MODIFICATION OF VISCERAL SENSITIVITY AND PAIN IN IRRITABLE-BOWEL-SYNDROME BY 5-HT3 ANTAGONISM (ONDANSETRON)

Intrinsic neurons containing serotonin (5-HT) are involved in the regu lation of gastrointestinal motor function and are also thought to be i mportant in the modulation of visceral sensory function. We have evalu ated the effect of a specific 5-HT3 antagonist (ondansetron, O) on vis ceral sensation and rectal compliance in a randomized, double-blind, c ross-over, placebo (P) controlled study of O 16 mg 3 times/day, in hea lthy volunteers and patients with irritable bowel syndrome (IBS). Symp toms were also evaluated in the latter group. A 2-week run-in period w as followed by two 2-week treatment arms of P and O, separated by a 2- week wash-out period. Twelve healthy subjects and 9 patients with IBS were recruited. Assessment was by daily symptom and bowel function dia ry, and physiological tests of anal manometry, rectal sensory testing to distension and electrical stimulation, and rectal compliance. Ten h ealthy subjects completed the entire study, and 6 IBS patients complet ed the diary card evaluation, including 5 who also completed the physi ological evaluation. O caused significantly (p < 0.01) firmer stools w hen considering both subject groups together. In the healthy subjects no physiological parameters were altered by O. In IBS patients the rec tal sensory threshold to electrical stimulation tended to increase wit h O (20 vs. 28 mA, P vs. O, median, p = 0.06) while the urge (80 vs. 6 0 ml, p = 0.05) and maximum tolerated volumes (130 vs. 90, p = 0.03) t o distension tended to decrease with O. Patients with IBS experienced significantly fewer daily episodes of pain while on O (2 vs. 1, p = 0. 03). Serotonin-3 antagonism (O) causes firmer bowel actions in all sub jects, and may affect gut sensitivity and pain in patients with IBS.