title: Pancreatic nociception--revisiting the physiology and pathophysiology.
abstract: BACKGROUND
  Pain management of many pancreatic diseases remains a major clinical concern. This problem reflects our poor understanding of pain signaling from the pancreas.
  
  
  OBJECTIVE
  This review provides an overview of our current knowledge, with emphasis on current pain management strategies and recent experimental findings.
  
  
  METHODS
  A systematic search of the scientific literature was carried out using EMBASE, PubMed/MEDLINE, and the Cochrane Central Register of Controlled Trials for the years 1965-2011 to obtain access to all publications, especially randomized controlled trials, systematic reviews, and meta-analyses exploring pain and its management in disease states such as acute pancreatitis (AP), chronic pancreatitis (CP) and pancreatic cancer (PC).
  
  
  RESULTS
  Over the last decade, numerous molecular mediators such as nerve growth factor and the transient receptor potential (TRP) cation channel family have been implicated in afferent nerve signaling. More recent animal studies have indicated the location of the receptive fields for the afferent nerves in the pancreas and shown that these are activated by agents including cholecystokinin octapeptide, 5-hydroxytryptamine and bradykinin. Studies with PC specimens have shown that neuro-immune interactions occur and numerous agents including TRP cation channel V1, artemin and fractalkine have been implicated. Experimental studies in the clinical setting have demonstrated impairment of inhibitory pain modulation from supraspinal structures and implicated neuropathic pain mechanisms.
  
  
  CONCLUSIONS
  Our knowledge in this area remains incomplete. Characterization of the mediators and receptors/ion channels on the sensory nerve terminals are required in order to facilitate the development of new pharmaceutical treatments for AP and CP.
authors.affiliation: Department of Surgery, Modbury Hospital, South Australia, Australia.
authors.forename: Savio G
authors.initials: SG
authors.lastname: Barreto
authors.forename: Gino T P
authors.initials: GT
authors.lastname: Saccone
mesh_terms: D000208:Acute Disease; D016206:Databases, Bibliographic; D006801:Humans; D059225:Nociception / Q000502:physiology*; D059408:Pain Management; D010179:Pancreas / Q000503:physiopathology*; D010190:Pancreatic Neoplasms / Q000150:complications / Q000503:physiopathology; D050500:Pancreatitis, Chronic / Q000150:complications / Q000503:physiopathology; D059265:Visceral Pain / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy