鞘内注射T型钙通道反义寡聚核苷酸对慢性背根节压迫大鼠痛阈的影响

Mechanical and thermal antinociception in rat following intrathecal administration Cav3.0 anti-sence oligonucleotide

目的观察鞘内注射T型钙通道(Cav3.0)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,初步探讨脊髓T型钙通道在神经病理性疼痛形成中的作用。方法鞘内置管♂SD大鼠32只,随机分为4组(n=8):CCD+NS组、CCD+Cav3.0反义寡聚核苷酸组(CCD+Cav3.0-AS)、CCD+Cav3.0错义寡聚核苷酸组(CCD+Cav3.0-MM)、假手术(sham)+NS组。各组大鼠在CCD或sham术后d1始连续4d每天2次鞘内分别注射12.5μg,容积均为10μl的Cav3.0-AS、Cav3.0-MM或NS10μl,分别观察手术后1～14d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Cav3.0反义寡聚核苷酸能延缓CCD大鼠痛敏的形成,在CCD术后d8～9才形成与CCD+NS组类似的痛敏,而鞘内注射Cav3.0错义寡聚核苷酸则与CCD+NS组差异无统计学意义。结论脊髓T型钙通道参与神经病理性疼痛的形成,抑制脊髓T型钙通道基因的表达具有疼痛治疗作用。

Aim To investigate the effect of intrathecal （IT） T type calcium channels （Cav3.0） anti-sence oligonucleotide on the mechanical and thermal hyperalgesia following chronic compression of dorsal root ganglion（CCD）in rats, and try to elucidate the role of T-type calcium channels in the development of the neuropathic pain at spinal level. Methods Thirty two male SD rats after implanted catheter intrathecally were randomly divided into four groups （ n = 8 ） ： CCD ＋ NS groups, CCD ＋ intrathecal administered Cav3.0 antisence oligonucleotide（ CCD ＋ Cav3.0-AS group）, CCD ＋ intrathecal administered Cav3.3 mismatch oligonucleotide （ CCD ＋ Cav3.0-MM group ） , sham ＋ NS group. Rats in every group were intrathecal administered respectively Cav3.0-AS, CCD ＋ Cav3.0-MM twice everyday from postoperative day 1 to day 4 or NS. Measured mechanical withdrawal threshold（MWT） and thermal withdrawal latency（TWL） of rats in every group before operation and postoperative days 1 - 14. Results Cav3.0-AS intrathecal administered could delay the development of hyperalegesia, until postoperative 8-9 day and the MWT and TWL of the rats in Cav3.0-AS group became similar with the CCD ＋ NS group, however, the MWT and TWL of rats in Cav3.0-MM group had no significance difference VS CCD ＋ NS group. Conclusion Cav3.0 T type calcium channel has a key role in the development of the neuropathic pain, and by inhibiting the expression of spinal cord Cav3.0 gene may contribute to the treatment of the neuropathic pain.