Influence of GABA-B Agonist Baclofen on Capsaicin-Induced Excitation of Secondary Peristalsis in Humans

Overview

Journal Clin Transl Gastroenterol

Specialty Gastroenterology

Date 2017 Oct 6

PMID 28981081

Citations 2

Authors

Wei-Yi Lei

Jui-Sheng Hung

Tso-Tsai Liu

Chih-Hsun Yi

Chien-Lin Chen

Affiliations

Soon will be listed here.

Abstract

Objectives: Esophageal instillation of capsaicin enhances secondary peristalsis, but the γ-aminobutyric acid receptor type B (GABA-B) agonist baclofen inhibits secondary peristalsis. This study aimed to investigate whether baclofen could influence heartburn perception and secondary peristalsis subsequent to capsaicin infusion in healthy adults.

Methods: Secondary peristalsis was performed by slow and rapid mid-esophagus air injections in 15 healthy subjects. Two different sessions including esophageal infusion of capsaicin-containing red pepper sauce (0.84 mg) following pre-treatment with placebo or baclofen were randomly performed to test the effects on heartburn perception and secondary peristalsis.

Results: The intensity of heartburn symptom subsequent to capsaicin infusion was significantly greater after pre-treatment of baclofen as compared with the placebo (P=0.03). Baclofen significantly increased the threshold volume of secondary peristalsis to slow air injections subsequent to esophageal capsaicin infusion (P<0.001). Baclofen significantly increased the threshold volume of secondary peristalsis to rapid air injections subsequent to esophageal capsaicin infusion (P<0.01). The frequency of secondary peristalsis subsequent to capsaicin infusion was significantly decreased with baclofen as compared with the placebo (P<0.002). Baclofen had no effect on any of the peristaltic parameters of secondary peristalsis subsequent to capsaicin infusion.

Conclusions: The GABA-B agonist baclofen appears to attenuate the esophagus to capsaicin-induced excitation of secondary peristalsis in healthy adults. Our study suggests the inhibitory modulation for GABA-B receptors on capsaicin-sensitive afferents mediating secondary peristalsis in human esophagus.

Citing Articles

New Developments in the Diagnosis and Management of Gastroesophageal Reflux.

Jiang Y, Clarke J Curr Treat Options Gastroenterol. 2020; 18(1):69-81.

PMID: 32072470 DOI: 10.1007/s11938-020-00275-1.

Baclofen and gastroesophageal reflux disease: seeing the forest through the trees.

Clarke J, Fernandez-Becker N, Regalia K, Triadafilopoulos G Clin Transl Gastroenterol. 2018; 9(3):137.

PMID: 29599487 PMC: 5876385. DOI: 10.1038/s41424-018-0010-y.

References

Brooks P, Glaum S, Miller R, Spyer K . The actions of baclofen on neurones and synaptic transmission in the nucleus tractus solitarii of the rat in vitro. J Physiol. 1992; 457:115-29. PMC: 1175720. DOI: 10.1113/jphysiol.1992.sp019367. View

Sifrim D, Zerbib F . Diagnosis and management of patients with reflux symptoms refractory to proton pump inhibitors. Gut. 2012; 61(9):1340-54. DOI: 10.1136/gutjnl-2011-301897. View

Chen C, Liu T, Yi C, Orr W . Effects of capsaicin-containing red pepper sauce suspension on esophageal secondary peristalsis in humans. Neurogastroenterol Motil. 2010; 22(11):1177-82, e312-3. DOI: 10.1111/j.1365-2982.2010.01561.x. View

Janssens J, Valembois P, VANTRAPPEN G, Hellemans J, Pelemans W . Is the primary peristaltic contraction of the canine esophagus bolus-dependent?. Gastroenterology. 1973; 65(5):750-6. View

Bolser D, Aziz S, DeGennaro F, Kreutner W, Egan R, Siegel M . Antitussive effects of GABAB agonists in the cat and guinea-pig. Br J Pharmacol. 1993; 110(1):491-5. PMC: 2175970. DOI: 10.1111/j.1476-5381.1993.tb13837.x. View

Helm J, Dodds W, Pelc L, Palmer D, Hogan W, Teeter B . Effect of esophageal emptying and saliva on clearance of acid from the esophagus. N Engl J Med. 1984; 310(5):284-8. DOI: 10.1056/NEJM198402023100503. View

Lehmann A, Antonsson M, Flardh M, Karrberg L . Activation of the GABA(B) receptor inhibits transient lower esophageal sphincter relaxations in dogs. Gastroenterology. 1999; 117(5):1147-54. DOI: 10.1016/s0016-5085(99)70400-2. View

Schoeman M, Holloway R . Stimulation and characteristics of secondary oesophageal peristalsis in normal subjects. Gut. 1994; 35(2):152-8. PMC: 1374487. DOI: 10.1136/gut.35.2.152. View

Tominaga M, Caterina M, Malmberg A, Rosen T, Gilbert H, Skinner K . The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron. 1998; 21(3):531-43. DOI: 10.1016/s0896-6273(00)80564-4. View

10.

Bowery N, Pratt G . GABAB receptors as targets for drug action. Arzneimittelforschung. 1992; 42(2A):215-23. View

11.

Janssens J, Valembois P, Hellemans J, VANTRAPPEN G, Pelemans W . Studies on the necessity of a bolus for the progression of secondary peristalsis in the canine esophagus. Gastroenterology. 1974; 67(2):245-51. View

12.

Koek G, Sifrim D, Lerut T, Janssens J, Tack J . Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-oesophageal reflux refractory to proton pump inhibitors. Gut. 2003; 52(10):1397-402. PMC: 1773817. DOI: 10.1136/gut.52.10.1397. View

13.

Page A, Blackshaw L . GABA(B) receptors inhibit mechanosensitivity of primary afferent endings. J Neurosci. 1999; 19(19):8597-602. PMC: 6783028. View

14.

Capaday C . The effects of baclofen on the stretch reflex parameters of the cat. Exp Brain Res. 1995; 104(2):287-96. DOI: 10.1007/BF00242014. View

15.

Hanack C, Moroni M, Lima W, Wende H, Kirchner M, Adelfinger L . GABA blocks pathological but not acute TRPV1 pain signals. Cell. 2015; 160(4):759-770. DOI: 10.1016/j.cell.2015.01.022. View

16.

Minocha A, Galligan J . Excitatory and inhibitory responses mediated by GABAA and GABAB receptors in guinea pig distal colon. Eur J Pharmacol. 1993; 230(2):187-93. DOI: 10.1016/0014-2999(93)90801-n. View

17.

Sifrim D, Janssens J . Secondary peristaltic contractions, like primary peristalsis, are preceded by inhibition in the human esophageal body. Digestion. 1996; 57(1):73-8. DOI: 10.1159/000201316. View

18.

Pandolfino J, Shi G, Zhang Q, Kahrilas P . Absence of a deglutitive inhibition equivalent with secondary peristalsis. Am J Physiol Gastrointest Liver Physiol. 2004; 288(4):G671-6. DOI: 10.1152/ajpgi.00388.2004. View

19.

Schoeman M, Holloway R . Secondary oesophageal peristalsis in patients with non-obstructive dysphagia. Gut. 1994; 35(11):1523-8. PMC: 1375605. DOI: 10.1136/gut.35.11.1523. View

20.

Zhang Q, Lehmann A, Rigda R, Dent J, Holloway R . Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease. Gut. 2002; 50(1):19-24. PMC: 1773078. DOI: 10.1136/gut.50.1.19. View