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Intraluminal acid induces oesophageal shortening via capsaicin-sensitive neurokinin neurons
  1. William G Paterson,
  2. David V Miller,
  3. Neil Dilworth,
  4. Joseph B Assini,
  5. Sandra Lourenssen,
  6. Michael G Blennerhassett
  1. Gastrointestinal Diseases Research Unit and Departments of Medicine, Biology and Physiology, Queen’s University, Kingston, Ontario, Canada
  1. Correspondence to:
    Dr William G Paterson
    GI Division, Hotel Dieu Hospital, 166 Brock Street, Kingston, Ontario, Canada, K7L-5G2; patersow{at}hdh.kari.net

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 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.

  • CGRP, Calcitonin gene-related peptide
  • CSM, circular smooth muscle
  • EFS, electrical field stimulation
  • LSM, longitudinal smooth muscle
  • PBS, phosphate-buffered saline

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Footnotes

  • Published Online First 24 May 2007

  • Funding: Canadian Institutes of Health Research grant MOP-9978

  • Conflict of interest: None declared.

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