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A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis.

Publication ,  Journal Article
Noble, MD; Romac, J; Vigna, SR; Liddle, RA
Published in: Gut
November 2008

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has a high risk of pancreatitis although the underlying mechanisms are unclear. Transient receptor potential vanilloid 1 (TRPV1) is a cation channel expressed on C and Adelta fibres of primary sensory neurons and is activated by low pH. TRPV1 activation causes release of inflammatory mediators that produce oedema and neutrophil infiltration. We previously demonstrated that neurogenic factors contribute to the pathogenesis of pancreatitis. Resiniferatoxin (RTX) is a TRPV1 agonist that, in high doses, defunctionalises C and Adelta fibres. When we discovered that the pH of radio-opaque contrast solutions used for ERCP was 6.9, we hypothesised that low pH may contribute to the development of contrast-induced pancreatitis via activation of TRPV1. METHODS: Rats underwent equal pressure pancreatic ductal injection of contrast solutions at varying pH with or without RTX. RESULTS: Contrast solution (pH 6.9) injected into the pancreatic duct caused a significant increase in pancreatic oedema, serum amylase, neutrophil infiltration, and histological damage. Solutions of pH 7.3 injected at equal pressure caused little damage. The severity of the pancreatitis was significantly increased by injection of solutions at pH 6.0. To determine if the effects of low pH were mediated by TRPV1, RTX was added to the contrast solutions. At pH levels of 6.0 and 6.9, RTX significantly reduced the severity of pancreatitis. CONCLUSIONS: Contrast solutions with low pH contribute to the development of pancreatitis through a TRPV1-dependent mechanism. It is possible that increasing the pH of contrast solution and/or adding an agent that inhibits primary sensory nerve activation may reduce the risk of post-ERCP pancreatitis.

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Published In

Gut

DOI

EISSN

1468-3288

Publication Date

November 2008

Volume

57

Issue

11

Start / End Page

1566 / 1571

Location

England

Related Subject Headings

  • TRPV Cation Channels
  • Severity of Illness Index
  • Rats, Sprague-Dawley
  • Rats
  • Pancreatitis
  • Pancreas
  • Neurons, Afferent
  • Neurogenic Inflammation
  • Male
  • Hydrogen-Ion Concentration
 

Citation

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Noble, M. D., Romac, J., Vigna, S. R., & Liddle, R. A. (2008). A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis. Gut, 57(11), 1566–1571. https://doi.org/10.1136/gut.2008.148551
Noble, M. D., J. Romac, S. R. Vigna, and R. A. Liddle. “A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis.Gut 57, no. 11 (November 2008): 1566–71. https://doi.org/10.1136/gut.2008.148551.
Noble MD, Romac J, Vigna SR, Liddle RA. A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis. Gut. 2008 Nov;57(11):1566–71.
Noble, M. D., et al. “A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis.Gut, vol. 57, no. 11, Nov. 2008, pp. 1566–71. Pubmed, doi:10.1136/gut.2008.148551.
Noble MD, Romac J, Vigna SR, Liddle RA. A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis. Gut. 2008 Nov;57(11):1566–1571.

Published In

Gut

DOI

EISSN

1468-3288

Publication Date

November 2008

Volume

57

Issue

11

Start / End Page

1566 / 1571

Location

England

Related Subject Headings

  • TRPV Cation Channels
  • Severity of Illness Index
  • Rats, Sprague-Dawley
  • Rats
  • Pancreatitis
  • Pancreas
  • Neurons, Afferent
  • Neurogenic Inflammation
  • Male
  • Hydrogen-Ion Concentration