Central biomarker of functional pain disorders

• Project/Area Number: 26460898
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Tohoku University
• Principal Investigator: Kano Michiko 東北大学, 学際科学フロンティア研究所, 助教 (20344658)
• Co-Investigator(Renkei-kenkyūsha): FUKUDO Shin 東北大学, 医学系研究科, 教授 (80199249) ; KANAZAWA Motoyori 東北大学, 医学系研究科, 准教授 (70323003)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 内臓痛 / 予期不安 / 過敏性腸症候群 / 脳画像 / 島皮質 / 内臓感覚 / 機能性疼痛障害 / 中枢性感作 / ストレス応答 / 脳腸相関 / 機能性磁気共鳴装置 / 機能性疼痛 / 機能性消化管障害 / 心身症 / 国際研究者支援 / 脳機能 / 国際研究者交流 / 大腸伸展刺激

Outline of Final Research Achievements

One of the main pathophysiology of functional pain disorders is suggested as the disorders of central pain processing. In this study, we investigated that the brain processing of visceral stimulation in participants with irritable bowel syndrome (IBS) who are suffering from chronic abdominal pain and change of bowel habit. Visual cues informed the possibility of upcoming visceral stimulation. Participates with IBS demonstrated that increased brain activity in the anterior midcingulate cortex and posterior cingulate cortex during visceral stimulation after uncertain cue than that after certain cue. In addition, IBS participants failed to reduce the activation in the insula cortex during safe condition. This results indicate that the context of anticipation influence the brain processing of visceral pain and which may contribute to pain symptoms in patients with IBS.

Research Products

• [Int'l Joint Research] ルーベン大学/TARGID(ベルギー)
• [Int'l Joint Research] グレノブル大学/神経科学研究所(フランス)
• [Int'l Joint Research] コロラド大学/the Institute for Cognitive Science(米国)
• [Int'l Joint Research] クィーンメリー大学/Wingate Institute(英国)
• [Int'l Joint Research] キングスカレッジロンドン/Institute of Psychiatry(英国)
• [Int'l Joint Research] KU Leuven(Belgium)
• [Int'l Joint Research] Grenoble Institut des Neurosciences(France)
• [Int'l Joint Research] University of Colorado, Boulder(米国)
• [Int'l Joint Research] University Medicine Greifswald,(ドイツ)
• [Int'l Joint Research] Wingate Institute(英国)
• [Int'l Joint Research] Cognitive and Affective/Neuroscience Laboratory/University of Colorado, Boulder(米国)
• [Int'l Joint Research] Translational Research Center/for Gastrointestinal Disorders (TARGID)/University of Leuven (Belgium)
• [Int'l Joint Research] Grenoble Institut des Neurosciences(France)
• [Journal Article] Generalizable representations of pain, cognitive control, and negative emotion in medial frontal cortex (2018)
  • Author(s): Kragel Philip A.、Kano Michiko、Van Oudenhove Lukas、Ly Huynh Giao、Dupont Patrick、Rubio Amandine、Delon-Martin Chantal、Bonaz Bruno L.、Manuck Stephen B.、Gianaros Peter J.、Ceko Marta、Reynolds Losin Elizabeth A.、Woo Choong-Wan、Nichols Thomas E.、Wager Tor D.
  • Journal Title: Nature Neuroscience Volume: 21 Issue: 2 Pages: 283-289
  • DOI: 10.1038/s41593-017-0051-7
• [Journal Article] Brain responses to vestibular pain and its anticipation in women with Genito-Pelvic Pain/Penetration Disorder (2017)
  • Author(s): Pazmany Els、Ly Huynh Giao、Aerts Leen、Kano Michiko、Bergeron Sophie、Verhaeghe Johan、Peeters Ronald、Tack Jan、Dupont Patrick、Enzlin Paul、Van Oudenhove Lukas
  • Journal Title: Neuroimage: Clinical Volume: 16 Pages: 477-490
  • DOI: 10.1016/j.nicl.2017.07.017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Altered brain and gut responses to corticotropin-releasing hormone (CRH) in patients with irritable bowel syndrome. (2017)
  • Author(s): Kano M, Muratsubaki T, Van Oudenhove L, Morishita J, Yoshizawa M, Kohno K, Yagihashi M, Tanaka Y, Mugikura S, Dupont P, Ly HG, Takase K, Kanazawa M, Fukudo S.
  • Journal Title: Sci Rep Volume: 29 Issue: 1 Pages: 12425-12425
  • DOI: 10.1038/s41598-017-09635-x
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Influence of uncertain anticipation on brain responses to aversive rectal distension in subjects 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: Psychosomatic Medicine Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 機械学習によるニューロイメージングの新時代 (2017)
  • Author(s): 鹿野理子
  • Journal Title: 心身医学 Volume: 印刷中
  • NAID: 130006863502
  • Peer Reviewed
• [Journal Article] Differential activation in amygdala and plasma noradrenaline during colorectal distention by administration of corticotropin-releasing hormone between healthy individuals and patients with irritable bowel syndrome. (2016)
  • Author(s): Tanaka Y, Kanazawa M, Kano M, Morishita J, Hamaguchi T, Van Oudenhove L, Ly HG, Dupont P, Tack J, Yamaguchi T, Yanai K, Tashiro M, Fukudo S.
  • Journal Title: PLoS One Volume: 11 Issue: 7 Pages: 1-13
  • DOI: 10.1371/journal.pone.0157347
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 過敏性腸症候群における アレキシサイミア傾向の影響 (2016)
  • Author(s): 鹿野理子
  • Journal Title: 行動医学研究 Volume: 22 Pages: 65-70
  • NAID: 130006943048
  • Peer Reviewed
• [Journal Article] Associations between Single-Nucleotide Polymorphisms in Corticotropin-Releasing Hormone-Related Genes and Irritable Bowel Syndrome. (2016)
  • Author(s): Sasaki A, Sato N, Suzuki N, Kano M, Tanaka Y, Kanazawa M, Aoki M, Fukudo S.
  • Journal Title: PLoS One Volume: 11 Issue: 2 Pages: e0149322-e0149322
  • DOI: 10.1371/journal.pone.0149322
  • Peer Reviewed / Open Access
• [Journal Article] Corticotropin-Releasing Hormone Receptor 2 Gene Variants in Irritable Bowel Syndrome. (2016)
  • Author(s): Komuro H, Sato N, Sasaki A, Suzuki N, Kano M, Tanaka Y, Yamaguchi-Kabata Y, Kanazawa M, Warita H, Aoki M, Fukudo S.
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: e0147817-e0147817
  • DOI: 10.1371/journal.pone.0147817
  • Peer Reviewed / Open Access
• [Journal Article] Serotonin Transporter Gene Polymorphism Modulates Activity and Connectivity within an Emotional Arousal Network of Healthy Men during an Aversive Visceral Stimulus. (2015)
  • Author(s): Kilpatrick LA, Mayer EA, Labus JS, Gupta A, Hamaguchi T, Mizuno T, Komuro H, Kano M, Kanazawa M, Aoki M, Fukudo S.
  • Journal Title: PLoS One Volume: 10 Issue: 4 Pages: 1-15
  • DOI: 10.1371/journal.pone.0123183
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The influence of extraversion on brain activity at baseline and during the experience and expectation of visceral pain. Personality and Individual Differences. (2015)
  • Author(s): Rufflea JK, Farmer AD, Kano M, Giampietro V, Aziz Q, Coen SJ.
  • Journal Title: Personality and Individual Differences Volume: 74 Pages: 248-253
  • DOI: 10.1016/j.paid.2014.10.024
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Normal values and reproducibility of the real-time index of vagal tone in healthy humans: a multi-center study (2014)
  • Author(s): Farmer AD, Coen SJ, Kano M, Weltens N, Ly HF, Botha C, Paine PA,, Van Oudenhovec L, Aziz Q
  • Journal Title: Annals of Gastroenterology Volume: ２７ Pages: 362-368
  • Peer Reviewed
• [Journal Article] Psychophysiological responses to visceral and somatic pain in functional chest pain identify clinically relevant pain clusters (2014)
  • Author(s): Farmer AD, Coen SJ, Kano M, Naqvi H, Paine PA, Scott SM, Furlong PL, Lightman SL, Knowles CH, Aziz Q
  • Journal Title: Neurogastroenterol Motil Volume: 26(1) Issue: 1 Pages: 139-48
  • DOI: 10.1111/nmo.12245
  • Peer Reviewed
• [Journal Article] Physiological and psychological individual differences influence resting brain function measured by ASL perfusion. (2014)
  • Author(s): Kano M, Coen SJ, Farmer AD, Aziz Q, Williams SC, Alsop DC, Fukudo S, O'Gorman RL.
  • Journal Title: Brain Struct Funct Volume: 219 Issue: 5 Pages: 1673-1684
  • DOI: 10.1007/s00429-013-0593-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ABSENCE OF VISCERAL SENSITIVITY AND VAGAL TONE INTERACTION IN THE ANTERIOR CINGULATE CORTEX AND BRAINSTEM OF PATIENTS WITH IRRITABLE BOWEL SYNDROME (2018)
  • Author(s): Michiko Kano, Makoto Yoshizawa, Tomohiko Muratsubaki, Joe Morishita, Lukas Van Oudenhove, Patrick Dupont, Shin Fukudo
  • Organizer: 76th annual scientific meeting, American Psychosomatic Society
  • Int'l Joint Research
• [Presentation] 過敏性腸症候群における迷走神経活動と脳内疼痛制御機構の機能変化 (2017)
  • Author(s): 鹿野 理子、村椿 智彦、吉澤 誠、森下 城、Van Oudenhove Lukas、Dupont Patrick、福土 審
  • Organizer: 第40回日本神経科学大会
  • Place of Presentation: 幕張メッセ（千葉県、千葉市）
  • Year and Date: 2017-07-20
• [Presentation] Gene, hormone, and immunity of alexithymia (2017)
  • Author(s): Kano M, Grabe HJ, Terock J
  • Organizer: A Disorder of Emotion Regulation: Alexithymia
  • Place of Presentation: Leiden, Netherlands
  • Year and Date: 2017-05-01
  • Int'l Joint Research / Invited
• [Presentation] Brain imaging in Gastroenterology (2017)
  • Author(s): Michiko Kano
  • Organizer: the ANMA & JSNM Joint Meeting 2017
  • Place of Presentation: 大阪国際会議場（大阪府、大阪市）
  • Year and Date: 2017-03-23
  • Int'l Joint Research / Invited
• [Presentation] Resting State Functional Connectivity in Irritable Bowel Syndrome (2017)
  • Author(s): Kano M, Dupont P, Muratsubaki T, Morishita J, Ly HG,, Van Oudenhove L, Fukudo S
  • Organizer: the 75th Annual Scientific Meeting of the American Psychosomatic Society
  • Place of Presentation: Sevilla(Spain)
  • Year and Date: 2017-03-15
  • Int'l Joint Research
• [Presentation] Impaired top-down regulation to hypothalamic-pituitary-adrenal axis from the pregenual anterior cingulate cortex in patients with irritable bowel syndrome (2017)
  • Author(s): Kano M, Muratsubaki T, Morishita J, Yagihashi M, Ly HG, Dupont P, Van Oudenhove L, Kanazawa M, Fukudo S
  • Organizer: the 75th Annual Scientific Meeting of the American Psychosomatic Society
  • Place of Presentation: Sevilla(Spain)
  • Year and Date: 2017-03-15
  • Int'l Joint Research
• [Presentation] Gene and Hormone (2017)
  • Author(s): Michiko Kano, Hans Jorgen Grabe, Jan Terock
  • Organizer: A Disorder of Emotion Regulation: Alexithymia
  • Int'l Joint Research / Invited
• [Presentation] Lack of visceral sensation and vagal tone interactions in the anterior cingulate cortex and brainstem in patients with irritable bowel syndrome (2017)
  • Author(s): Michiko Kano, Makoto Yoshizawa, Tomohiko Muratsubaki, Joe Morishita, Lukas Van Oudenhove, Patrick Dupont, Shin Fukudo
  • Organizer: 第40回 日本神経科学会
  • Int'l Joint Research
• [Presentation] Dysfunction of peripheral and central corticotropin-releasing hormonal (CRH) system in patients with irritable bowel syndrome (IBS) (2016)
  • Author(s): Kano M, Muratsubaki T, Morishita J, Yagihashi M, Ly HG, Dupont P, Van Oudenhove L, Kanazawa M, Fukudo S
  • Organizer: 16th World Congress on Pain
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-09-26
  • Int'l Joint Research
• [Presentation] Association between brain activity in the mPFC during rectal distention and ACTH response in irritable bowel syndrome (2016)
  • Author(s): Kano M, Muratsubaki T, Morishita J, Yagihashi M, Ly HG, Dupont P, Van Oudenhove L, Kanazawa M, Fukudo S
  • Organizer: The 39th annual meeting of Japan neuroscience meeting
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-07-20
• [Presentation] Graph Theoretical Analysis of Resting State Functional Connectivity in Irritable Bowel Syndrome (2016)
  • Author(s): Kano M, Dupont P, Morishita J, Muratsubaki T, Ly HG, Van Oudenhove L, Fukudo S
  • Organizer: The 22th Annual Meeting of the Organization for Human Brain Mapping
  • Place of Presentation: Genova(Switzerland)
  • Year and Date: 2016-06-26
  • Int'l Joint Research
• [Presentation] 内臓痛は体性痛と異なるか？―脳活動パターン分析による比較 (2016)
  • Author(s): 鹿野理子
  • Organizer: 第57回日本心身医学会総会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-06-04
  • Invited
• [Presentation] Context of uncertainty modulates brain activity during rectal distention and non-distention in subjects with IBS (2016)
  • Author(s): Kano M, Muratsubaki T, Morishita J, Yagihashi M, Ly HG, Dupont P, Van Oudenhove L, Fukudo S.
  • Organizer: 74th Annucal Scientific Meeting of the American Psychosomatic Society
  • Place of Presentation: Denver, CO, USA
  • Year and Date: 2016-03-09
  • Int'l Joint Research
• [Presentation] Gut feelings in alexithymia (2016)
  • Author(s): Michiko Kano
  • Organizer: シンポジウム “Emotion, interoception, and the sense of agency”
  • Place of Presentation: 慶応義塾大学三田キャンパス（東京都、港区）
  • Int'l Joint Research / Invited
• [Presentation] 過敏性腸症候群（IBS）における副腎皮質刺激ホルモン（ACTH）反応性の内臓感覚脳活動への影響 (2015)
  • Author(s): 鹿野理子、村椿智彦、八木橋真央、森下城、フィンヤオ・リ、パトリック・デュポン、ルーカス・フォンオーデンフォーフ、金澤素、福土審
  • Organizer: 第17回日本神経消化器病学会
  • Place of Presentation: 恩納村（沖縄）
  • Year and Date: 2015-11-12
• [Presentation] Context of Uncertainty Modulates Brain Activity during Rectal Distension in IBS (2015)
  • Author(s): Kano M, Muratsubaki T, Morishita J, Ly HG, Dupont P, Van Oudenhove L, Fukudo S
  • Organizer: James W. Freston Conference
  • Place of Presentation: Chicago, Illinois, US
  • Year and Date: 2015-08-29
  • Int'l Joint Research
• [Presentation] Influence of alexithymia on brain activity during rectal distention in subjects with irritable bowel syndrome. (2015)
  • Author(s): Kano M, Muratsubaki T, Morishita J, Yagihashi M, Ly HG, Dupont P, Van Oudenhove L, Fukudo S.
  • Organizer: The ICPM 23rd World Congress on Psychosomatic medicine.
  • Place of Presentation: Glasgow, Scotland
  • Year and Date: 2015-08-19
  • Int'l Joint Research
• [Presentation] Brain actitivity during rectal distension associated with increased colonic response to CRH in IBS subjects. (2015)
  • Author(s): Kano M, Muratsubaki T; Yagihashi M, Morishita J, Tanaka Y, Ly HG, Dupont P, Van Oudenhove L, Kanazawa M, Fukudo S.
  • Organizer: The 38th annual meeting of Japan neuroscience meeting
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
• [Presentation] Uncertainty of Incoming Stimulus Modulates Brain Activity during Rectal Distension in IBS subjects. (2015)
  • Author(s): Kano M, Muratsubaki T, Morishita J, Ly HG, Dupont P, Van Oudenhove L, Fukudo S.
  • Organizer: The 21th Annual Meeting of the Organization for Human Brain Mapping
  • Place of Presentation: Honolulu, Hawaii, US,
  • Year and Date: 2015-06-14
  • Int'l Joint Research
• [Presentation] Alexithymia influences brain activity during rectal distention in subjects with irritable bowel syndrome (2015)
  • Author(s): Kano M, Muratsubaki T, Morishita J, Yagihashi M, Ly HG, Dupont P, Van Oudenhove L, Fukudo S.
  • Organizer: 73th Annucal Scientific Meeting of the American Psychosomatic Society
  • Place of Presentation: Savannah, GA, USA
  • Year and Date: 2015-03-19
• [Presentation] Association between Increased Colonic Response to CRH in Subjects with irritable bowel syndrome (IBS) and Insular Activity during rectal distension (2014)
  • Author(s): Kano M, Muratsubaki T; Yagihashi M, Morishita J, Tanaka Y, Ly HG, Dupont P, Van Oudenhove L, Kanazawa M, Fukudo S
  • Organizer: The First CiNet Conference: New Directions in Pain Neuroscience
  • Place of Presentation: Osaka
  • Year and Date: 2014-12-03
• [Presentation] Conditioning and Extinction Learning of Visceral Pain in Human- an fMRI Study. (2014)
  • Author(s): Kano M, Coen SJ, Farmer AD, Giampietro VP, Brammer MJ, Fukudo S, Aziz Q.
  • Organizer: The 37th annual meeting of Japan neuroscience meeting
  • Place of Presentation: Yokohama
  • Year and Date: 2014-09-12
• [Presentation] Insular activity during rectal distension associated with increased colonic response to CRH in IBS subjects (2014)
  • Author(s): Kano M, Muratsubaki T; Yagihashi M, Morishita J, Tanaka Y, Ly HG, Dupont P, Van Oudenhove L, Kanazawa M, Fukudo S
  • Organizer: 13th International Congress of Behavioral Medicine
  • Place of Presentation: Groningen, Netherlands
  • Year and Date: 2014-08-20 – 2014-08-23
  • Invited
• [Presentation] Association between Increased Colonic Response to CRH in irritable bowel syndrome (IBS) Subjects and Insular Activity during rectal distension (2014)
  • Author(s): Kano M, Muratsubaki T; Yagihashi M, Morishita J, Tanaka Y, Ly HG, Dupont P, Van Oudenhove L, Kanazawa M, Fukudo S
  • Organizer: The 20th Annual Meeting of the Organization for Human Brain Mapping
  • Place of Presentation: Hamburg, Germany
  • Year and Date: 2014-06-08 – 2014-06-12
• [Presentation] 内臓感覚の記憶と消去の脳内メカニズム－条件付け課題を用いたfMRI研究 (2014)
  • Author(s): 鹿野理子、Steven J Coen, Adam D Farmer, Vincent Gampietro, Mick Brammer, 福土審, Qasim Aziz
  • Organizer: 第55回日本心身医学会総会
  • Place of Presentation: 千葉
  • Year and Date: 2014-06-06 – 2014-06-07
• [Presentation] Increased Colonic Response to CRH in IBS Subjects Associates with Insular Activity during rectal distension. (2014)
  • Author(s): Kano M, Muratsubaki T; Yagihashi M, Morishita J, Tanaka Y, Ly HG, Dupont P, Van Oudenhove L, Kanazawa M, Fukudo S
  • Organizer: The 115th Annucal Meeting of American Gastroenterological Association
  • Place of Presentation: Chicago Ill, USA
  • Year and Date: 2014-05-04 – 2014-05-06
• [Book] 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 (2018)
  • Author(s): 鹿野理子
  • Publisher: 中外医学社