艾芬地尔鞘内注射对骨癌痛模型小鼠痛行为的改善作用

Intrathecal injection of NR2B antagonist ifenprodil alleviate the bone cancer pain in mouse

目的在小鼠骨癌痛模型上观察鞘内注射N-甲基-D-天冬氨酸受体2B亚基（NR2B）拮抗剂艾芬地尔的镇痛效果。方法将含2×10^5个纤维肉瘤细胞NCTC2472的最小必需培养基（α-MEM）注射到C3H／HeJ小鼠右侧股骨远端骨髓腔，制作骨癌痛模型（T组）。同时设假手术组（s组，n=10），注入不含肿瘤细胞的α-MEM。所有小鼠均于接种前1d，接种后第3，5，7，10，14天检测痛行为学指标，包括自发性抬足次数、机械痛缩足阈值（PWMT）和热痛缩足潜伏期（PWTL）。骨癌痛模型制作成功的T组小鼠在接种后第14天，进一步分为艾芬地尔2．5μg、5．0μg、10．0μg组（11、12、13组，n=10）和对照组（C组，n=10），I1～I3组鞘内注射相应剂量的艾芬地尔，C组及S组给予溶媒，注药体积均为5．0μl，鞘内注射后2h、12h、24h再进行行为学检测。结果与S组[（2．44±0．79）次]和术前基础值[（2．20±0．85）次]相比，肿瘤细胞接种后第14天T组小鼠自发性抬足[（13．16±1．78）次]显著增多（P〈0．05），PWMT[（0．47±0．19）g]较S组[（1．70±0．31）g]和基础值[（1．83±0．23）g]降低（P〈0．05），PWTL[（10．01±1．42）s]较S组[（17．62±1．07）s]和基础值[（18．32±1．57）s]缩短（P〈0．05）；给药后2h、12h，与C组及14d给药前比较，12和B组自发性抬足次数减少（P〈0．05），PWMT增高（P〈0．05），PWTL延长（P〈0．05），且I3组比I2组对痛行为学的改善更显著（P〈0．05）；I1组给药后痛行为学无明显变化（P〉0．05）。结论鞘内注射艾芬地尔有效改善骨癌痛小鼠的痛行为学反应。

Objective To investigate the analgesic effect of intrathecal injection of NR2B antagonist ifenprodil in mouse of bone caner pain. Methods The mouse model of bone cancer pain was developed by intra-femur inoculations of α-minimal essence media （α-MEM） with osteolytic NCTC 2472 cells in C3H/HeJ mice（ group T）. The sham group （group S, n= 10） were inoculated by α-MEM without any cells. Pain ethology indexes such as the spontaneous lifting behaviors, the paw withdrawal mechanical threshold （PWMT） and the paw withdrawal thermal latency （PWTL） were observed on 1 d before inoculation and on 3 d ,5 d ,7 d, 10 d, 14 d after inoculation to evaluate the mouse model of bone cancer. On the 14th d after inoculation, the succeed mouse model of bone cancer pain was divided randomly into 2.5 μg, 5 μg, 10 μg ifenprodil group（ group I1, I2, I3, n = 10） and solventia group （20% DMSO group, group C, n = 10）. Group I1 -I3 were treated by intrathecal injection of corresponding dose of ifenprodil. Group C and group S were treated by intrathecal injection of solventia. All the volume of physic liquor of intrathecal injection was 5 μl. Pain ethology indexes mentioned above was observed at 2 h, 12 h, 24 h after administration. Results （ 1 ） The significant increasing of spontaneous lifting behaviors（ 13.16 ± 1.78）, the obvious decreasing of PWMT （ 0.47 ± 0.19 ） g and PWTL （ 10.01 ± 1.42 ） s were observed on 14th d after inoculation in group T compared with group S and preoperative base level （P 〈 0.05 ）. （2） The spontaneous lifting behaviors [ I2 ： （ 9.00 ± 1.80）, （ 10.90 ± 1.17 ） ; I3 ： （ 6.80 ± 2.51 ）, （ 8.80± 1.64） ] was decreased, the PWMT [ I2 ： （1.12±0.27）g,（0.82±0.30）g;I3：（1.44±0.34）g,（1.16±0.37）g] and PWTL [I2：（13.86±1.51）s, （ 12.12 ± 1.27 ） s ; I3 ： （ 15.95 ± 1.70） s, （ 13.74 ± 1.98 ） s ] was increased in group I2 and 13 compared with the basal level on 14th d before administration and group C at 2 h and I2 h after administration （P〈0.05） The analgesic effect of group I3 was more conspicuous compared with group I2 （P 〈 0.05 ）. No obvious change of pain ethology indexes was observed in group I1 （P 〉 0.05 ）. Conclusion Intrathecal injection of ifenprodil can efficiently relieve mechanical hyperalgia and thermal hyperalgia in the mouse model of bone cancer pain.