鞘内注射Roscovitine缓解大鼠慢性神经病理性疼痛

Intrathecal injection of roscovitine attenuates chronic neuropathic pain in rats

目的在SD大鼠脊髓后根神经节慢性压迫(CCD)模型上观察鞘内注射Roscovitine的镇痛效果。方法用不锈钢棒(长4mm,直径0.7mm)持续性压迫脊髓背根神经节(DRG)建立慢性神经病理性疼痛模型。术后第7天鞘内注射溶解于DMSO10μl中的Roscovitine50μg(R组);同时设CCD术后第7天只给予鞘内注射二甲基亚砜(DMSO)10μl的CCD组(C组)和非CCD处理、并给予鞘内注射DMSO10μl的假手术组(S组)。三组均于CCD术前、术后第7天(给药前)及给药后2、24、72h检测机械痛缩足阈值(PWMT)和热痛缩足潜伏期(PWTL)。CCD术前及给药后72h用免疫组化技术检测脊髓背角N-甲基-D天冬门氨酸(NMDA)受体2A亚基(NR2A)的表达水平。结果R组和C组给药前PWMT均较术前显著降低[(3.64±0.40)gvs.(14.38±1.53)g,(3.50±0.77)gvs.(13.25±2.21)g],也明显低于S组的(11.31±1.13)g(P<0.05)。R组和C组给药前PWTL均较术前显著缩短[(9.28±1.18)svs.(18.34±1.23)s,(8.91±1.08)svs.(18.59±1.92)s],也短于S组的(18.45±1.44)s(P<0.05)。R组PWMT在给药后24h较给药前和C组显著增加[(7.32±0.69)gvs.(3.64±0.40)g,(3.86±1.14)g](P<0.05),而给药后2hPWTL较给药前和C组显著延长[(15.46±1.51)svs.(9.28±1.18)s,(9.91±1.07)s(P<0.05)。给药后72h,R组脊髓背角NR2A受体表达水平明显低于C组[(0.21±0.02)vs.(0.26±0.01)](P<0.05)。结论鞘内注射Roscovitine能有效改善CCD大鼠痛行为学反应;其作用可能与抑制脊髓背角NR2A受体表达有关。

Objective To investigate the analgesic effect of intrathecal injection of roscovitine in rats with chronic neuropathic pain. Methods The rat model of chronic compression of dorsal root ganglion（CCD） was developed by a constant oppression on the spinal cord dorsal root ganglia （DRG） with a stainless steel rod（4 mm in length and 0. 7 mm in diameter ） inserted into the intervertebral foramen between L4-6. On the 7^th postoperative day,the rats were intrathecally injected roscovitine 50 tzg（dissolved in 20% DMSO 5 μl）（group R） or 20%DMSO 5 μl （group C）. The rats in sham operation group（group S） were intrathecally injected 20% DMSO 5μl only. The paw withdrawal mechanical threshold （PWMT） and paw withdrawal thermal latency （PWTL） were tested before operation, on the 7^th clay after operation and at 2 h,24 h,72 h after intrathecal injection. Results PWMT was lower on the 7^th day after operation than that before operation in group R and group C [（3.64±0.40） g vs. （14.38±1.53） g and （3.50±0. 77） g vs. （13.25±2. 21） g] and that in group S [（11.31±1.13） g] （P〈0.05）. PWTL was shorter on the 7^th day after operation than that before operation in group R and group C[（9. 28±1.18） s vs. （18.34±1.23） s and （8.91±1.08） s vs. （ 18.59±1.92 ） s] and that in group S [（18.45±1.44 ） s]（P〈0; 05）. PWMT in group R was significantly increased at 24 h after drug injection [（7.32±0.69） g] compared with that on the 7^th day after operation [（3.64±0.40） g] and that in group C[（3.86 ± 1.14） g] （P〈0.05）. PWTL in group R was significantly prolonged at 2 h after drug injection [（15.46± 1.51） s] compared with that on the 7^th day after operation [（9.28±1.18） s] and that in group C [（9.91±1.07） s]（P〈0.05）. The expression of NR2A receptor in the DRG was significantly lower in group R at 72 h after drug injection than that in group C [（0. 21± 0. 02） vs. （0. 26 ± 0. 01）] （P〈 0. 05） . Conclusion Intrathecal injection of roscovitine can efficiently attenuate mechanical neuropathic pain in rats with CCD, which may be ralated to its inhibitory effect on the expression of NR2A receptor in the DRG.