title: Pancreatic neuropathy and neuropathic pain--a comprehensive pathomorphological study of 546 cases.
abstract: OBJECTIVE
  Chronic pancreatitis (CP) and pancreatic adenocarcinoma (PCa) are characterized by intrapancreatic neural alterations and pain. Our aims were to: (a) Investigate whether neuropathic changes like pancreatic neuritis, increased neural density, and hypertrophy are phenomena only in CP or whether they are also evident in other pancreatic disorders as well, (b) study possible variations in neural cancer cell invasion among malignant pancreatic tumors, and (c) explore whether these neuropathic changes contribute to pain sensation.
  
  
  METHODS
  Neuropathic changes were studied in PCa (n=149), in CP (n=141), in pancreatic tumors (PTm) including serous/mucinous cystadenomas, invasive/noninvasive intraductal papillary mucinous neoplasias, benign/malignant neuroendocrine tumors, ampullary cancers (n=196), and in normal pancreas (n=60). The results were correlated with GAP-43 expression, tissue inflammation, pancreatic neuritis, neural invasion, fibrosis, desmoplasia, pain, and patient survival.
  
  
  RESULTS
  Increased neural density and hypertrophy were only detected in PCa and CP and were strongly associated with GAP-43 over expression and abdominal pain. The severity of pancreatic neuritis was strongest in PCa and was closely linked to changes in neural density and hypertrophy. The aggressiveness of neural cancer cell invasion was most prominent in PCa and was related to neuropathic changes, desmoplasia, and pain. Severe and enduring pain were strongly associated with poor prognosis in PCa patients.
  
  
  CONCLUSIONS
  Enhanced neural density and hypertrophy are only typical features of CP and PCa among all investigated pancreatic disorders. Such neuropathic changes, including damage to nerves by inflammatory and/or cancer cells, seem to enhance and generate pancreatic neuropathic pain.
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Güralp O
authors.initials: GO
authors.lastname: Ceyhan
authors.forename: Frank
authors.initials: F
authors.lastname: Bergmann
authors.forename: Mustafa
authors.initials: M
authors.lastname: Kadihasanoglu
authors.forename: Burak
authors.initials: B
authors.lastname: Altintas
authors.forename: Ihsan E
authors.initials: IE
authors.lastname: Demir
authors.forename: Ulf
authors.initials: U
authors.lastname: Hinz
authors.forename: Michael W
authors.initials: MW
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Nathalia A
authors.initials: NA
authors.lastname: Giese
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
mesh_terms: D015746:Abdominal Pain / Q000209:etiology*; D000230:Adenocarcinoma / Q000473:pathology*; D005355:Fibrosis; D019922:GAP-43 Protein / Q000032:analysis; D006801:Humans; D006984:Hypertrophy; D009361:Neoplasm Invasiveness; D009443:Neuritis / Q000473:pathology*; D009473:Neuronal Plasticity; D010179:Pancreas / Q000294:innervation* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000401:mortality / Q000473:pathology*
chemical_list: D019922:GAP-43 Protein