Role of Corticotropin-releasing Hormone in Pathophysiology of Irritable Bowel Syndrome(Symposium : Frontiers Research and Practice in Psychosomatic Medicine)

Abstract

Irritable bowel syndrome (IBS) is representative disorder to which biopsychosocial model is well adapted. In Rome III critera, IBS is defined by recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated with 2 or more of the following : improvement with defecation, onset associated with a change in frequency of stool, and/or onset associated with a change in form (appearance) of stool. Pathophysiology of IBS is characterized by gastrointestinal dysmotility, visceral hypersensitivity, and psychological abnormality. Initially these three factors were considered to be independent but gradually the mutual relationship among them was clarified. This relationship has been conceptualized as brain-gut interactions. Typical manifestation of brain-gut interactions is brain imaging during visceral perception. Corticotropin-releasing hormone (CRH) is a plausible candidate of regulating brain-gut interactions in IBS patients. We showed that peripheral administration of CRH aggravated visceral sensorimotor function as well as adrenocorticotropic hormone (ACTH) response in IBS patients. We then administered alpha-helical CRH (ahCRH), a non-selective CRH receptor antagonist to IBS patients and found improvement of colonic hypermotility, abdominal pain, anxiety, and decreased power of alpha wave in electroencephalogram induced by visceral stimulation. Activation of CRH-R1 causes colonic hypermotility, whereas stimulation of CRH-R2 inhibits gastric emptying. CRH likely plays an important role in pathophysiology of IBS.