Effect of intrathecal injection JWH015 on the remifentani-induced hyperalgesia in rats

Abstract

Objective To investigate the effect of cannabinoid receptor 2 (CB2R) agonist JWH015 on the hyperalgesia induced by remifentanil in a rat model of incision pain. Methods Thirty Sprague-Dawley (SD) rats were randomly divided into 5 groups (n=6):control group(group C),incisional pain group(group I),incisional pain plus JWH015 group (group JI),remifentanil group (group R),and JWH015 plus remifentanil group (group JR).10 μg JWH015 diluted by 10 μl 20％ dimethyl sulfoxide (DMSO)solution was intrathecally injected in each rat of group JI and JR 30 min before plantar incision,while group C,I and R received the equivalent amount of normal saline 20％ DMSO 10 μl in the same way.Plantar incision surgery was operated in group I,R,JI,and JR.In group R and JR,remifentanil (0.04 mg/kg,0.4 ml) was infused subcutaneously with a pump for 30 min at the moment of surgical incision.The other groups were received the equivalent amount of normal saline (0.4 ml) instead of remifentanil.The paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measurd one day before and at 2,6,24 and 48 h after incision. Results Compared with group C and the baseline,the level of PWMT and PWTL significantly decreased at 2,6,24 and 48 h after incision in group I (P＜0.05); Compared with group I,the significant decrease of PWMT (6.3±0.8),(6.4±0.8),(6.3± 1.0),(6.8±0.9) g and PWTL( 12.8± 1.2),(12.2±0.9),( 13.4± 1.1 ),( 13.5± 1.3 ) s were observed after incision in group R (P＜0.05).Compared with group R,the significant increase of PWMT (7.9±1.0),(9.9±1.1),(8.4±1.1) g and PWTL (17.3±1.9),(19.9±1.3),(17.7±1.2) s were observed at 6,24 and 48 h after incision in group JR (P＜0.05). Conclusions Intrathecal injection of JWH015 can be effectively alleviated remifentanil-induced hyperalgesia in a rat model of incision pain. Key words: Cannabinoids; Cannabinoid receptor 2; JWH015; Remifentanil; Hyperalgesia