布托啡诺对福尔马林致痛大鼠脊髓Fos蛋白表达的影响

Effects of butorphanol on Fos protein expression in spinal cord in a rat model of formalin-induced pain

目的探讨布托啡诺对福尔马林致痛大鼠脊髓Fos蛋白表达的影响。方法SD大鼠25只，随机分为5组（n=5）：生理盐水组（NS组）、福尔马林组（F组）、芬太尼-福尔马林组（FF组）、布托啡诺-福尔马林I组（BF．组）和布托啡诺-福尔马林Ⅱ组（BR组）。NS组和F组腹腔注射0．9％生理盐水500μ，FF组、BR组和BF2组分别腹腔注射0．1mg／kg芬太尼、1mg／kg布托啡诺和2mg／kg布托啡诺，药物均用生理盐水稀释至500-，5min后Ns组右侧后肢跖部皮下注射生理盐水150μl，其余各组均注射4％福尔马林150μl。于注射福尔马林后5、10、20、30、45、60、90、120min时记录痛行为学评分；注射布托啡诺后2h时处死大鼠，取L～k段脊髓，采用免疫组化法测定脊髓Fos蛋白表达水平。结果与NS组比较，其余各组痛行为学评分升高，脊髓Fos蛋白表达上调（P〈0．05）；与F组比较，FF组、BF1组和BF2组痛行为学评分降低，脊髓Fos蛋白表达下调（P〈0．05）；与FF组比较，BF1组痛行为学评分升高，脊髓Fos蛋白表达上调（P〈0．05），BF1组差异无统计学意义（P〉0．05）；与BFI组比较，BR组痛行为学评分降低，脊髓Fos蛋白表达下调（P〈O．05）。结论布托啡诺可减轻大鼠福尔马林致痛程度，其机制与抑制脊髓Fos蛋白表达上调有关，其效应呈剂量依赖性。

Objective To investigate the effects of butorphanol on Fos protein expression in spinal cord in a rat model of formalin-induced pain. Methods Twenty-five SD rats of both sexes aged 8-10 weeks weighing 190- 210 g were randomly divided into 5 groups （n = 5 each）： group Ⅰ intraplantar normal saline （NS）; group Ⅱ intraplantar fomaliu （F） ; group Ⅲ fentanyl ＋ intraplantar formalin （FF） ; group Ⅳ butorphenol 1 ＋ intraplantar formalin （ BFL ） and group V butorphenol 2 ＋ intraplantar formalin （ BF2 ）. In groupⅡ - Ⅴ pain was induced by intraplantar injection of 4% formalin 150 μl in right hindpaw. Fentanyl 0.1 mg/kg, butorphanol 1 mg/kg and butorphanol 2 mg/kg in 500 μl NS were injected intraperitoneally （IP） 5 min before intraplantar formalin injection. In group I normal saline 150 μl was injected into the plantar surface instead of 4% formalin. In group I and normal saline 500μl was injected IP instead of fentanyl or butorphanol. Pain behavior was assessed and scored （0 = normal, no pain, 5 = worst pain, the animal showing flinches and licking） at 5, 10, 20, 30, 45, 60, 90, 120 min following intraplantar formalin injection. The animals were then sacrificed and the lumbar segment （ L35 ） of the spinal cord was obtained for determination of Fos expression in the spinal cord. Results The pain scores and Fos expression in the spinal cord were significantly higher in group F, FF, BF1 and BF2 （ Ⅱ-Ⅴ ） than in NS group （ Ⅰ ） . Intraperitoueal butorphanol significantly reduced pain scores and Fos expression in the spinal cord increased by intraplantar injection of 4% formalin, as intraperitoneal fentanyl did. Conclusion Butorphanol can attenuate intraplantar injection of fonnalin-induced pain in a dose-dependent manner by inhibiting up-regalation of Fos protein in the spinal cord.