Modulation of esophageal afferent pathways by 5-HT<inf>3</inf> receptor inhibition

Abstract

Background The study aims were to investigate whether neural pathways involving 5-HT3 receptors mediate: (i) distension-induced upper esophageal sphincter (UES) relaxation reflex, (ii) esophageal sensitivity to acid and electrical stimuli, and (iii) viserosomatic sensitization following acid exposure. Methods In Study I, in a double-blind crossover trial (n=9) esophageal sensory and pain thresholds to electrical stimulation were measured in the esophagus, midsternum, and the foot, before subjects were randomized to receive either Ondansetron (8mg i.v.) or NaCl (0.9% w/v). HCl (0.15mol L-1) was then infused into distal esophagus and electrical thresholds were reassessed. Following electrical sensory threshold testing, subjects received a second esophageal infusion of HCl to evaluate esophageal sensitivity to acid. In Study II (N=10), frequencies of distension-induced UES relaxation responses were scored before and after treatment with Ondansetron and NaCl in a double-blind crossover trial. Key Results In Study I, ondansetron had no effect on esophageal sensitivity to HCl or acid-induced sensitization. However, blockade of 5-HT3 receptors did reduce midsternum somatic pain thresholds. Sixty minutes after esophageal acid exposure, pain thresholds were significantly lower in the ondansetron arm (mean Δ-1.36±0.4mA) when compared with NaCl (mean Δ-0.14±0.58mA) (P<0.05). In Study II, 5-HT3 receptor blockade had no significant effect on UES relaxation reflex. Conclusions & Inferences This study does not support the hypothesis that in health, 5-HT3 receptors play a significant role in esophago-UES distention-induced relaxation reflex and esophageal sensitivity to acid or electrical stimulation. It does provide new evidence for involvement of 5-HT3 receptors in viscerosomatic sensitization. © 2013 Blackwell Publishing Ltd.