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Intraluminal acid induces oesophageal shortening via capsaicin-sensitive neurokinin neurons
  1. William G Paterson (patersow{at}hdh.kari.net)
  1. Queen's University, Canada
    1. David V Miller (dvm{at}post.queensu.ca)
    1. Queen's University, Canada
      1. Neil Dilworth (neildilworth{at}hotmail.com)
      1. Queen's University, Canada
        1. Joseph B Assini (joeassini{at}hotmail.com)
        1. Queen's University, Canada
          1. Sandra Lourenssen (slour{at}meds.queensu.ca)
          1. Queen's University, Canada
            1. Michael G Blennerhassett (mblen{at}meds.queensu.ca)
            1. Queen's University, Canada

              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.

              • oesophagitis
              • reflux
              • smooth muscle
              • tachykinins

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