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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 observe the analgesic effect of intrathecal injection of roscovitine on chronic spinal cord compression (CCD) model of spinal cord in SD rats. Methods Chronic neuropathic pain models were established by continuous compression of the dorsal root ganglion (DRG) with a stainless steel rod (4 mm in length and 0.7 mm in diameter). Roscovitine 50 μg (R group) dissolved in 10 μl of DMSO was intrathecally injected on the 7th day after the operation, and only 10 μl of dimethylsulfoxide (DMSO) administered intrathecally to the CCD group (group C) CCD treatment, and a sham operation group (group S) of intrathecal injection of DMSO 10 μl was given. The three groups were detected before mechanical and postoperative 7 days (before administration) and 2,24,72 h after administration of mechanical acuity threshold (PWMT) and thermal contraction foot latency (PWTL). The expression of N-methyl-D aspartate (NMDA) receptor 2A subunit (NR2A) in spinal dorsal horn was detected by immunohistochemical technique before operation and at 72h after administration. Results Before treatment, the values of PWMT in group R and group C were significantly lower than those before operation [(3.64 ± 0.40) g vs (14.38 ± 1.53) g and (3.50 ± 0.77) gvs. (13.25 ± 2.21) g], respectively S group (11.31 ± 1.13) g (P <0.05). The PWTL in group R and group C before treatment were significantly shorter than those in group S [(9.28 ± 1.18) svs. (18.34 ± 1.23) s, (8.91 ± 1.08) svs. (18.59 ± 1.92) s] (18.45 ± 1.44) s (P <0.05). The PWMT of group R increased significantly (P <0.05) at 24 h after administration compared with that before administration and at C group [(7.32 ± 0.69) vs 3.64 ± 0.40 g vs (3.86 ± 1.14) g] (P <0.05) compared with pre-administration and C group [(15.46 ± 1.51) svs. (9.28 ± 1.18) s, (9.91 ± 1.07) s) At 72h after administration, the expression of NR2A receptor in spinal dorsal horn of R group was significantly lower than that in C group [(0.21 ± 0.02) vs. (0.26 ± 0.01)] (P <0.05). Conclusion Intrathecal injection of Roscovitine can effectively improve the painful behavior of CCD rats, which may be related to the inhibition of NR2A receptor expression in spinal dorsal horn.