Modification of Visceral Sensitivity and Pain in Irritable Bowel Syndrome by 5-HT₃ Antagonism (Ondansetron)

Abstract

Intrinsic neurons containing serotonin (5-HT) are involved in the regulation of gastrointestinal motor function and are also thought to be important in the modulation of visceral sensory function. We have evaluated the effect of a specific 5-HT3 antagonist (ondansetron, O) on visceral sensation and rectal compliance in a randomized, double-blind, cross-over, placebo (P) controlled study of·16 mg 3 times/day, in healthy volunteers and patients with irritable bowel syndrome (IBS). Symptoms were also evaluated in the latter group. A 2-week run-in period was 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 diary, and physiological tests of anal manometry, rectal sensory testing to distension and electrical stimulation, and rectal compliance. Ten healthy subjects completed the entire study, and 6 IBS patients completed the diary card evaluation, including 5 who also completed the physiological evaluation.·caused significantly (p < 0.01) firmer stools when considering both subject groups together. In the healthy subjects no physiological parameters were altered by O. In IBS patients the rectal sensory threshold to electrical stimulation tended to increase with·(20 vs. 28 mA, P vs. O, median, p = 0.06) while the urge (80 vs. 60 ml, p = 0.05) and maximum tolerated volumes (130 vs. 90, p = 0.03) to distension tended to decrease with O. Patients with IBS experienced significantly fewer daily episodes of pain while on·(2 vs. 1, p = 0.03). Serotonin-3 antagonism (O) causes firmer bowel actions in all subjects, and may affect gut sensitivity and pain in patients with IBS.

Effects of Tropisetron, a 5-HT₃ Receptor Antagonist, on Proximal Gastric Motor and Sensory Function in Nonulcer Dyspepsia

“…Like in NUD patients, the benefit of 5-HT 3 receptor antagonists has not been evaluated in large clinical trials in patients with irritable bowel syndrome. The results of studies with small patient numbers are conflicting, but of course some reports show promising results [13, 25, 26]. …”

Update in the Therapeutic Management of Irritable Bowel Syndrome

“…A doubleblind pilot study with ondansetron (a 5-HT 3 -specific blocker) versus placebo in 14 patients with diarrhea-predominant IBS revealed no significant differences in terms of colonic transit modification between both groups, although there were 11 dropouts in this study [31]. Another double-blind study performed in 1996 with ondansetron versus placebo proved a significant decrease in abdominal distension and the frequency of abdominal pain compared with placebo [32]. Maxton et al [33] performed a similar placebo-controlled trial with ondansetron including 50 patients and demonstrated a significant reduction in the frequency of bowel movements and an increase in stool consistency in those with diarrhea-predominant IBS [33].…”

The clinical potential of ramosetron in the treatment of irritable bowel syndrome with diarrhea (IBS-D)

“…Benefit was apparent for both agents, in patients of either sex. An old 5-HT 3 receptor antagonist widely used as an antiemetic, ondansetron, has showed benefits in patients with IBS in small trials [Steadman et al 1992;Goldberg et al 1996]. Recently, a large RCT of 120 patients with IBS-D showed that ondansetron of 4 mg for 5 weeks improves stool consistency, reduced urgency, frequency, and bloating, but does not reduce abdominal pain [Garsed et al 2014].…”