title: Pain mechanisms in chronic pancreatitis: of a master and his fire.
abstract: BACKGROUND
  Unraveling the mechanisms of pain in chronic pancreatitis (CP) remains a true challenge. The rapid development of pancreatic surgery in the twentieth century, usage of advanced molecular biological techniques, and emergence of clinician-scientists have enabled the elucidation of several mechanisms that lead to the chronic, complicated neuropathic pain syndrome in CP. However, the proper analysis of pain in CP should include three main arms of mechanisms: "peripheral nociception," "peripheral/pancreatic neuropathy and neuroplasticity," and "central neuropathy and neuroplasticity."
  
  
  CONCLUSIONS
  According to our current knowledge, pain in CP involves sustained sensitization of pancreatic peripheral nociceptors by neurotransmitters and neurotrophic factors following neural damage. This peripheral pancreatic neuropathy leads to intrapancreatic neuroplastic alterations that involve a profound switch in the autonomic innervation of the human pancreas via "neural remodeling." Furthermore, this neuropathy entails a hyperexcitability of spinal sensory second-order neurons, which are subject to modulation from the brainstem via descending facilitation. Finally, viscerosensory cortical areas react to this central sensitization via spatial reorganization and thus a central neuroplasticity. The present review summarizes the current findings in these arms of mechanisms and introduces a novel concept to consistently describe pain in CP as a "predominantly neuropathic," "mixed-type" pain.
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. demir@chir.med.tu-muenchen.de
authors.forename: Ihsan Ekin
authors.initials: IE
authors.lastname: Demir
authors.forename: Elke
authors.initials: E
authors.lastname: Tieftrunk
authors.forename: Matthias
authors.initials: M
authors.lastname: Maak
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Güralp Onur
authors.initials: GO
authors.lastname: Ceyhan
mesh_terms: D015746:Abdominal Pain / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D009437:Neuralgia / Q000209:etiology / Q000503:physiopathology*; D009619:Nociceptors / Q000502:physiology; D010147:Pain Measurement; D050500:Pancreatitis, Chronic / Q000150:complications*