title: Association between gallstone-evoked pain, inflammation and proliferation of nerves in the gallbladder: a possible explanation for clinical differences.
abstract: OBJECTIVE
  To investigate whether enhanced neuroproliferation could be involved in the pathogenesis of gallstone pain.
  
  
  METHODS
  Gallbladders from 117 patients with gallstones and 43 controls were examined. The gallbladder samples were immunostained against the pan-neuronal marker PGP 9.5 and the number of nerves and nerve area per tissue area estimated.
  
  
  RESULTS
  More nerves and an increased nerve area per tissue area were found in uncomplicated symptomatic gallstone disease. In comparison, acute cholecystitis displayed a significantly (p=0.01) decreased number of nerves and nerve area per tissue area. In both categories, the gallbladder neck contained more nerves (p=0.06 and 0.04, respectively) and an increased nerve area per tissue area (p=0.034 and 0.008, respectively) than the body.
  
  
  CONCLUSIONS
  Uncomplicated disease showed enhanced neuroproliferation, significantly more in the gallbladder neck, whereas significantly fewer nerves were observed in acute cholecystitis. Nerve growth alteration may play a role in uncomplicated gallstone pain but the pathology may be different in inflammation.
authors.affiliation: Departments of Surgery, University of Heidelberg, Heidelberg, Germany. rene.hennig@med.uni-heidelberg.de
authors.forename: Rene
authors.initials: R
authors.lastname: Hennig
authors.forename: Jiang
authors.initials: J
authors.lastname: Zanli
authors.forename: Tarek
authors.initials: T
authors.lastname: Osman
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.forename: Tewelde
authors.initials: T
authors.lastname: Berhane
authors.forename: Morten
authors.initials: M
authors.lastname: Vetrhus
authors.forename: Karl
authors.initials: K
authors.lastname: Søndenaa
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005704:Gallbladder / Q000294:innervation* / Q000473:pathology; D042882:Gallstones / Q000150:complications* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009417:Nerve Tissue / Q000254:growth & development* / Q000473:pathology; D010146:Pain / Q000209:etiology*; D043222:Ubiquitin Thiolesterase / Q000276:immunology
chemical_list: C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase