EFFECT OF ALOSETRON ON RESPONSES TO COLONIC DISTENSION IN PATIENTS WITH IRRITABLE-BOWEL-SYNDROME

Background: Visceral hypersensitivity plays a major role in the pathop hysiology of irritable bowel syndrome, as shown by balloon distension studies. 5-HT3 receptors on afferent nerves may modulate visceral sens itivity and be the target of new treatments for irritable bowel syndro me. Aim: To evaluate the effects of alosetron, a potent and selective 5-HT3 antagonist, on the perception of colonic distension by patients with irritable bowel syndrome, and on the colonic compliance to disten sion with a barostat. Methods: Twenty-five irritable bowel syndrome pa tients were included in a randomized double-blind parallel group trial ; data were available for 22 (Rome criteria; 48 +/- 11 years: 13 men a nd nine women). Patients were treated for 7 days with placebo (n = 6), alosetron 0.25 mg b.d, (n = 8) or alosetron 4 mg b.d. (n = 8). On day 6, a barostat bag was placed in the left colon. On day 7, after an ov ernight fast, isobaric phasic distensions were performed (4 mmHg steps , 5 min) up to the step triggering a sensation of abdominal pain. Resu lts: Groups were comparable at inclusion (age, sex, symptoms, bowel ha bits). There were no differences between treatment groups in pressure recorded within the bag at the time of first sensation of abdominal pa in, However, bag volumes were significantly increased. At the first se nsation threshold, median volume differences of 61 mt and 90 mt (P = 0 .028) were recorded with alosetron 0.25 mg b.d. and 4 mg b.d., respect ively. At the threshold of abdominal pain, these differences were 71 m t (P = 0.039) and 84 mt (P = 0.017). Colonic compliance increased from 5.9 mL/mmHg on placebo to 7.6 mL/mmHg on alosetron 0.25 mg b.d. and t o 9.8 mL/mmHg (P = 0.034) on alosetron 4 mg b.d. Conclusion: Alosetron increases the compliance of the colon to distension, and could thereb y contribute to changes in perception of colonic distension and improv ement in the symptoms of irritable bowel syndrome.