title: Brain-derived neurotrophic factor is upregulated in rats with chronic pancreatitis and mediates pain behavior.
abstract: OBJECTIVE
  We examined the role of brain-derived neurotrophic factor (BDNF) in the pathogenesis of pain in an experimental model of chronic pancreatitis (CP).
  
  
  METHODS
  Pancreatitis was induced by retrograde infusion of trinitrobenzene sulfonic acid into the pancreatic duct of adult rats. Twenty-one days after injection, BDNF expression was examined in pancreas-specific dorsal root ganglia (DRGs) by immunohistochemistry, and protein levels were quantified from DRGs and spinal cord extracts. The effects of intrathecal infusion of a neutralizing antibody to BDNF on pancreatic hyperalgesia were assessed by the sensitivity of the abdominal wall to filament probing as well as the nocifensive behavior to electrical stimulation of the pancreas.
  
  
  RESULTS
  Levels of BDNF in DRGs and spinal cords (T9-13) were significantly higher in trinitrobenzene sulfonic acid rats compared with controls, accompanied by an increase in the number of pancreas-specific neurons expressing BDNF immunoreactivity. Brain-derived neurotrophic factor antagonism suppressed phospho-tropomyosin-related kinase B receptor levels in the spinal cord and significantly reduced behavioral responses in rats with CP.
  
  
  CONCLUSIONS
  Brain-derived neurotrophic factor is upregulated in pancreas-specific primary afferent neurons in rats with CP, and BDNF antagonism is associated with a reduction of pain-related behavior in these animals, suggesting an important role for this neurotransmitter in the nociception of CP.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hughes
authors.forename: Mohan
authors.initials: M
authors.lastname: Shenoy
authors.forename: Liansheng
authors.initials: L
authors.lastname: Liu
authors.forename: Tugba
authors.initials: T
authors.lastname: Colak
authors.forename: Kshama
authors.initials: K
authors.lastname: Mehta
authors.forename: Pankaj J
authors.initials: PJ
authors.lastname: Pasricha
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000503:physiopathology* / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D014302:Trinitrobenzenesulfonic Acid; D020813:Receptor, trkB