The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health.
Adult
Buspirone
/ pharmacology
Citalopram
/ pharmacology
Esophagus
/ drug effects
Female
Gastroesophageal Reflux
/ physiopathology
Healthy Volunteers
Humans
Male
Middle Aged
Pain Threshold
Physical Stimulation
Proof of Concept Study
Sensory Thresholds
Serotonin
/ physiology
Serotonin Receptor Agonists
/ pharmacology
Selective Serotonin Reuptake Inhibitors
/ pharmacology
Tryptophan
/ deficiency
Young Adult
buspirone
citalopram
electric stimulation
esophagus
healthy volunteers
hot temperature
pain
physical stimulation
physiopathology
serotonin
Journal
Neurogastroenterology and motility
ISSN: 1365-2982
Titre abrégé: Neurogastroenterol Motil
Pays: England
ID NLM: 9432572
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
22
05
2020
revised:
22
10
2020
accepted:
17
11
2020
pubmed:
7
12
2020
medline:
1
12
2021
entrez:
6
12
2020
Statut:
ppublish
Résumé
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). 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). 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. 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.
Sections du résumé
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.
Substances chimiques
Serotonin Receptor Agonists
0
Serotonin Uptake Inhibitors
0
Citalopram
0DHU5B8D6V
Serotonin
333DO1RDJY
Tryptophan
8DUH1N11BX
Buspirone
TK65WKS8HL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14057Informations de copyright
© 2020 John Wiley & Sons Ltd.
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