鞘内注射Cav3.3反义寡聚核苷酸对CCD大鼠痛阈的影响

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【摘要】 目的 观察鞘内注射cav3.3反义寡聚核苷酸对慢性背根节压迫(chronic compression of dorsal root ganglion,ccd)大鼠痛阈的影响，探讨脊髓Cav3.3T型钙通道在神经病理痛中的作用。方法 鞘内置管的雄性SD大鼠32只，随机分为4组(行为学n＝8，)：CCD＋NS组、CCD+Cav3.3反义核苷酸组(CCD+Cav3.3AS)、CCD+Cav3.3错义核苷酸组(CCD+Cav3.3MM)、假手术(sham)＋NS组。各组大鼠在CCD或sham后第1天开始连续4 d每天两次鞘内分别注射Cav3.3AS、Cav3.3MM 12.5 μg/10 μl或NS 10 μl，行为学部分分别观察术后1、3、5、7、10、14 d大鼠机械缩足阈值(mechanical withdrawal threshold,MWT)和热缩足潜伏期(thermal withdrawal latency，TWL)。 结果 鞘内注射Cav3.3反义寡聚核苷酸能显著延缓CCD大鼠痛敏的形成，在CCD术后10 d才形成与CCD＋NS组类似的痛敏，而鞘内注射Cav3.3错义核苷酸则与NS组无统计学差异。结论 脊髓Cav3.3参与神经病理痛的形成，抑制脊髓Cav3.3基因的表达具有疼痛治疗作用。

【关键词】 神经病理痛；T 型钙通道；慢性背根节压迫；脊髓

Pain threshold in CCD rat following intrathecal administration Cav3.3 antisence oligonucleotide LI Zhangjun,FANG Zhiyuan, ZENG Yinming, et al.Department of Anesthesiology,the First Peoples Hospital of Changzhou,Changzhou 213003,China

【Abstract】 Objective To investigate the role of the Cav3.3 in spinal cord in the development of the neuropathic pain，to we observed the effect of Cav3.3antisence oligonucleotide intrathecally administered on the pain threshold of the rats following chronic compression of dorsal root ganglion. Methods Thirty two male SD rats after implanted catheter intrathecally were divided into four groups(ethology n=8,): CCD+NS groups, CCD + Cav3.3 antisence oligonucleotide (CCD+Cav3.3AS) group,CCD + Cav3.3 mismatch oligonucleotide (CCD+Cav3.3MM) group,sham + NS group.The rats in every group were intrathecally administered respectively Cav3.3AS,CCD+Cav3.3MM twice a day from postoperation 1 day to 4 day with 12.5 μｇ/10 μl or 10 μl NS. Measured mechanical withdrawal threshold and thermal withdrawal latency of rats in every group before operation and postoperation 1,3,5,7,10 and 14 days with von Frey hair. Results Cav3.3AS intrathecally administered can delay the development of the CCD rats, and it was until postoperation 10 day the MWT and TWL of the rats in Cav3.3AS group became similar with the CCD+NS group, however, the MWT and TWL of the rats in Cav3.3MM group had no significance difference VS CCD+NS group. Conclusion Cav3.3 T channel may have important role in the development of the neuropathic pain and inhibiting the expression of spinal cord Cav3.3 gene may contribute to the treatment of the neuropathic pain.

【Key words】 Neuropathic pain;T type calcium channels； Chronic compression of dorsal root ganglion；Spinal cord

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作者单位：213003 常州市第一人民医院麻醉科/徐州医学院江苏省麻醉学重点实验室(李张军)；徐州医学院江苏省麻醉医学研究所(曾因明 文先杰)；苏州市立医院麻醉科(方志源) 近年来，T型钙通道在神经病理性疼痛中的作用受到人们普遍关注，我们以前的研究发现，鞘内注射T型钙通道阻断剂米贝地尔能使慢性坐骨神经松结扎大鼠痛阈的升高［1］，但是T型钙通道各个亚型在神经病理性疼痛中的作用目前尚无定论。Cav3.3是T型钙通道的一种亚型，本实验通过建立大鼠背根节慢性压迫痛模型，应用行为学观察的方法，探讨Cav3.3亚型在神经病理痛中的作用。