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Substance P and calcitonin gene related peptide mediate pain in chronic pancreatitis and their expression is driven by nerve growth factor.
JOP. 2011 Jul 08; 12(4):389-94.JOP

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 up-regulation 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 gene-related 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 gene-related 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.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21737902

Citation

Liu, LianSheng, et al. "Substance P and Calcitonin Gene Related Peptide Mediate Pain in Chronic Pancreatitis and Their Expression Is Driven By Nerve Growth Factor." JOP : Journal of the Pancreas, vol. 12, no. 4, 2011, pp. 389-94.
Liu L, Shenoy M, Pasricha PJ. Substance P and calcitonin gene related peptide mediate pain in chronic pancreatitis and their expression is driven by nerve growth factor. JOP. 2011;12(4):389-94.
Liu, L., Shenoy, M., & Pasricha, P. J. (2011). Substance P and calcitonin gene related peptide mediate pain in chronic pancreatitis and their expression is driven by nerve growth factor. JOP : Journal of the Pancreas, 12(4), 389-94.
Liu L, Shenoy M, Pasricha PJ. Substance P and Calcitonin Gene Related Peptide Mediate Pain in Chronic Pancreatitis and Their Expression Is Driven By Nerve Growth Factor. JOP. 2011 Jul 8;12(4):389-94. PubMed PMID: 21737902.
* Article titles in AMA citation format should be in sentence-case
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,LianSheng, AU - Shenoy,Mohan, AU - Pasricha,Pankaj Jay, Y1 - 2011/07/08/ PY - 2011/7/9/entrez PY - 2011/7/9/pubmed PY - 2011/12/16/medline SP - 389 EP - 94 JF - JOP : Journal of the pancreas JO - JOP VL - 12 IS - 4 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 up-regulation 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 gene-related 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 gene-related 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. SN - 1590-8577 UR - https://www.unboundmedicine.com/medline/citation/21737902/Substance_P_and_calcitonin_gene_related_peptide_mediate_pain_in_chronic_pancreatitis_and_their_expression_is_driven_by_nerve_growth_factor_ L2 - http://www.serena.unina.it/index.php/jop/article/view/3226/3426 DB - PRIME DP - Unbound Medicine ER -