title: Nerve growth factor modulates TRPV1 expression and function and mediates pain in chronic pancreatitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Tugba
authors.initials: T
authors.lastname: Colak
authors.forename: Mohan
authors.initials: M
authors.lastname: Shenoy
authors.forename: Liansheng
authors.initials: L
authors.lastname: Liu
authors.forename: Reetesh
authors.initials: R
authors.lastname: Pai
authors.forename: Cuiping
authors.initials: C
authors.lastname: Li
authors.forename: Kshama
authors.initials: K
authors.lastname: Mehta
authors.forename: Pankaj Jay
authors.initials: PJ
authors.lastname: Pasricha
mesh_terms: D000700:Analgesics / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D004195:Disease Models, Animal; D015536:Down-Regulation; D006930:Hyperalgesia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008564:Membrane Potentials; D020932:Nerve Growth Factor / Q000276:immunology / Q000378:metabolism*; D010146:Pain / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D017288:Pain Threshold; D010179:Pancreas / Q000294:innervation*; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000700:Analgesics; D000906:Antibodies; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014302:Trinitrobenzenesulfonic Acid; D020932:Nerve Growth Factor