer
      Symposium on Management of Irritable Bowel Syndrome. Chennai, India, November 17, 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Invited Lecture: Management of Diarrhea Predominant Irritable Bowel Syndrome: An Asian Perspective.2017

    • Author(s)
      Shin Fukudo
    • Organizer
      Symposium on Management of Irritable Bowel Syndrome. Kolkata, India, November 18, 2017.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] ストレスと上部・下部消化管症状 ― 心療内科的アプローチと診察入門. 榊原隆次, 福土審, 編集. 神経・精神疾患による消化管障害. ベッドサイドマニュアル.2019

    • Author(s)
      福土審.
    • Total Pages
      379
    • Publisher
      中外医学社, 東京
    • ISBN
      9784498140486
    • Related Report
      2018 Annual Research Report
  • [Book] Psycho-gastroenterology. In; Tominaga K, Kusunoki H. Functional dyspepsia. Evidences in Pathophysiology and Treatment.2018

    • Author(s)
      Shoji T, Endo Y, Fukudo S.
    • Total Pages
      187
    • Publisher
      Springer Nature Singapore Pte Ltd, Singapore.
    • Related Report
      2018 Annual Research Report
  • [Book] 過敏性腸症候群. 福井次矢, 高木誠, 小室一成総編集. 今日の治療指針.2018

    • Author(s)
      福土審
    • Publisher
      医学書院, 東京
    • ISBN
      9784260032339
    • Related Report
      2017 Annual Research Report
  • [Book] 過敏性腸症候群. 矢崎義男総編集: 内科学, 第11版2017

    • Author(s)
      福土審
    • Publisher
      朝倉書店, 東京
    • Related Report
      2017 Annual Research Report
  • [Remarks] 東北大学病院心療内科

    • URL

      http://www.hosp.tohoku.ac.jp/sinryou/s08_sinryou.html

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-12-28  

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