IRRITABLE BOWEL SYNDROME

Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome

Y Sagami¹, Y Shimada², J Tayama², T Nomura¹, M Satake¹, Y Endo¹, T Shoji¹, K Karahashi¹, M Hongo³, S Fukudo²

¹ Department of Psychosomatic Medicine, Tohoku University School of Medicine, Sendai, Japan
² Department of Behavioural Medicine, Tohoku University School of Medicine, Sendai, Japan
³ Department of Comprehensive Medicine, Tohoku University School of Medicine, Sendai, Japan

Correspondence to:
Correspondence to:
Professor S Fukudo
Department of Behavioural Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba, Sendai, 980-8575, Japan; sfukudo{at}mail.tains.tohoku.ac.jp

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 -helical CRH (hCRH), 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 hCRH (10 µg/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 hCRH. Administration of hCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. hCRH 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 hCRH.

Conclusion: Peripheral administration of hCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.

Abbreviations: IBS, irritable bowel syndrome; CRH, corticotropin releasing hormone; hCRH, -helical CRH; ES, electrical stimulation; ACTH, adrenocorticotropic hormone; ENS, enteric nervous system

Keywords: irritable bowel syndrome; corticotropin releasing hormone; -helical corticotropin releasing hormone; colonic motor function; colonic hyperalgesia

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