鞘内注射大麻素受体2激动剂JWH015对骨癌痛小鼠痛行为的影响
The effect of intrathecal injection JWH015 on pain behavior in a mouse model of bone cancer pain
摘要目的 观察鞘内注射大麻素受体2(CB2)激动剂JWH015对骨癌痛小鼠痛行为的影响.方法 雄性C3H/HeN小鼠32只随机分为4组(n=8):空白组(C),假手术组(s),DMSO(D,二甲基亚砜)组和JWH015(J)组.D组和J组在小鼠右侧股骨远端骨髓腔接种溶于最小必需培养基(α-MEM)的NCTC2472谘骨性纤维肉瘤细胞,建立骨癌痛模型;s组接种不含细胞的α-MEM;c组不予任何处理.在接种肿瘤细胞后的第14天按照分组D组和J组分别鞘内注射DMSO 5μl和溶于20%DMSO的JWH015 1 μg;S组注射DMSO.各组于接种前,接种后的3d、5d、7d、10d、14d以及给药后的1h、6h、24h、48h、72h测定小鼠的机械性缩足阈值(FWMT)和热缩腿潜伏期(FWTL).结果 与术后14d给药前的基础值[PWMT(0.45±0.09)g,PWTL(11.87±1.1)s]相比,鞘内注射JWH015后6h小鼠骨癌痛即缓解[PWMT(1.20±0.21)g,PWTL(15.35±2.42)s](P<0.05);24h缓解作用达到高峰[PWMT(1.85±0.28)g,PWTL(18.80±2.93)s](P<0.05);在72h作用衰退到给药前水平[PWMT(0.48±0.10)g,PWTL(11.83±1.19)s]P>0.05).结论 鞘内注射JWH015能够显著改善骨癌痛小鼠的痛行为.
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abstractsObjective To investigate effect of intrathecal injection JWH015 on pain behavior in a mouse model of bone cancer pain. Methods 32 male C3H/HeN mice weighing 20~25g were randomly divided into 4 groups (n = 8) : control group(C) ,sham group(S) ,DMSO group(D) and JWH015 group(J). Group D and group J were induced mouse models of bone cancer pain by intra-right-femur inoculations of osteolytic NCTC2472 cells while group S were injected only α-MEM and group C were done nothing. On the 14d after inoculations, group D and group J accepted intrathecal injection of DMSO and 1 μg JWH015 which dissolved in 5 μl DMSO, respectively. Mouse accepted pain behavior tests including paw withdrawal mechanical threshold (FWMT) and paw withdrawal thermal latency ( FWTL) before and at 3d ,5d,7d, 10d, 14d after inoculations. Also, the same tests were performed at 1h, 6h, 24h, 48h, 72h, after administration. Results Compared with before administration [PWMT(0. 45 ± 0. 09) g, PWTL( 11.87 ± 1.1) s ] , the mice of group J showed significant pain relief at 6h[ PWMT(1.20 ± 0.21) g, PWTL(15.35 ± 2. 42) s, P < 0. 05 ], the effect of JWH015 reached its peak at 24h [ PWMT(1. 85 ± 0. 28) g, PWTL(18.80 ±2.93)s, P<0.05], while declined at 72h [PWMT(0.48 ±0.10)g, PWTL(11.83 ±1.19)s, P> 0.05]. No obvious change of pain behavior was observed in group D (P > 0.05 ). Conclusion Intrathecal injection JWH015 attenuated bone cancer pain.
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