Intraluminal acid induces oesophageal shortening via capsaicin-sensitive neurokinin neurons

Paterson, William G.; Miller, David V.; Dilworth, Neil; Assini, Joseph B.; Lourenssen, Sandra; Blennerhassett, Michael G.
October 2007
Gut;Oct2007, Vol. 56 Issue 10, p1347
Academic Journal
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 degrariulating 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 MEN 10376. Compound 48/80 induced sustained contraction of LSM strips in a concentration- dependent fashion and this was associated with evidence of mast cell degranulatiori. The 48/80-induced ISM 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 capsaiciri-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.


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