国际麻醉学与复苏杂志   2016, Issue (6): 2-2
    
鞘内注射突触后致密物质-95反义寡核苷酸对神经病理性疼痛小鼠痛行为学的影响
王存金, 王红军, 张励才1()
1.徐州医学院 江苏省麻醉学重点实验室,江苏省麻醉与镇痛应用技术重点实验室
Effects of intrathecally postsynaptic density protein-95 antisense oligodeoxynucleotide on pain behaviors in mice model of neuropathic pain
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摘要:

目的 探讨鞘内给予突触后致密物质?蛳95(postsynaptic density protein-95, PSD-95)反义寡核苷酸对坐骨神经结扎小鼠疼痛行为的影响。 方法 选取鞘内置管成功的C57BL/6雄性小鼠48只,采用随机数字表法分为4组(每组12只):假手术组(Sham组)、生理盐水组(NS组)、PSD-95反义寡核苷酸组(A组)、PSD?蛳95错义寡核苷酸组(M组)。采用结扎坐骨神经的方法制备小鼠坐骨神经慢性压迫性损伤(chronic constriction injury, CCI)模型,结扎坐骨神经后第1~14天,NS组、A组、M组分别鞘内注射生理盐水5 μl、反义寡核苷酸5 μg/5 μl、错义寡核苷酸5 μg/5 μl,1次/d。于术前1 d及术后1、3、5、7、14、17、21 d测定小鼠结扎侧足底机械缩足反射阈值(paw withdrawal mechanical threshold, PWMT)和热缩足潜伏期(paw withdrawal thermal latency, PWL)。 结果 A组小鼠术后1~14 d的疼痛阈值与Sham组维持一致[第14天,PWMT (5.69±1.34) g,P>0.05;PWL(9.65±1.44) s,P>0.05]。术后17 d,A组小鼠损伤侧足出现疼痛[PWMT (4.24±1.83) g,P<0.05;PWL (7.18±0.41) s,P<0.05],但是与NS组[PWMT (1.77±0.38) g,P<0.05;PWL (4.33±1.21) s,P<0.05]、M组[PWMT (1.6±0.37) g,P<0.05;PWL (4.38±0.95) s,P<0.05]比较,疼痛明显减轻,并且持续到术后第21天。 结论 在CCI所致神经病理性疼痛的发展阶段,连续鞘内给予PSD-95反义寡核苷酸可以完全逆转给药期内小鼠痛行为表现,并且在停止给药后7 d仍有明显缓解疼痛的作用。

关键词: 神经病理性疼痛; 突触后致密物质-95; 反义寡核苷酸; N-甲基-D-天冬氨酸
Abstract:

Objective To investigate the effects of intrathecally postsynaptic density protein-95 (PSD-95) antisense oligodeoxynucleotide on neuropathic pain behaviors of sciatic nerve ligation mouse. Methods Forty-eight male C57BL/6 mice in which intrathecal catheter was successfully implanted were randomly divided into 4 groups (n=12): Sham group, normal saline group (group NS), PSD-95 antisense oligodeoxynucleotide group (group A) and PSD-95 missense oligodeoxynucleotide group (group M). In groups NS, A and M, normal saline 5 μl, antisense oligodeoxynucleotide 5 μg/5 μl and missense oligodeoxynucleotide 5 μg/5 μl were injected intrathecally once a day for 14 d, starting from the 1st day after chronic constriction injury(CCI), respectively. Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWL) were measured on day 1 before CCI and on day 1, 3, 5, 7, 14, 17, 21 after CCI. Results During day 1-day 14, mice in group A maintained the pain thresholds consistent with Sham group[14 d, PWMT(5.69±1.34) g, P>0.05, PWL (9.65±1.44) s, P>0.05]. The withdrawal thresholds in the ipsilateral hind paws of the group A were significantly lower than sham group on day 17 after CCI[PWMT(4.24±1.83) g, P<0.05, PWL(7.18±0.41) s, P<0.05]. However, compared with group NS [PWMT (1.77±0.38) g, P<0.05, PWL (4.33±1.21) s, P<0.05] and group M[PWMT (1.6±0.37) g, P<0.05, PWL(4.38±0.95) s, P<0.05], the withdrawal thresholds of group A was significantly elevated on day 17 after CCI. Conclusions Intrathecally treated with PSD-95 antisense oligodeoxynucleotide in the development of neuropathic pain induced by CCI completely improved pain behaviors during the course of injection, and the effects of pain relief lasted at least 7 d after no injection.

Key words: Neuropathic pain; postsynaptic density protein-95; Antisense oligonucleotide; N?-methyl-D-aspartate