Substance P and calcitonin gene related peptide mediate pain in chronic pancreatitis and their expression is driven by nerve growth factor

Research output: Contribution to journalArticle

Abstract

Context Calcitonin gene-related peptide (CGRP), substance P and nerve growth factor play an important role in inflammatory pain in various somatic pain models but their role in chronic pancreatitis has not been well studied. Objectives The aim of this study was to investigate the effects of intrathecal administration of calcitonin gene-related peptide antagonist and substance P receptor antagonist on pain behavior in a rat model of chronic pancreatitis and to determine whether nerve growth factor drives the upregulation of expression of these neuropeptides in sensory neurons. Methods Pancreatitis was induced by retrograde infusion of trinitobenzene sulfonic acid into the pancreatic duct of adult rats. Three weeks post infusion continuous intrathecal infusion of the calcitonin gene-related peptide antagonist alpha CGRP8-37 or neurokinin-1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 was administered for seven days. The effects of treatment on pancreatic hyperalgesia were assessed by sensitivity of the abdominal wall to von Frey filament probing as well as by the nocifensive response to electrical stimulation of the pancreas. In a separate experiment chronic pancreatitis was induced and pancreas specific dorsal root ganglion neurons labeled with DiI were assessed for calcitonin gene-related peptide and substance P immunoreactivity. Results Intrathecal infusion of calcitonin generelated peptide and neurokinin-1 receptor antagonists significantly attenuated behavioral pain responses in rats with chronic pancreatitis. Further, treatment of chronic pancreatitis rats with nerve growth factor antibody significantly reduced pancreas specific neurons expressing calcitonin gene-related peptide and substance P in thoracic dorsal root ganglion. Conclusions Calcitonin generelated peptide and substance P mediate pancreatic hyperalgesia in chronic pancreatitis and nerve growth factor in turn sustains the up-regulation of these neuropeptides in pancreatic sensory neurons.

Original languageEnglish (US)
Pages (from-to)389-394
Number of pages6
JournalJournal of the Pancreas
Volume12
Issue number4
StatePublished - Jul 2011
Externally publishedYes

Fingerprint

Calcitonin Gene-Related Peptide
Chronic Pancreatitis
Nerve Growth Factor
Substance P
Neurokinin-1 Receptor Antagonists
Pain
Pancreas
Hyperalgesia
Calcitonin
Spinal Ganglia
Sensory Receptor Cells
Neuropeptides
Up-Regulation
Nociceptive Pain
Neurons
Sulfonic Acids
Pancreatic Ducts
Abdominal Wall
Pancreatitis
Electric Stimulation

Keywords

  • Calcitonin Gene-Related Peptide
  • Chronic
  • Nerve Growth Factor
  • Pancreatitis
  • Rats
  • Substance P

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Hepatology

Cite this

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title = "Substance P and calcitonin gene related peptide mediate pain in chronic pancreatitis and their expression is driven by nerve growth factor",
abstract = "Context Calcitonin gene-related peptide (CGRP), substance P and nerve growth factor play an important role in inflammatory pain in various somatic pain models but their role in chronic pancreatitis has not been well studied. Objectives The aim of this study was to investigate the effects of intrathecal administration of calcitonin gene-related peptide antagonist and substance P receptor antagonist on pain behavior in a rat model of chronic pancreatitis and to determine whether nerve growth factor drives the upregulation of expression of these neuropeptides in sensory neurons. Methods Pancreatitis was induced by retrograde infusion of trinitobenzene sulfonic acid into the pancreatic duct of adult rats. Three weeks post infusion continuous intrathecal infusion of the calcitonin gene-related peptide antagonist alpha CGRP8-37 or neurokinin-1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 was administered for seven days. The effects of treatment on pancreatic hyperalgesia were assessed by sensitivity of the abdominal wall to von Frey filament probing as well as by the nocifensive response to electrical stimulation of the pancreas. In a separate experiment chronic pancreatitis was induced and pancreas specific dorsal root ganglion neurons labeled with DiI were assessed for calcitonin gene-related peptide and substance P immunoreactivity. Results Intrathecal infusion of calcitonin generelated peptide and neurokinin-1 receptor antagonists significantly attenuated behavioral pain responses in rats with chronic pancreatitis. Further, treatment of chronic pancreatitis rats with nerve growth factor antibody significantly reduced pancreas specific neurons expressing calcitonin gene-related peptide and substance P in thoracic dorsal root ganglion. Conclusions Calcitonin generelated peptide and substance P mediate pancreatic hyperalgesia in chronic pancreatitis and nerve growth factor in turn sustains the up-regulation of these neuropeptides in pancreatic sensory neurons.",
keywords = "Calcitonin Gene-Related Peptide, Chronic, Nerve Growth Factor, Pancreatitis, Rats, Substance P",
author = "Liu, {Lian Sheng} and Mohan Shenoy and Pasricha, {Pankaj Jay}",
year = "2011",
month = "7",
language = "English (US)",
volume = "12",
pages = "389--394",
journal = "Journal of the Pancreas",
issn = "1590-8577",
publisher = "E.S. Burioni Ricerche Bibliografiche",
number = "4",

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TY - JOUR

T1 - Substance P and calcitonin gene related peptide mediate pain in chronic pancreatitis and their expression is driven by nerve growth factor

AU - Liu, Lian Sheng

AU - Shenoy, Mohan

AU - Pasricha, Pankaj Jay

PY - 2011/7

Y1 - 2011/7

N2 - Context Calcitonin gene-related peptide (CGRP), substance P and nerve growth factor play an important role in inflammatory pain in various somatic pain models but their role in chronic pancreatitis has not been well studied. Objectives The aim of this study was to investigate the effects of intrathecal administration of calcitonin gene-related peptide antagonist and substance P receptor antagonist on pain behavior in a rat model of chronic pancreatitis and to determine whether nerve growth factor drives the upregulation of expression of these neuropeptides in sensory neurons. Methods Pancreatitis was induced by retrograde infusion of trinitobenzene sulfonic acid into the pancreatic duct of adult rats. Three weeks post infusion continuous intrathecal infusion of the calcitonin gene-related peptide antagonist alpha CGRP8-37 or neurokinin-1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 was administered for seven days. The effects of treatment on pancreatic hyperalgesia were assessed by sensitivity of the abdominal wall to von Frey filament probing as well as by the nocifensive response to electrical stimulation of the pancreas. In a separate experiment chronic pancreatitis was induced and pancreas specific dorsal root ganglion neurons labeled with DiI were assessed for calcitonin gene-related peptide and substance P immunoreactivity. Results Intrathecal infusion of calcitonin generelated peptide and neurokinin-1 receptor antagonists significantly attenuated behavioral pain responses in rats with chronic pancreatitis. Further, treatment of chronic pancreatitis rats with nerve growth factor antibody significantly reduced pancreas specific neurons expressing calcitonin gene-related peptide and substance P in thoracic dorsal root ganglion. Conclusions Calcitonin generelated peptide and substance P mediate pancreatic hyperalgesia in chronic pancreatitis and nerve growth factor in turn sustains the up-regulation of these neuropeptides in pancreatic sensory neurons.

AB - Context Calcitonin gene-related peptide (CGRP), substance P and nerve growth factor play an important role in inflammatory pain in various somatic pain models but their role in chronic pancreatitis has not been well studied. Objectives The aim of this study was to investigate the effects of intrathecal administration of calcitonin gene-related peptide antagonist and substance P receptor antagonist on pain behavior in a rat model of chronic pancreatitis and to determine whether nerve growth factor drives the upregulation of expression of these neuropeptides in sensory neurons. Methods Pancreatitis was induced by retrograde infusion of trinitobenzene sulfonic acid into the pancreatic duct of adult rats. Three weeks post infusion continuous intrathecal infusion of the calcitonin gene-related peptide antagonist alpha CGRP8-37 or neurokinin-1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 was administered for seven days. The effects of treatment on pancreatic hyperalgesia were assessed by sensitivity of the abdominal wall to von Frey filament probing as well as by the nocifensive response to electrical stimulation of the pancreas. In a separate experiment chronic pancreatitis was induced and pancreas specific dorsal root ganglion neurons labeled with DiI were assessed for calcitonin gene-related peptide and substance P immunoreactivity. Results Intrathecal infusion of calcitonin generelated peptide and neurokinin-1 receptor antagonists significantly attenuated behavioral pain responses in rats with chronic pancreatitis. Further, treatment of chronic pancreatitis rats with nerve growth factor antibody significantly reduced pancreas specific neurons expressing calcitonin gene-related peptide and substance P in thoracic dorsal root ganglion. Conclusions Calcitonin generelated peptide and substance P mediate pancreatic hyperalgesia in chronic pancreatitis and nerve growth factor in turn sustains the up-regulation of these neuropeptides in pancreatic sensory neurons.

KW - Calcitonin Gene-Related Peptide

KW - Chronic

KW - Nerve Growth Factor

KW - Pancreatitis

KW - Rats

KW - Substance P

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JO - Journal of the Pancreas

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