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Nerve growth factor modulates TRPV1 expression and function and mediates pain in chronic pancreatitis.Gastroenterology. 2011 Jul; 141(1):370-7.G
Abstract
BACKGROUND & AIMS
The pathogenesis of pain in chronic pancreatitis (CP) is poorly understood and treatment remains difficult. We hypothesized that nerve growth factor (NGF) plays a key role in this process via its effects on the transient receptor potential vanilloid 1, TRPV1.
METHODS
CP was induced by intraductal injection of trinitrobenzene sulfonic acid in rats. After 3 weeks, anti-NGF antibody or control serum was administered daily for 1 week. Pancreatic hyperalgesia was assessed by nocifensive behavioral response to electrical stimulation of the pancreas as well as by referred somatic pain assessed by von Frey filament testing. TRPV1 currents in pancreatic sensory neurons were examined by patch-clamp. The expression and function of TRPV1 in pancreas-specific nociceptors was examined by immunostaining and quantification of messenger RNA levels.
RESULTS
Blockade of NGF significantly attenuated pancreatic hyperalgesia and referred somatic pain compared with controls. It also decreased TRPV1 current density and open probability and reduced the proportion of pancreatic sensory neurons that expressed TRPV1 as well as levels of TRPV1 in these neurons.
CONCLUSIONS
These findings emphasize a key role for NGF in pancreatic pain and highlight the role it plays in the modulation of TRPV1 expression and activity in CP.
Links
MeSH
AnalgesicsAnalysis of VarianceAnimalsAntibodiesDisease Models, AnimalDown-RegulationHyperalgesiaMaleMembrane PotentialsNerve Growth FactorPainPain ThresholdPancreasPancreatitis, ChronicPatch-Clamp TechniquesRNA, MessengerRatsRats, Sprague-DawleySensory Receptor CellsSignal TransductionTRPV Cation ChannelsTime FactorsTrinitrobenzenesulfonic Acid
Pub Type(s)
Journal Article
Research Support, N.I.H., Extramural
Language
eng
PubMed ID
21473865