Background-Corticotropin-releasing hormone (CRH) plays a key role in modulating intestinal motility in stressed animals. Aims-To evaluate the eVect of CRH on intestinal motility in humans and to determine whether patients with irritable bowel syndrome (IBS) have an exaggerated response to CRH. Subjects-Ten IBS patients diagnosed by Rome criteria and 10 healthy controls. Methods-CRH (2 µg/kg) was intravenously administered during duodenal and colonic manometry and plasma adrenocorticotropic hormone (ACTH) was measured by radioimmunoassay. Results-CRH induced motility of the descending colon in both groups (p<0.001) and induced greater motility indexes in IBS patients than in controls (p<0.05). CRH produced duodenal phase III motor activity in 80% of the subjects and duodenal dysmotility in 40% of IBS patients. Abdominal symptoms evoked by CRH in IBS patients lasted significantly longer than those in controls (p<0.05). CRH induced significant increases in plasma ACTH levels in both groups (p<0.001) and produced significantly higher plasma ACTH levels in IBS patients than in controls (p<0.001). Conclusion-Human intestinal motility is probably modulated by exogenous CRH. The brain-gut in IBS patients may have an exaggerated response to CRH. (Gut 1998;42:845-849) Keywords: irritable bowel syndrome; corticotropin releasing factor; adrenocorticotropic hormone; colonic motility; duodenal motility Stress can alter gastrointestinal function but the mechamism of the stress induced intestinal response is still obscure.1 The detail of the brain-gut interaction is one of the most important factors of stress induced intestinal response and irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link. 2 We have reported that psychological stress induces colonic segmental contractions and irregular contractile activity (phase II) of the duodenal migrating motor complex (MMC) in humans and that these responses are exaggerated in IBS patients. Wrap restraint stress in rats is also reported to facilitate colonic motility and to inhibit small intestinal motility.5 6 These phenomena in rats are mimicked by intracerebroventricular [6][7][8][9] or intravenous 9 administration of corticotropin releasing hormone (CRH) and are blocked by the CRH antagonist, helical CRH 9-41 . 6-9Stress induces anxiogenic behaviour in rats and intracerebroventricular administration of CRH mimics the behavioural changes under stress. 10Furthermore, intravenous administration of CRH decreases slow wave sleep in humans. 11These findings led us to hypothesise that CRH plays a major role in the stress response of humans, both normal subjects and IBS patients. The purpose of this study was to determine whether intravenous administration of CRH aVects human gastrointestinal motility and whether CRH discriminates physiological responses in normal control subjects from those in IBS patients. Methods SUBJECTSTen normal healthy volunteers and 10 IBS patients were studied. Both groups consisted of five men and five women. Ages (controls...

Background and aims: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of a-helical CRH (ahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. Methods: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of ahCRH (10 mg/kg). Results: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of ahCRH. Administration of ahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. ahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by ahCRH. Conclusion: Peripheral administration of ahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.

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Repetitive distention of the distal sigmoid colon below the sensory threshold induced orad exaggerated motility of the colon in IBS patients. The distention inhibited motility of the small intestine in healthy subjects, but this inhibition was blunted in IBS patients. These results suggest that IBS patients may have not only visceral hypersensitivity, but also an abnormal intestinal reflex.