鞘内注射Cav3.3反义寡聚核苷酸对CCD大鼠痛阈的影响

Pain threshold in CCD rat following intrathecal administration Cav3.3 anti-sence oligonucleotide

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4d每天两次鞘内分别注射Cav3.3-AS、Cav3.3-MM12.5μg/10μl或NS10μl,行为学部分分别观察术后1、3、5、7、10、14d大鼠机械缩足阈值(mechanica lwithdrawal 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10d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。

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.