鞘内注射醋酸泼尼松龙对背根节压迫大鼠的镇痛作用及其机制的探讨

HYPERALGESIA INHIBITION AND POSSIBLE MECHANISM OF INTRATHECAL INJECTION PREDNISOLONE ACETATE IN CHRONIC COMPRESSION OF DORSAL ROOT GANGLIA RATS

目的:研究鞘内注射醋酸泼尼松龙(PA)对背根节慢性压迫(CCD)大鼠痛阈和脊髓背角nNOS表达的影响及其镇痛机制。方法:鞘内置管手术成功雄性SD大鼠100只,随机分为7天组和15天组两组,每组再随机分为假手术(Sham)组,人工脑脊液(ACSF)组,鞘内注射PA0.5、1.0、2.0mg/kg组(n=10)。分别于CCD术前(0)及术后1,3,5,7,9,11,13,15天采用von Frey纤毛机械刺激法和热辐射刺激法评定大鼠机械刺激缩足反射阈值(PWMT)和热刺激缩足反射潜伏期(PWTL);术后第7天和第15天运用免疫组织化学法和Western blot法观察脊髓背角nNOS表达的变化。结果:与术前基础阈值相比,除假手术组外,CCD术后各组的PWMT和PWTL均出现明显地下降(P<0.01),各组间无明显差异(P>0.05)。术后第5天开始,PA2.0mg/kg组与ACSF组相比,PWMT和PWTL显著升高(P<0.05)。免疫组织化学方面,背根节压迫后第7和第15天,ACSF组与PA0.5、1.0mg/kg组脊髓背角阳性神经元数量明显增多,三组之间比较无显著差异(P>0.05)。PA2.0mg/kg组和ACSF相比,第7天和第15天均显著降低(P<0.01)。脊髓背角Western blot检测与免疫组织化学的结果基本一致。结论:鞘内注射PA有镇痛作用,其作用机制可能与抑制脊髓背角nNOS的表达有关。

Objective： To study the effects of intrathecal injection prednisolone acetate （PA） on nociceptive stimulus and neuronal nitric oxide synthase （nNOS） expression in spinal cord of chronic compression of dorsal root ganglia （CCD） rats. Methods： 100 SD rats with intrathecal catheter insertion were divided into 7th and 15th day groups. Each group includes sham group, artificial cerebral spinal fluid （ACSF） group, PA 0.5, 1.0 and 2.0 mg/kg groups（n = 10）. Paw withdrawal mechanical threshold （PWMT） and paw withdrawal thermal latency （PWTL） were measured on 0,1,3,5,7,9,11, 13,15 days after operation. Immunohistochemical and Western blot techniques were taken to evaluate changes of nNOS expression in spinal cord. Results： Compared with basic pain threshold, all groups except sham groups exhibited a significant reduction on injured side in PWML and PWTL（P 〈 0.01 ） after operation. There was no significant difference among these groups （ P 〉 0. 0 5 ） . From 5 th day after CCD operation , there was significant difference between PA 2.0 mg/kg and ACSF group（P 〈 0.05）. On 7th day and 15th day, immunohistochemistry manifested obvious increasement in nNOS-positive neurons in the superficial dorsal horn of ACSF group, PA 0.5 mg/kg group and 1.0mg/kg group, no significant difference was showed among these groups （ P 〉 0.05 ）. The nNOS-positive neurons in the superficial dorsal horn were significantly decreased in PA 2.0 mg/kg group compared with ACSF group on both 7th day and 15th day（P 〈0. 01 ）. The results of western blot were similar to immunohistochemistry. Conclusion ： It is suggested that intrathecal administration of PA inhibited hyperalgesia of rats induced by CCD. The inhibition of neuronal nitric oxide synthase in rat spinal cord may partly involved in this process.