鞘内联合应用吗啡和氯胺酮对神经痛大鼠脊髓P物质表达的影响

Effect of intrathecal morphine and ketamine on substance P expression in the dorsal horn of neuropathic rats

目的研究鞘内联合应用吗啡和氯胺酮对神经痛大鼠脊髓P物质表达的影响。方法12只Wistar大鼠,体质量220~260 g,制备坐骨神经结扎模型并鞘内置管,随机分为4组(n=3):B组为空白对照组;C组鞘内注射生理盐水10μL;M组鞘内注射吗啡20μg;KM组鞘内注射吗啡10μg和氯胺酮25μg。坐骨神经结扎术后第4天开始鞘内给药,1次/d,连续7 d。用药7 d后处死大鼠,取腰段脊髓,免疫组化法测定脊髓P物质的含量。结果C组P物质表达明显低于B组(P<0.05)和KM组(P<0.01);KM组P物质表达明显高于M组(P<0.05)。结论鞘内联合应用吗啡和氯胺酮的抗伤害性作用,可能与其增加脊髓背角P物质的含量有关;脊髓背角P物质含量减少,可能介导慢性坐骨神经损伤后的痛敏持续状态。

Objective To study the effect of intrathecal morphine and ketarnine on substance P（SP） immuno- histochemical staining in the dorsal horn of neuropathic rats. Methods 12 wistar rats weighing 220 - 260 g were pre- pared for placing loosely constrictive ligatures around the common sciatic nerves, and intrathecal implantation of a cath- eter. The rats were randomly allocated into four groups （ n = 3 ） ： group B （ vehicle, no drugs available ） , group C （ saline 10 I^L） ,group M（morphine 20 p.g） ,group KM（morphine 10 p.g and ketamine 25 ~g）. Morphine and ketamine were administrated intrathecally once a day for 7 days on the forth day after operation 7 days later,the rats were decapitated and the lumbar spinal cord were removed. SP in spinal cord were measured by immunohistochemistry. Results Immnu- nostaining density of SP in group C decreased compared with group B （ P 〈 0. 05 ） and group KM（ P 〈 0. 01 ）. SP stai- ning density in group KM was significantly higher than that in group M（ P 〈 0. 01 ）. Conclusion The antinoeiceptive mechanism of intrathecal morphine and ketamine was related to the increase of SP staining in lumbar spinal cord, how- ever decrease of SP in spinal cord may mediate pain sensitivity after chronic sciatic nerve injury.