title: Cannabinoids ameliorate pain and reduce disease pathology in cerulein-induced acute pancreatitis.
abstract: OBJECTIVE
  The functional involvement of the endocannabinoid system in modulation of pancreatic inflammation, such as acute pancreatitis, has not been studied to date. Moreover, the therapeutic potential of cannabinoids in pancreatitis has not been addressed.
  
  
  METHODS
  We quantified endocannabinoid levels and expression of cannabinoid receptors 1 and 2 (CB1 and CB2) in pancreas biopsies from patients and mice with acute pancreatitis. Functional studies were performed in mice using pharmacological interventions. Histological examination, serological, and molecular analyses (lipase, myeloperoxidase, cytokines, and chemokines) were performed to assess disease pathology and inflammation. Pain resulting from pancreatitis was studied as abdominal hypersensitivity to punctate von Frey stimuli. Behavioral analyses in the open-field, light-dark, and catalepsy tests were performed to judge cannabinoid-induced central side effects.
  
  
  RESULTS
  Patients with acute pancreatitis showed an up-regulation of cannabinoid receptors and elevated levels of endocannabinoids in the pancreas. HU210, a synthetic agonist at CB1 and CB2, abolished abdominal pain associated with pancreatitis and also reduced inflammation and decreased tissue pathology in mice without producing central, adverse effects. Antagonists at CB1- and CB2-receptors were effective in reversing HU210-induced antinociception, whereas a combination of CB1- and CB2-antagonists was required to block the anti-inflammatory effects of HU210 in pancreatitis.
  
  
  CONCLUSIONS
  In humans, acute pancreatitis is associated with up-regulation of ligands as well as receptors of the endocannabinoid system in the pancreas. Furthermore, our results suggest a therapeutic potential for cannabinoids in abolishing pain associated with acute pancreatitis and in partially reducing inflammation and disease pathology in the absence of adverse side effects.
authors.affiliation: Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Michalski
authors.forename: Tamara
authors.initials: T
authors.lastname: Laukert
authors.forename: Danguole
authors.initials: D
authors.lastname: Sauliunaite
authors.forename: Pál
authors.initials: P
authors.lastname: Pacher
authors.forename: Frank
authors.initials: F
authors.lastname: Bergmann
authors.forename: Nitin
authors.initials: N
authors.lastname: Agarwal
authors.forename: Yun
authors.initials: Y
authors.lastname: Su
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Nathalia A
authors.initials: NA
authors.lastname: Giese
authors.forename: Sándor
authors.initials: S
authors.lastname: Bátkai
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
mesh_terms: D000208:Acute Disease; D000818:Animals; D001706:Biopsy; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002186:Cannabinoids / Q000009:adverse effects / Q000627:therapeutic use*; D002108:Ceruletide; D013759:Dronabinol / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D018696:Neuroprotective Agents; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013759:Dronabinol; D002108:Ceruletide; C062018:HU 211