title: Treatment with a cannabinoid receptor 2 agonist decreases severity of established cystitis.
abstract: OBJECTIVE
  We investigated whether treatment with the selective cannabinoid receptor 2 agonist GP1a would ameliorate the severity of experimental cystitis. We determined the association of referred hyperalgesia and increased urinary frequency after establishing cystitis in mice by intravesical instillation of acrolein.
  
  
  METHODS
  Cystitis was induced by intravesical instillation of acrolein in female C57BL/6NH mice. Mice were treated with GP1a (10 mg/kg intraperitoneally) or vehicle 3.5, 22 and 30 hours after instillation of acrolein. Mice were tested for mechanical sensitivity of hind paws. Short-term voluntary voiding was assessed by quantifying urine spots of freely moving mice. Bladders were collected, weighed and processed for immunohistochemical, histological and immunoblotting analysis.
  
  
  RESULTS
  At 48 hours after acrolein instillation the bladder of all mice showed histological evidence of inflammation. The severity of edema and increase in bladder weight were inhibited in cannabinoid receptor 2 agonist treated animals (p <0.05). Neither cystitis nor treatment with GP1a or AM630 (selective cannabinoid receptor 2 antagonist) plus GP1a appeared to alter cannabinoid receptor 2-like immunoreactivity abundance in urothelium. Mechanical sensitivity was significantly increased after acrolein and the increase was attenuated in cannabinoid receptor 2 agonist treated mice (p <0.05). The number of small diameter urine spots was significantly increased after acrolein and treatment with GP1a attenuated this increase (p <0.05). GP1a effects were prevented by AM630.
  
  
  CONCLUSIONS
  Treatment with a selective cannabinoid receptor 2 agonist decreased severity of established acrolein induced cystitis and inhibited bladder inflammation associated increased referred mechanical sensitivity and increased bladder urinary frequency. Our data indicate that cannabinoid receptor 2 is a potential therapeutic target for treatment of painful inflammatory bladder diseases.
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, Madison, Wisconsin. Electronic address: wangz@svm.vetmed.wisc.edu.
authors.forename: Zun-Yi
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, Madison, Wisconsin.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, Madison, Wisconsin; Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bjorling
mesh_terms: D000818:Animals; D003556:Cystitis / Q000188:drug therapy*; D005260:Female; D007192:Indenes / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D011720:Pyrazoles / Q000627:therapeutic use*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D012720:Severity of Illness Index
chemical_list: D007192:Indenes; C553580:N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-1,4-dihydro-6-methylindeno(1,2-c)pyrazole-3-carboxamide; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2
keywords: N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-1,4-dihydro-6-methylindeno(1,2-c)pyrazole-3-carboxamide; cannabinoid receptor agonists; cystitis; interstitial; mice; urinary bladder