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Roles of Gastro-oesophageal Afferents in the Mechanisms and Symptoms of Reflux Disease

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Sensory Nerves

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 194))

Abstract

Oesophageal pain is one of the most common reasons for physician consultation and/or seeking medication. It is most often caused by acid reflux from the stomach, but can also result from contractions of the oesophageal muscle. Different forms of pain are evoked by oesophageal acid, including heartburn and non-cardiac chest pain, but the basic mechanisms and pathways by which these are generated remain to be elucidated. Both vagal and spinal afferent pathways are implicated by basic research. The sensitivity of afferent fibres within these pathways may become altered after acid-induced inflammation and damage, but the severity of symptoms in humans does not necessarily correlate with the degree of inflammation. Gastro-oesophageal reflux disease (GORD) is caused by transient relaxations of the lower oesophageal sphincter, which are triggered by activation of gastric vagal mechanoreceptors. Vagal afferents are therefore an emerging therapeutic target for GORD. Pain in the absence of excess acid reflux remains a major challenge for treatment.

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Abbreviations

AMPA:

α-Amino-3-hydroxy-5-methylisoxazoleproprionate

(2R,4R)-APDC:

(2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate

ATP:

Adenosine triphosphate

CCK:

Cholecystokinin

CGRP:

Calcitonin gene-related peptide

CNQX:

(6-cyano-7-nitroquinoxaline-2,3-dione)

DHPG:

(RS)-3,5-Dihydroxyphenylglycine

GABA:

γ-Aminobutyric acid

GORD:

Gastro-oesophageal reflux disease

5-HT:

5-Hydroxytryptamine

IGLE:

Intraganglionic laminar endings

iGluR:

Ionotropic glutamate receptor

IMA:

Intramuscular array

L-AP4:

L-(+)-2-Amino-4-phosphonobutyric acid

L-NAME:

NG-nitro-L-arginine methyl ester

α,β-meATP:

α,β-Methylene ATP

mGluR:

Metabotropic glutamate receptor

MPEP:

2-Methyl-6-(phenylethynyl)pyridine

MTEP:

3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine

NCCP:

Non-cardiac chest pain

NMDA:

N-Methyl d-aspartate

TLOSR:

Transient lower oesophageal sphincter relaxation

TRPV1:

Transient receptor potential vanilloid receptor 1

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Acknowledgement

L.A.B. is supported by a National Health and Medical Research Council of Australia Senior Research fellowship.

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  1. Nerve Gut Research Laboratory, Level 1 Hanson Institute, Frome Road, Royal Adelaide Hospital, Discipline of Medicine and Discipline of Physiology, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA, 5000, Australia

    Amanda J. Page & L. Ashley Blackshaw

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  2. L. Ashley Blackshaw
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Correspondence to L. Ashley Blackshaw .

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  1. Dept. Medicine, Johns Hopkins Asthma & Allergy Center, Hopkins Bayview Circle 5501, Baltimore, 21224, U.S.A.

    Brendan J. Canning

  2. School of Biomedical & Health Sciences, King's College London, Guy's Campus, London, SE1 9RT, United Kingdom

    Domenico Spina

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Page, A.J., Blackshaw, L.A. (2009). Roles of Gastro-oesophageal Afferents in the Mechanisms and Symptoms of Reflux Disease. In: Canning, B., Spina, D. (eds) Sensory Nerves. Handbook of Experimental Pharmacology, vol 194. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-79090-7_7

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