Tegaserod,a 5-HT4 receptor partial agonist,decreases sensitivity to rectal distension in healthy subjects

BACKGROUND: Tegaserod reduces the symptoms associated with irritable bowel syndrome, and anti-nociceptive effects have been demonstrated in animals. Its effect on the rectal sensitivity in humans has not been delineated clearly. AIM: To evaluate the action of tegaserod on rectal sensitivity in response to distension by means of a reflexological technique based on electrophysiological recordings of the RIII nociceptive reflex. METHODS: A randomized, double-blind, placebo-controlled study, performed in 20 healthy women, quantified the effects of slow or rapid rectal distensions on the RIII reflex at baseline and on day 8 following treatment with either placebo or tegaserod (6 mg b.d.). RESULTS: At baseline, slow distensions performed up to the pain threshold induced gradual inhibitions of the RIII reflex. On day 8, these inhibitory effects were significantly reduced in the tegaserod group, but not in the placebo group (P = 0.0001). The effects of rapid distensions were not significantly modified by tegaserod or placebo. The intensity of subjective pain perception and rectal compliance were not altered by either treatment. CONCLUSION: These results suggest that tegaserod reduces the sensitivity to rectal distension in healthy subjects and interacts with the processing of sensory visceral information.