Lipid‐induced colonic hypersensitivity in irritable bowel syndrome: the role of 5‐HT₃ receptors

Abstract

SUMMARYBackground: Irritable bowel syndrome patients demonstrate colonic hypersensitivity after duodenal lipid infusion. Aim: To investigate the role of 5-hydroxytryptamine-3 (5-HT 3 ) receptors in this sensory component of the gastrocolonic response in irritable bowel syndrome. Methods: Fifteen female patients with diarrhoea-predominant irritable bowel syndrome completed a trial with the 5-HT 3 receptor antagonist alosetron (1 mg b.d.) or placebo (b.d.) over 15 days, followed by the alternative treatment. Each treatment period was followed by a colonic distension trial before and after duodenal lipids. Changes in colonic thresholds, tone and compliance and viscerosomatic referral pattern after lipids were compared between treatments.

The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome

“…Similar findings were previously reported with l -NMMA, an inhibitor of nitric oxide synthase, where the threshold for discomfort was only increased in patients with IBS with visceral hypersensitivity but not in healthy volunteers 20. The degree of improvement observed in our study is comparable to previous studies evaluating other drugs such as l -NMMA,20 alosetron21 and fedotozine,22 of which alosetron has proved to be clinically efficient in patients with IBS 23…”

Serotonergic and non‐serotonergic targets in the pharmacotherapy of visceral hypersensitivity

“…In the stomach, however, 5‐HT 3 receptor antagonists were found to leave the viscoelastic properties unchanged, 139–140 although ondansetron could reduce nausea and gastric sensitivity to distension during intraduodenal lipid infusion in healthy subjects 141 . In women with IBS whose predominant symptom was diarrhoea (IBS‐D), alosetron reduced colonic hypersensitivity induced by duodenal lipids 142 …”

Pharmacology of serotonin: what a clinician should know

“…79 In female patients with diarrhoea predominant IBS, alosetron reduced colonic hypersensitivity induced by duodenal lipids. 80 The hypothesis that 5-HT 3 receptors may modulate perception of visceral sensations by acting at the central level has also been explored. Mayer et al carried out a randomised placebo controlled functional brain imaging study 81 to assess the effect of alosetron (1-4 mg twice daily for three weeks) on IBS symptoms, regional brain activation by rectosigmoid distension, and associated perceptual and emotional responses.…”