【摘要】 目的 在大鼠切口痛模型基础上探讨大麻素受体2(cannabinoid receptor 2,CB2R)激动剂JWH015对瑞芬太尼诱发的痛觉过敏的影响。 方法30只雄性SD大鼠采用随机数字表法随机分成5组：对照组（C组）,切口痛组（I组）,瑞芬太尼组（R组）,切口痛+JWH015组（JI组）,切口痛+瑞芬太尼+JWH015组（JR组）,每组6只。JI组与JR组在造模前30 min鞘内注射10μg JWH015，而C、I、R组均给予20﹪的二甲基亚砜（Dimethyl sulfoxide，DMSO）溶液，容积均为10 μl。除C组外，其余各组均制作切口痛模型，R组和JR 组在造模的同时皮下泵注瑞芬太尼0.04 mg/kg，其余组皮下泵注生理盐水 ，容积均为0.4 ml，30 min泵完。测定术前24 h及术后2、6、24和48 h大鼠切口手术同侧后爪的机械缩足反射阈值（PWMT）和热缩足反射潜伏期（PWTL）。结果 与C组和基础值比较，I组术后各时间点PWMT和PWTL均降低（P<0.05）；与I组比较，R组术后各时间点PWMT（6.29±0.84、6.38±0.83、6.32±1.05、6.82±0.93）和PWTL（12.83±1.18、12.20±0.94、13.37±1.09、13.52±1.28）均明显降低（P<0.05）；与R组相比，JR组术后6，24和48 h的PWMT（7.92±1.07、9.94±1.09、8.39±1.14）和PWTL（17.27±1.90、19.91±1.26、17.65±1.18）明显升高（P<0.05）。结论 鞘内注射JWH-015可以有效缓解由瑞芬太尼诱发的切口周围组织痛觉过敏。
【Abstract】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 Thirty SD rats were randomly divided into 5 groups (n=6 each): control group (C), incisional pain group (I), incisional pain plus JWHOl5 group (JI), remifentanil group (R), and JWHOl5 plus remifentanil group (JR). Rats in group J and JR were intrathecal injection with 10μg JWHOl5 (diluted in 10μl 20% DMSO solution) 30 min before plantar incision while rats in group C, I and R were received with the same volume of 20% DMSO solution. Plantar incision surgery was operated in rats of group I, R, JI, and JR. In group R and JR, 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 The level of PWMT and PWTL among every group had no difference before operation (P>0.05). 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<0.05)；Compared with group I , the significant decrease of PWMT(6.29±0.84、6.38±0.83、6.32±1.05、6.82±0.93)and PWTL(12.83±1.18、12.20±0.94、13.37±1.09、13.52±1.28)were observed after incision in group R (P<0.05), but there was no difference between group I and group JI at every measured time(P>0.05). Compared with group R, the significant increase of PWMT (7.92±1.07、9.94±1.09、8.39±1.14) and PWTL (17.27±1.90、19.91±1.26、17.65±1.18) were observed at 6 h,24 h and 48 h after incision in group JR(P<0.05). Conclusions Intrathecal injection of JWHOl5 in this investigation dose could relief remifentanil-induced hyperalgesia in a rat model of postoperative pain.
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