875 TREATMENT WITH A CB2 AGONIST DECREASES SEVERITY OF ESTABLISHED CYSTITIS

Abstract

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2013875 TREATMENT WITH A CB2 AGONIST DECREASES SEVERITY OF ESTABLISHED CYSTITIS Zunyi Wang, Peiqing Wang, and Dale Bjorling Zunyi WangZunyi Wang Madison, WI More articles by this author , Peiqing WangPeiqing Wang Madison, WI More articles by this author , and Dale BjorlingDale Bjorling Madison, WI More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.444AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Painful bladder syndrome is a chronic painful disorder characterized by frequency, urgency, and pain that is estimated to affect 2.7% to 6.5% of American women. The etiology and pathogenesis of painful bladder syndrome remain unknown, and effective treatments are lacking. Cannabinoids exert potent analgesic and anti-inflammatory effects. Cannabinoid receptor 2 (CB2) is expressed in the bladder, particularly in urothelial cells, and bladder inflammation increases CB2 expression. We investigated whether treatment with the selective CB2 agonist GP1a ameliorates severity of cystitis and referred hyperalgesia after induction of cystitis by acrolein. METHODS Cystitis was induced by intravesical instillation of acrolein (0.5 mM, 200 μl) in female C57 mice. Mice were treated with GP1a (Tocris, 10 mg/kg, ip) or vehicle at 3, 24, and 30 hours after instillation of acrolein. Mice were tested for mechanical sensitivity of hind paws at 3, 24, and 48 hours, respectively. Mice were also placed on filter paper for measurement of urine spots at 24 hours. Mice were sacrificed at 48 hours, and bladders were collected, weighed, and processed for histological analysis. RESULTS Forty-eight hours after acrolein, bladders of all animals demonstrated histological evidence of inflammation, primarily characterized by submucosal edema. Mean wet bladder weight (mg/g body weight) was greater in vehicle-treated mice than that in CB2 agonist-treated animals, (2.82 ± 0.17 vs 1.92 ± 0.25, n=5, p < 0.05), and histology revealed that edema was more severe in the vehicle-treated mice. Basal mechanical sensitivity was virtually the same in vehicle- and GP1a-treated mice (2.9 ± 0.01 g). After acrolein, mechanical sensitivity threshold was 0.46 ± 0.13, 0.28 ± 0.03 and 0.54 ± 0.16 g in vehicle-treated group, and was 0.55 ± 0.1, 0.78 ± 0.09 and 1.17 ± 0.41 g in CB2 agonist-treated group at 3, 24 and 48 hours, respectively. The mechanical sensitivity was significantly less (p<0.05, n=5, at 24 and 48 hours) in vehicle-treated than CB2 agonist-treated mice. The number of small diameter urine spots was also significantly reduced; 24.8 ± 6.9 (vehicle-treated) vs 4 ± 3.3 (GP1a-treated), n=5, p < 0.05. CONCLUSIONS Treatment with a selective CB2 agonist after induction of cystitis reduced severity of acrolein-induced cystitis and inhibited bladder inflammation-induced increased peripheral sensitivity to mechanical stimuli. Our data indicate that the CB2 receptor is a potential therapeutic target for treatment of bladder inflammation and subsequent changes in pain perception. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e361 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zunyi Wang Madison, WI More articles by this author Peiqing Wang Madison, WI More articles by this author Dale Bjorling Madison, WI More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...