Cannabinoid receptor 2 activation decreases severity of cyclophosphamide‐induced cystitis via regulating autophagy

Purpose Cannabinoids have been shown to exert analgesic and anti‐inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1 and CB2). The objective of this study was to determine efficacy and mechanism of CB2 activation on cyclophosphamide (CYP)‐induced cystitis in vivo. Methods Cystitis was induced by intraperitoneal (IP) injection of CYP in female C57BL/6J mice. Mice were pretreated with CB2 agonist JWH‐133 (1 mg/kg, intraperitoneally), CB2 antagonist AM‐630 (1 mg/kg, intraperitoneally) or autophagy inhibitor 3‐methyladenine (3‐MA) (50 mM, intraperitoneally) before IP injection of CYP. Peripheral nociception and spontaneous voiding were investigated in these mice. Bladders were collected, weighed, and processed for real‐time polymerase chain reaction, immunoblotting analysis, histological and immunohistochemical analysis. Results Twenty‐four hours after IP injection of CYP, the bladder of CYP‐treated mice showed histological evidence of inflammation. The expression of CB2 in bladder was significantly increased in CYP‐treated mice. Mechanical sensitivity was significantly increased in CYP‐treated mice and CB2 agonist JWH‐133 attenuated this effect (P