Article Text

other Versions

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


              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

              Statistics from

              Request Permissions

              If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

              Linked Articles

              • Digest
                Robin Spiller Emad M El-Omar