title: 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.
abstract: Irritable bowel syndrome (IBS) often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis, but it is not clear how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS patients compared to healthy controls. Brain H215O- positron emission tomography (PET) was performed in 16 male IBS patients and 16 age-matched male controls during baseline, no distention, mild and intense distention of the colorectum using barostat bag inflation. Either CRH (2 μg/kg) or saline (1:1) was then injected intravenously and the same distention protocol was repeated. Plasma adrenocorticotropic hormone (ACTH), serum cortisol and plasma noradrenaline levels were measured at each stimulation. At baseline, CRH without colorectal distention induced more activation in the right amygdala in IBS patients than in controls. During intense distention after CRH injection, controls showed significantly greater activation than IBS patients in the right amygdala. Plasma ACTH and serum cortisol secretion showed a significant interaction between drug (CRH, saline) and distention. Plasma noradrenaline at baseline significantly increased after CRH injection compared to before injection in IBS. Further, plasma noradrenaline showed a significant group (IBS, controls) by drug by distention interaction. Exogenous CRH differentially sensitizes brain regions of the emotional-arousal circuitry within the visceral pain matrix to colorectal distention and synergetic activation of noradrenergic function in IBS patients and healthy individuals.
authors.affiliation: Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.|Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Motoyori
authors.initials: M
authors.lastname: Kanazawa
authors.affiliation: Department of Frontier Research Institute for Interdisciplinary Sciences, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kano
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Joe
authors.initials: J
authors.lastname: Morishita
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Toyohiro
authors.initials: T
authors.lastname: Hamaguchi
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical & Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Lukas
authors.initials: L
authors.lastname: Van Oudenhove
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical & Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Huynh Giao
authors.initials: HG
authors.lastname: Ly
authors.affiliation: Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dupont
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Clinical & Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
authors.affiliation: Departments of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Departments of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan.|Departments of Cyclotron RI Center, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
authors.affiliation: Departments of Cyclotron RI Center, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Fukudo
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D016022:Case-Control Studies; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000502:physiology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000378:metabolism* / Q000473:pathology / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D049268:Positron-Emission Tomography; D059265:Visceral Pain / Q000209:etiology / Q000523:psychology; D055815:Young Adult
chemical_list: D003346:Corticotropin-Releasing Hormone; D009638:Norepinephrine