title: Nerve growth factor and its high-affinity receptor in chronic pancreatitis.
abstract: OBJECTIVE
  To study the mechanisms that are involved in nerve growth and contribute to pain generation in chronic pancreatitis (CP).
  
  
  BACKGROUND
  Chronic pancreatitis is a painful disease associated with characteristic nerve changes, including an increase in nerve number and diameter. The mechanisms that influence nerve growth are not known. Nerve growth factor (NGF) and its high-affinity tyrosine kinase receptor A (TrkA) are involved in neural development and survival and growth of central and peripheral nerves.
  
  
  METHODS
  Nerve growth factor and TrkA were investigated by Northern blot analysis, in situ hybridization, and immunohistochemical staining in the pancreases of 24 patients with CP, and the findings were correlated with clinical parameters.
  
  
  RESULTS
  By Northern blot analysis, NGF and TrkA mRNA expression were increased in 42% (13.1-fold) and 54% (5.5-fold) of the CP samples (p < 0.01), respectively. In situ hybridization revealed that in CP, enhanced NGF mRNA expression was present in metaplastic ductal cells, in degenerating acinar cells, and in acinar cells dedifferentiating into tubular structures. TrkA mRNA was intensely present in the perineurium. Further, enhanced NGF and TrkA mRNA signals were also present in intrapancreatic ganglia cells in CP samples. Immunohistochemistry confirmed the in situ hybridization findings. Analysis of the molecular findings with clinical parameters revealed a significant relation (p < 0.05) between NGF mRNA levels and pancreatic fibrosis (r = 0.64) and acinar cell damage (r = 0.74) and between TrkA mRNA and pain intensity (r = 0.84).
  
  
  CONCLUSIONS
  Activation of the NGF/TrkA pathway occurs in CP. It might influence neural morphologic changes and the pain syndrome in this disorder.
authors.affiliation: Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Friess
authors.forename: Z W
authors.initials: ZW
authors.lastname: Zhu
authors.forename: F F
authors.initials: FF
authors.lastname: di Mola
authors.forename: C
authors.initials: C
authors.lastname: Kulli
authors.forename: H U
authors.initials: HU
authors.lastname: Graber
authors.forename: A
authors.initials: A
authors.lastname: Andren-Sandberg
authors.forename: A
authors.initials: A
authors.lastname: Zimmermann
authors.forename: M
authors.initials: M
authors.lastname: Korc
authors.forename: M
authors.initials: M
authors.lastname: Reinshagen
authors.forename: M W
authors.initials: MW
authors.lastname: Büchler
mesh_terms: D000328:Adult; D015152:Blotting, Northern; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D010146:Pain / Q000209:etiology; D010179:Pancreas / Q000737:chemistry; D010195:Pancreatitis / Q000150:complications / Q000209:etiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020917:Receptor, trkA / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D020932:Nerve Growth Factor; D020917:Receptor, trkA