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Sensory Nerves pp 227-257 | Cite as

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

  • Amanda J. Page
  • L. Ashley BlackshawEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series (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.

Keywords

Visceral pain Vagal afferents Gastro-oesophageal reflux Lower oesophageal sphincter 

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

Notes

Acknowledgement

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

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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 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 SciencesUniversity of AdelaideAdelaideAustralia

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