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The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health
Author(s) -
Broers Charlotte,
Geeraerts Annelies,
Boecxstaens Veerle,
Van Houtte Brecht,
Geysen Hannelore,
Peersman Nele,
Vermeersch Pieter,
Vanuytsel Tim,
Tack Jan,
Pauwels Ans
Publication year - 2021
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.14057
Subject(s) - stimulation , placebo , citalopram , medicine , buspirone , serotonin , agonist , gastroenterology , anesthesia , pharmacology , receptor , pathology , alternative medicine
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.