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Local disruption of the celiac ganglion inhibits substance P release and ameliorates caerulein-induced pancreatitis in rats.

Publication ,  Journal Article
Noble, MD; Romac, J; Wang, Y; Hsu, J; Humphrey, JE; Liddle, RA
Published in: Am J Physiol Gastrointest Liver Physiol
July 2006

Primary sensory neurons of the C and Adelta subtypes express the vanilloid capsaicin receptor TRPV1 and contain proinflammatory peptides such as substance P (SP) that mediate neurogenic inflammation. Pancreatic injury stimulates these neurons causing the release of SP in the pancreas resulting in pancreatic edema and neutrophil infiltration that contributes to pancreatitis. Axons of primary sensory neurons innervating the pancreas course through the celiac ganglion. We hypothesized that disruption of the celiac ganglion by surgical excision or inhibition of C and Adelta fibers through blockade of TRPV1 would reduce the severity of experimental pancreatitis by inhibiting neurogenic inflammation. Resiniferatoxin (RTX) is a specific TRPV1 agonist that, in high doses, selectively destroys C and Adelta fibers. Sprague-Dawley rats underwent surgical ganglionectomy or application of 10 microg RTX (vs. vehicle alone) to the celiac ganglion. One week later, pancreatitis was induced by six hourly intraperitoneal injections of caerulein (50 microg/kg). The severity of pancreatitis was assessed by serum amylase, pancreatic edema, and pancreatic myeloperoxidase (MPO) activity. SP receptor (neurokinin-1 receptor, NK-1R) internalization in acinar cells, used as an index of endogenous SP release, was assessed by immunocytochemical quantification of NK-1R endocytosis. Caerulein administration caused significant increases in pancreatic edema, serum amylase, MPO activity, and NK-1R internalization. RTX treatment and ganglionectomy significantly reduced pancreatic edema by 46% (P < 0.001) and NK-1R internalization by 80% and 51% (P < 0.001 and P < 0.05, respectively). RTX administration also significantly reduced MPO activity by 47% (P < 0.05). Neither treatment affected serum amylase, consistent with a direct effect of caerulein. These results demonstrate that disruption of or local application of RTX to the celiac ganglion inhibits SP release in the pancreas and reduces the severity of acute secretagogue-induced pancreatitis. It is possible that selectively disrupting TRPV1-bearing neurons could be used to reduce pancreatitis severity.

Duke Scholars

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

ISSN

0193-1857

Publication Date

July 2006

Volume

291

Issue

1

Start / End Page

G128 / G134

Location

United States

Related Subject Headings

  • Substance P
  • Rats, Sprague-Dawley
  • Rats
  • Pancreatitis
  • Pancreas
  • Male
  • Gastroenterology & Hepatology
  • Ganglia, Sympathetic
  • Denervation
  • Ceruletide
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Noble, M. D., Romac, J., Wang, Y., Hsu, J., Humphrey, J. E., & Liddle, R. A. (2006). Local disruption of the celiac ganglion inhibits substance P release and ameliorates caerulein-induced pancreatitis in rats. Am J Physiol Gastrointest Liver Physiol, 291(1), G128–G134. https://doi.org/10.1152/ajpgi.00442.2005
Noble, Marc D., Joelle Romac, Yu Wang, Jay Hsu, John E. Humphrey, and Rodger A. Liddle. “Local disruption of the celiac ganglion inhibits substance P release and ameliorates caerulein-induced pancreatitis in rats.Am J Physiol Gastrointest Liver Physiol 291, no. 1 (July 2006): G128–34. https://doi.org/10.1152/ajpgi.00442.2005.
Noble MD, Romac J, Wang Y, Hsu J, Humphrey JE, Liddle RA. Local disruption of the celiac ganglion inhibits substance P release and ameliorates caerulein-induced pancreatitis in rats. Am J Physiol Gastrointest Liver Physiol. 2006 Jul;291(1):G128–34.
Noble, Marc D., et al. “Local disruption of the celiac ganglion inhibits substance P release and ameliorates caerulein-induced pancreatitis in rats.Am J Physiol Gastrointest Liver Physiol, vol. 291, no. 1, July 2006, pp. G128–34. Pubmed, doi:10.1152/ajpgi.00442.2005.
Noble MD, Romac J, Wang Y, Hsu J, Humphrey JE, Liddle RA. Local disruption of the celiac ganglion inhibits substance P release and ameliorates caerulein-induced pancreatitis in rats. Am J Physiol Gastrointest Liver Physiol. 2006 Jul;291(1):G128–G134.

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

ISSN

0193-1857

Publication Date

July 2006

Volume

291

Issue

1

Start / End Page

G128 / G134

Location

United States

Related Subject Headings

  • Substance P
  • Rats, Sprague-Dawley
  • Rats
  • Pancreatitis
  • Pancreas
  • Male
  • Gastroenterology & Hepatology
  • Ganglia, Sympathetic
  • Denervation
  • Ceruletide