Molecular and behavioral changes in nociception in a novel rat model of chronic pancreatitis for the study of pain

John H. Winston, Zhi Jun He, Mohan Shenoy, Shu Yuan Xiao, Pankaj Jay Pasricha

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

The approach to the management of painful chronic pancreatitis has been empirical, primarily due to the lack of information about biological mechanisms producing pain. To facilitate research into pain mechanisms, our aim was to assess a rat model of chronic pancreatitis induced by pancreatic infusion of trinitrobenzene sulfonic acid as a model of painful pancreatitis. Nociception was assessed by measuring mechanical sensitivity of the abdomen and by recording the number of nocifensive behaviors in response to electrical stimulation of the pancreas. Expression of neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) in the thoracic dorsal root ganglia receiving input from the pancreas and nerve growth factor (NGF) in the pancreas were measured. Rats with pancreatitis exhibited marked increase in sensitivity to mechanical probing of the abdomen and increased sensitivity to noxious electrical stimulation of the pancreas. There were significant increases in NGF protein in the pancreas and in expression of neuropeptides CGRP and SP in the sensory neurons from dorsal root ganglia receiving input from the pancreas. We have established quantitative measures of referred nociception and pancreatic hyperalgesia in a rat model of chronic pancreatitis that bears histological similarities to the human disease. This model has considerable construct, face and predictive validity for the human condition. It is of importance for the study of the pathogenesis of pain in this condition and can facilitate the development of new therapeutic options.

Original languageEnglish (US)
Pages (from-to)214-222
Number of pages9
JournalPain
Volume117
Issue number1-2
DOIs
StatePublished - Sep 1 2005

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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