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

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溶骨性纤维肉瘤细胞，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DMSO5μl和溶于20％DMSO的JWH0151μg；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。

Objective 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 JWHO15 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 3 d, 5 d, 7 d, 10d, 14d after inoculations. Also, the same tests were performed at lh,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.