鞘内注射布托啡诺对福尔马林诱导大鼠脊髓背角NMDAR的影响

The effects of intrathecal Butorphanol on changes of neuronal NMDAR expression in spinal dorsal horn in rats with formalin-induced inflammatory pain

目的观察鞘内注射布托啡诺对福尔马林炎性痛大鼠脊髓背角N-甲基-D-天冬氨受体（NMDAR）表达的影响。方法健康雄性SD大鼠20只，体重220～280g。随机分为4组（n=5）：对照组（C组），鞘内注射生理盐水组（N组），鞘内注射12．5μg布托啡诺组（B1组），鞘内注射25μg布托啡诺组（B2组）。在大鼠的左后足掌面皮下注射5％福尔马林50μl致痛前30min，N组、B1组和B2组分别注射生理盐水、12．5μg布托啡诺、25μg布托啡诺，C组在福尔马林注射前不注射任何试剂。记录福尔马林诱导出注射后爪的双相理毛行为时间（在福尔马林注射后第1时相，0—5min；第2时相，10—60min）。所有大鼠均在注射后2h处死，用免疫组化法测定大鼠L5节段脊髓背角NMDA受体的表达。结果与C组相比，N组和B1组对福尔马林诱导的第1和2时相．影响差异无统计学意义（P〉0．05），3组脊髓背角NMDA受体表达均增加，相比较差异无统计学意义（P〉0．05）。与C组比较，B2组引起第1和2时相的后爪理毛行为的总计反应时间明显减少，并显著降低福尔马林致痛大鼠L5脊髓背角NMDA受体表达（P〈0．05）。结论鞘内注射布托啡诺能够对福尔马林诱导的疼痛行为产生明显的抑制作用，并具有剂量依赖性，其镇痛机制与通过抑制NMDA受体激活产生有关。

Objectives To investigate the effects of intrathecal Butorphanol on changes of neuronal NMDAR expression in spinal dorsal horn in rats with formalin-induced inflammatory pain. Methods Twenty healthy male Sprague-Dawley rats （220 -280g） were randomly divided into four groups（ n =5） ： Control group （group C） , intrathecal saline group （group N）, 12.5μg butorphanol group （group B1 ） and 25 μg butorphanol group （group B2 ） at 30 min before the subcutaneous formalin injection into the left hind paw. The control group （ group C ） of rats received no agent prior to being injected with formalin. After injection, the formalin-induced behaviors were continuously recorded for 60 min by an experienced observer. Rats were killed 2 h after the formalin injection. And the fifth lumbar spinal cord was dissected, and the expression of NMDA receptors Was determined by immunohistology. Results 25 μg butorphanol （ group B2） were capable of inhibiting both phases of formalin response. However, other groups did not significantly affect the expression of both early and late phases. Intrathecal with 25μg hutorphanol （ group B2） were enough to decrease the expression of spinal cord NMDA receptors. Conclusion The results provided evidence that the intrathecal butorphanol could produce a dose-dependent antinociception in a rat model of formalin- induced inflammatory pain. The mechanisms of analgesia may be that butorphanol can suppress the stimulation of NMDA receptors.