论文部分内容阅读
目的探讨鞘内注射NaV 1．8反义寡核苷酸对慢性神经病理性疼痛大鼠的镇痛作用。方法雄性SD大鼠24只,随机分为4组(n=6):Ⅰ组(CCI+生理盐水组);Ⅱ组(CCI+Nay1．8错义寡核苷酸45μg组);Ⅲ组(CCI+NaV 1．8反义寡核苷酸45μg组);Ⅳ组(CCI+NaV 1．8反义寡核苷酸90 μg组)。按Bennett法制作CCI模型,CCI 5d鞘内置管,CCI 8 d开始鞘内给药,每日给药2次,连续5d。于CCI前2d和CCI 1、3、5、7、9、11、13 d测定机械痛阈和热痛阈,CCI 14d取双侧L4-6背根神经节 (DRG),测定钠通道NaV 1．8 mRNA的表达。结果与CCI前2 d前比较,Ⅰ、Ⅱ组在CCI 5-13 d术侧机械痛阈降低,热痛阈缩短;Ⅲ组CCI 5-13 d术侧机械痛阈降低,CCI 3-9 d热痛阈缩短,Ⅳ组CCI 5 -9 d术侧机械痛阈降低,CCI 3-7 d热痛阈缩短(P<0．05或0．01)。与Ⅰ、Ⅱ组比较,Ⅲ、Ⅳ组CCI 11、13 d术侧机械痛阈增加,热痛阈延长(P<0．05或<0．01)。CCI 14 dⅢ、Ⅳ组术侧DRG中NaV 1．8 mRNA表达低于Ⅰ、Ⅱ组(P<0．01),Ⅳ组DRG NaV 1．8 mRNA表达低于Ⅲ组(P<0．01)。结论鞘内注射45、90μg/次NaV 1．8反义寡核苷酸对大鼠神经病理性疼痛有镇痛作用,90μg/次剂量效果较好,其机制是通过下调DRG中NaV 1．8 mRNA钠通道表达实现。
Objective To investigate the analgesic effect of intrathecal NaV 1.8 antisense oligonucleotide on chronic neuropathic pain rats. Methods Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6): group Ⅰ (CCI + saline); group Ⅱ (CCI + Nay1.8 missense oligonucleotide 45μg); group Ⅲ + NaV 1.8 antisense oligonucleotide 45 μg); group Ⅳ (CCI + NaV 1.8 antisense oligonucleotide 90 μg). According to the Bennett method, the CCI model was established. The CCI 5d intrathecal catheter was administered intrathecally on the 8th day of CCI and administered twice daily for 5 days. Mechanical pain thresholds and thermal pain thresholds were measured 2 days before and 1, 3, 5, 7, 9, 11 and 13 days after CCI. L4-6 dorsal root ganglion (DRG) was taken on the 14th day after CCI. NaV 1 .8 mRNA expression. Results Compared with those before 2 days of CCI, the mechanical pain threshold of group Ⅰ and Ⅱ decreased and the thermal pain threshold shortened at 5-13 days after CCI. The mechanical pain threshold at 5-13 days of CCI decreased in group Ⅲ, The thermal pain threshold was shortened. The mechanical pain threshold was decreased on the side of CCI 5-9 d in group Ⅳ, and the thermal pain threshold was shortened 3-7 days after CCI (P <0.05 or 0.01). Compared with group Ⅰ and group Ⅱ, the mechanical pain threshold was increased on the 11th and 13th day in group Ⅲ and group Ⅳ, and the thermal pain threshold was prolonged (P <0.05 or <0.01). The expression of NaV 1.8 mRNA in DRG in group Ⅲ and Ⅳ was lower than that in group Ⅰ and Ⅱ (P <0.01), while the expression of DRG NaV 1.8 mRNA in group Ⅳ was lower than that in group Ⅲ (P <0.01) . Conclusion Intrathecal injection of 45 and 90 μg / dose NaV 1.8 antisense oligonucleotide has an analgesic effect on neuropathic pain in rats. The effect is good at 90 μg / dose. The mechanism is that NaV 1.8 mRNA Sodium channel expression is achieved.