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Background: Visceral hypersensitivity plays a major role in the pathophysiology of irritable bowel syndrome, as shown by balloon distension studies. 5‐HT3 receptors on afferent nerves may modulate visceral sensitivity and be the target of new treatments for irritable bowel syndrome. 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 distension with a barostat. Methods: Twenty‐five irritable bowel syndrome patients were included in a randomized double‐blind parallel group trial; data were available for 22 (Rome criteria; 48 ± 11 years; 13 men and 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 overnight fast, isobaric phasic distensions were performed (4 mmHg steps, 5 min) up to the step triggering a sensation of abdominal pain. Results: Groups were comparable at inclusion (age, sex, symptoms, bowel habits). There were no differences between treatment groups in pressure recorded within the bag at the time of first sensation of abdominal pain. However, bag volumes were significantly increased. At the first sensation threshold, median volume differences of 61 mL and 90 mL (P = 0.028) were recorded with alosetron 0.25 mg b.d. and 4 mg b.d., respectively. At the threshold of abdominal pain, these differences were 71 mL (P = 0.039) and 84 mL (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 to 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 thereby contribute to changes in perception of colonic distension and improvement in the symptoms of irritable bowel syndrome.

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Despite considerable progress in the knowledge of human colonic motor function, the relationships between electrical and mechanical activity, their significance in regard to transit of digesta, and their temporal daily distribution in health and disease remain uncertain.' Previous attempts to evaluate electrical activity of the colon in man have allowed the identification of two distinct slow-wave rhythms with frequencies of 9-12 and 2-5-3.5 c/min respectively2-4 and, in one report, spike potentials were found to be superimposed on the higher slow-wave rhythm.2 Whereas the low frequency slow wave has the same incidence and frequency along the whole colon, the higher frequency slow wave has a greater incidence in the right colon, although its frequency is higher in the left colon.5 Lack of further information has been due to the technical difficulty of attaching clip or suction electrodes to the proximal colon. Failure to achieve adequate records of spiking activity was also due to the use of long time constants