The effect of cannabinoid receptor 2 agonist JWH015 on the hyperalgesia induced by remifentanil

Objective To investigate the effects of cannabinoid receptor 2 (cannabinoid receptor 2, CB2R) agonist JWHOl5 on the hyperalgesia induced by remifentanil in a rat model of postoperative pain. Methods Sixty SD rats were randomly divided into 10 groups (n=6 each): control groups (C1 and C2), incisional pain groups (I1 and I2), incisional pain plus JWHOl5 groups (QI and FI), remifentanil groups (R1 and R2), and JWHOl5 plus remifentanil groups (QR and FR). Rats in group QI/QR and FI/FR were intrathecal injection with 10μg JWHOl5 (diluted in 10μl 20% DMSO solution) and intraperitoneal administration with 100μg JWHOl5 (diluted in 10μl 4% DMSO solution) respectively 30 min before plantar incision while rats in group C, I and R were received with the same volume of DMSO solution. Plantar incision surgery was operated in rats of group I, R, QI/FI, and QR/FR. In group R and QR/FR, remifentanil (0.04 mg/kg) was infused subcutaneously to rats with a pump for 30 min at the moment of surgical incision. The paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) at 24 h before incision and at 2 h, 6 h, 24 h and 48 h after incision were tested to evaluate the behavioral changes. Results Compared with group C and baseline, the level of PWMT and PWTL decreased at 2 h, 6 h, 24 h and 48h after incision in group I (P<0.01); Compared with group I , the significant decrease of PWMT and PWTL were observed after incision in group R (P<0.05); Compared with group R, the significant increase of PWMT (7.78±1.09) and PWTL (17.28±1.58) were observed from 6 h after incision in group QR(P<0.05). And the increase of PWMT (7.79±0.72, 9.50±1.17, 7.86±1.16) and PWTL (16.23±1.50, 19.53±1.63, 18.10±0.93) were observed at 6 h, 24 h and 48 h after incision in group FR(P<0.05). Conclusion Intrathecal and intraperitoneal administration of JWHOl5 in this investigation dose could relief remifentanil-induced hyperalgesia in a rat model of postoperative pain. Key words: Cannabinoid; Cannabinoid receptor 2; JWH015; Remifentanil; Hyperalgesia