Nerve growth factor modulates TRPV1 expression and function and mediates pain in chronic pancreatitis

Yaohui Zhu, Tugba Colak, Mohan Shenoy, Liansheng Liu, Reetesh Pai, Cuiping Li, Kshama Mehta, Pankaj Jay Pasricha

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)370-377
Number of pages8
JournalGastroenterology
Volume141
Issue number1
DOIs
StatePublished - Jul 2011
Externally publishedYes

Keywords

  • Chronic Pancreatitis
  • Nerve Growth Factor
  • Pain
  • TRPV1

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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