目的探讨大麻素受体2(cannabinoid receptor2,CB2R)激动剂JWH015对瑞芬太尼诱发的切口痛模型大鼠痛觉过敏的影响。方法60只雄性sD大鼠采用随机数字表法随机分成2大组:鞘内给药组和腹腔给药组。每大组又随机分为5小组:鞘内给药组分为对照组1(C1组)、切口痛组1(I1组)、瑞芬太尼组1(R1组)、切口痛+JWH015组(QI组)、切口痛+瑞芬太尼+JWH015组(QR组);腹腔给药组分为对照组2(C2组)、切口痛组2(12组)、瑞芬太尼组2(R2组)、切口痛+JWH015组(FI组),切口痛+瑞芬太尼、+JWH015组(FR组),每组6只。QI组与QR组在造模前30min鞘内注射10ug JWH015,C1、I1、R1组均鞘内给予20%的二甲基亚砜(DMSO)溶液,容积均为10ul;而FI组与FR组在造模前30min腹腔注射100ug JWH015,C2、12、R2组均腹腔给予4%的DMSO溶液,容积均为0.5ml。除C1/C2组外,其余各组均制作切口痛模型,R1/R2组、QR组和FR组在造模的同时皮下泵注瑞芬太尼0.04mg/kg,其余组皮下泵注生理盐水,容积均为0.4ml,30min泵完。测量术前24h及术后2,6,24,48h大鼠手术切口同侧后爪的机械缩足反射阈值(PWMT)及热缩足潜伏期(PWTL)。结果与C1/C2组和基础值比较,11/12组术后PWMT,和PWTL均降低(P〈0.01);与11/12组比较,R1/R2组术后PWMT和PWTL均明显降低(P〈0.05);与R1/IR2组相比,QR组从术后6h的PWMT[(7.78±1.09)g]和PWTL[(17.28±1.58)S]开始明显升高(P〈0.05),与FR组在术后6h、24h和48h的PWMT[(7.79±0.72)g,(9.50±1.17)g,(7.86±1.16)g]和PWTL[(16.23±1.50)s,(19.53±1.63)S,(18.10±0.93)s]升高的结果一致。结论鞘内及腹腔注射JWH015均可以有效缓解由瑞芬太尼诱发的切口周围组织痛觉过敏。
Objective To investigate the effects of cannabinoid receptor 2 (cannabinoid receptor 2, CB2R) agonist JWHO15 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 JWHO15 groups (QI and FI), remifentanil groups (R1 and R2), and JWHO15 plus remifentanil groups ( QR and FR). Rats in group QI/QR and FI/FR were intrathccal injection with lOp.g JWHO15 ( diluted in 10ul 20% DMSO solution) and intraperitoneal administration with 100ug JWHO15 ( diluted in 10ul 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 1 ,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 JWH015 in this investigation dose could relief remifentanil-induced