• Yaohui Zhu, Tugba Colak, Mohan Shenoy, Liansheng Liu, Reetesh Pai, Cuiping Li, Kshama Mehta, and Pankaj Jay Pasricha.
• Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
• Gastroenterology. 2011 Jul 1;141(1):370-7.

Background & AimsThe 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.MethodsCP 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.ResultsBlockade 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.ConclusionsThese 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.Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

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