EFFECT OF A 5HT(3)-ANTAGONIST (ONDANSETRON) ON RECTAL SENSITIVITY ANDCOMPLIANCE IN HEALTH AND THE IRRITABLE-BOWEL-SYNDROME

In some patients with the irritable bowel syndrome, rectal urgency and discomfort are major clinical problems and, under experimental condit ions, these symptoms are perceived at lesser volumes of rectal distens ion than they are in asymptomatic controls. Further, a 5-hydroxytrypta mine type-3 receptor antagonist increased the threshold for rectal dis comfort; in irritable bowel syndrome. Our aims were, (a) to measure re ctal sensation during isobaric distensions of the rectum, and (b) to t est the effect of another selective 5HT(3)-antagonist, ondansetron 0.1 5 mg/kg, on rectal sensitivity, colonic tone, rectal tone and manometr ic responses. Ten healthy volunteers and five patients with diarrhoea- predominant irritable bowel syndrome were studied. A multilumen barost atmanometric assembly was placed in the descending colon, and a second barostat balloon was positioned in the rectum. Tone in the wall of th e colon and rectum was measured by the barostat balloon volume during a constant pressure clamp, while intraluminal pressures were recorded by manometry; perceived sensations were also recorded before and after the intravenous administration of ondansetron or placebo in blinded f ashion. Rectal resistance to stretch was greater and rectal urgency wa s induced by lower distending pressures in irritable bowel syndrome, h owever, basal tone in the rectum was similar in health and irritable b owel syndrome. Ondansetron did not change rectal sensitivity (first se nsation or urgency) or tone. Rectal distension did not alter tone in t he descending colon or colonic manometry; ondansetron did not influenc e any index of colonic function. We conclude that in diarrhoea-predomi nant irritable bowel syndrome there is reduced rectal compliance and t he rectum is abnormally sensitive to a pressure stimulus, but this is not altered by 5HT(3)-blockade with ondansetron at the dose used.