PT  - JOURNAL ARTICLE
AU  - William G Paterson
AU  - David V Miller
AU  - Neil Dilworth
AU  - Joseph B Assini
AU  - Sandra Lourenssen
AU  - Michael G Blennerhassett
TI  - Intraluminal acid induces oesophageal shortening via capsaicin-sensitive neurokinin neurons
AID  - 10.1136/gut.2006.115881
DP  - 2007 Oct 01
TA  - Gut
PG  - 1347--1352
VI  - 56
IP  - 10
4099  - http://gut.bmj.com/content/56/10/1347.short
4100  - http://gut.bmj.com/content/56/10/1347.full
SO  - Gut2007 Oct 01; 56
AB  - Objective: Intraluminal acid evokes reflex contraction of oesophageal longitudinal smooth muscle (LSM) and consequent oesophageal shortening. This reflex may play a role in the pathophysiology of oesophageal pain syndromes and hiatus hernia formation. The aim of the current study was to elucidate further the mechanisms of acid-induced oesophageal shortening. Design: Intraluminal acid perfusion of the intact opossum smooth muscle oesophagus was performed in vitro in the presence and absence of neural blockade and pharmacological antagonism of the neurokinin 2 receptor, while continuously recording changes in oesophageal axial length. In addition, the effect of these antagonists on the contractile response of LSM strips to the mast cell degranulating agent 48/80 was determined. Finally, immunohistochemistry was performed to look for evidence of LSM innervation by substance P/calcitonin gene-related peptide (CGRP)-containing axons. Results: Intraluminal acid perfusion induced longitudinal axis shortening that was completely abolished by capsaicin desensitization, substance P desensitization, or the application of the neurokinin 2 receptor antagonist MEN10376. Compound 48/80 induced sustained contraction of LSM strips in a concentration-dependent fashion and this was associated with evidence of mast cell degranulation. The 48/80-induced LSM contraction was antagonized by capsaicin desensitization, substance P desensitization and MEN10376, but not tetrodotoxin. Immunohistochemistry revealed numerous substance P/CGRP-containing neurons innervating the LSM and within the mucosa. Conclusions: This study suggests that luminal acid activates a reflex pathway involving mast cell degranulation, activation of capsaicin-sensitive afferent neurons and the release of substance P or a related neurokinin, which evokes sustained contraction of the oesophageal LSM. This pathway may be a target for treatment of oesophageal pain syndromes.