Intraluminal acid induces oesophageal shortening via capsaicin-sensitive neurokinin neurons

William G Paterson ^1*, David V Miller ¹, Neil Dilworth ¹, Joseph B Assini ¹, Sandra Lourenssen ¹ and Michael G Blennerhassett ¹

¹ Queen's University, Canada

^* To whom correspondence should be addressed. E-mail: patersow{at}hdh.kari.net.

Accepted 4 May 2007

Abstract

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 further elucidate 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 (NK)-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/CGRP-containing axons.

Results: Intraluminal acid perfusion induced longitudinal axis shortening that was completely abolished by capsaicin desensitization, substance P desensitization, or application of the NK-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 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.

Keywords: oesophagitis, reflux, smooth muscle, tachykinins

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