鞘内注射米贝地尔抑制慢性坐骨神经结扎大鼠机械痛敏和热痛敏

MIBEFRADIL ADMINISTERED INTRATHECALLY INHIBITS MECHANICAL AND HEAT HYPERALGESIA FOLLOWING CHRONIC CONSTRICTION INJURY(CCI) OF THE SCIATIC NERVE IN RATS

目的:观察脊髓水平T型钙通道阻滞剂米贝地尔(m ibefrad il)对坐骨神经慢性松结扎(CCI)大鼠机械和热痛阈的影响,探讨脊髓T型钙通道在伤害性信息传递中的作用。方法雄性SD大鼠48只,随机分为6组(n=8):假手术组(Sham),CCI组,CCI+生理盐水组,CCI+米贝地尔50μg、100μg、200μg组。CCI组和Sham组在术前、术后1 d、3 d、5 d、7 d、14 d、21d测定大鼠机械缩腿阈值(MWT)和热缩腿潜伏期(TWL);其余各组大鼠在手术前5天先进行鞘内置管,在术前测定基础MWT和TWL,CCI手术后5 d鞘内注射不同剂量的米贝地尔,测定给药前、给药后0.5 h、1 h、2 h、4h、8 h大鼠MWL和TWL。结果:CCI组从术后3 d开始直到本实验观察的术后21 d,MWT和TWL均明显降低,与Sham组相比具有显著性意义(P<0.01);CCI加生理盐水组大鼠在各个时间点上与给药前相比MWT和TWL无明显改变(P>0.05);CCI加米贝地尔各个剂量组大鼠在给药后MWT和TWL均逐渐增加,具有剂量依赖性,并随时间的延长又逐渐恢复到给药前水平,CCI+米贝地尔200μg在给药后1 h时作用最明显,与给药前和盐水组相比P<0.01,并一直持续到给药后4h。结论:鞘内注射米贝地尔能明显减轻慢性坐骨神经松结扎大鼠机械痛敏和热痛敏,提示T型钙通道在脊髓水平参与疼痛信息传递。

Objective：By observing the effect of mibefradil administered intrathecally on the mechanical and heat hyperalgesia following chronic constriction injury（CCI） of the sciatic nerve in rats,this study evaluates the role of T-type calcium channel in nociceptive transmission at the spinal level. Methods ： Forty eight male Sprague-Dawley rats weighting 230 -250g were randomly divided into six groups （n = 8 ） ： Sham operation,CCI,CCI ＋0.9% saline,CCI ＋ mibefradil 50 μg,CCI ＋ mibefradil 100 μg,CCI ＋ mibe- fradil 200 μg group. The mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） in sham or CCI group were measured before operation and 1,3,5,7,14 and 21 days after operation, respectively. The other groups were intrathecally cathetered at 5 d before operation ; mibefradil or saline were administered intrathecally after CCI 5 d. The nociceptive thresholds were measured before and after administration 0.5,1,2,4 and 8h respectively. Results ： CCI group formed steady mechanical and heat hyperalgeia from the 3th day after operation. Mibefradil of 50μg, 100μg,200μg administered intrathecally can increase the MWT and TWL in a dose-dependent pattern. Eight hours after administration, the nociceptive threshold of each group returned to the pre-drug level. The effect of the 200μg group at lh after administration was the strongest and lasted to 4h. Conclusion： Mibefradil administered intrathecaUy could reduce the mechanical and heat hyperalgesia of rats following CCI. T-type calcium channel may have a role in nociceptive transmission at the spinal level.