The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health. Issue 3 (6th December 2020)

• Record Type: Journal Article
• Authors: Broers, Charlotte; Geeraerts, Annelies; Boecxstaens, Veerle; Van Houtte, Brecht; Geysen, Hannelore; Peersman, Nele; Vermeersch, Pieter; Vanuytsel, Tim; Tack, Jan; Pauwels, Ans
• Is Part Of: Neurogastroenterology & motility. Volume 33:Issue 3(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-06
• Subjects: buspirone -- citalopram -- electric stimulation -- esophagus -- healthy volunteers -- hot temperature -- pain -- physical stimulation -- physiopathology -- serotonin; Gastrointestinal system -- Motility -- Periodicals; Gastrointestinal system -- Innervation -- Periodicals; 616.33
• DOI: 10.1111/nmo.14057
• Languages: English
• ISSNs: 1350-1925

Abstract

Abstract: Background: Esophageal hypersensitivity is considered an important pathophysiological mechanism in refractory gastroesophageal reflux disease (GERD) patients. Serotonin (5‐HT) plays an important role in the regulation of GI (gastrointestinal) secretion, motility and sensitivity. Previous studies found that altered 5‐HT availability has no clear effects on esophageal/GI sensations. Our aim was therefore to investigate the role of 5‐HT in esophageal sensitivity in healthy volunteers (HV). Methods: Esophageal sensitivity to thermal, mechanical, electrical, and chemical stimuli was assessed in 3 different placebo‐controlled studies. In the first study, the effect of citalopram (40 mg; 5‐HT reuptake inhibitor; intravenous) was investigated ( n = 14). In the second study, the effect of buspirone (20 mg; 5HT1A agonist; oral) was investigated ( n = 10). In the third study, acute tryptophan depletion (ATD) was used to decrease 5‐HT levels to investigate the effect of reduced 5‐HT availability on esophageal sensitivity ( n = 15). Key Results: No difference was observed in esophageal sensitivity after the administration of citalopram or buspirone (all p > 0.06). In contrast, pain perception threshold to chemical stimulation was increased after ATD ( p = 0.017, Cohen's d+ = 0.67). No effect was found on the first perception or pain tolerance threshold. ATD had no influence on esophageal sensitivity to thermal, mechanical, and electrical stimulation compared with placebo. Conclusions and Inferences: ATD, which induces 5‐HT depletion, significantly decreased pain perception threshold during chemical stimulation, without affecting sensitivity to mechanical, thermal, or electrical stimulation. These findings confirm the involvement of 5‐HT in the control of esophageal acid sensitivity, but identifying the receptors involved requires more ligands and studies. Abstract : Results of esophageal chemical stimulation after ATD or in the control condition. A significant decrease in PPT was seen after ATD compared to control. ATD, which induces 5‐HT depletion, significantly decreased pain perception threshold during chemical stimulation, without affecting sensitivity to mechanical, thermal or electrical stimulation. These findings confirm involvement of 5‐HT in the control of esophageal acid sensitivity, but identifying the receptors involved requires more ligands and studies. ATD, acute tryptophan depletion; PPT, pain perception threshold; PTT, pain tolerance threshold. * p < 0.05, corrected for multiple testing.