曲马多对切口痛诱发大鼠脊髓背角神经元c-fos基因和血液IL-6表达的抑制作用  

Tramadol inhibits c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats

作　　者：刘甬民[1] 祝胜美[1] 王奎荣[1] 陈庆廉[1] 郑跃英[1] 

机构地区：[1]浙江大学医学院附属第一医院麻醉科,浙江杭州310003

出　　处：《浙江大学学报（医学版）》2009年第4期392-398,共7页Journal of Zhejiang University(Medical Sciences)

摘　　要：目的:在大鼠切口痛模型中研究腹腔注射曲马多对脊髓c-fos蛋白表达和血液IL-6含量的影响。方法:雄性SD大鼠48只,随机分为6组,每组8只,分别为假手术组、切口痛组、术前3个浓度曲马多预处理组(剂量分别为1 mg/kg、10 mg/kg、20 mg/kg)和术后曲马多治疗组(剂量为10mg/kg)。按Brennan法制成大鼠切口痛模型,以von Frey细丝法(机械性痛觉过敏)、热辐射法(热痛觉过敏)和累积疼痛评分法观察疼痛的行为学变化。手术后2 h取脊髓,并以免疫组织化学检测脊髓c-fos表达(Fos蛋白,以FLI阳性神经元表示),ELISA法测定血清IL-6含量。结果:与假手术组比较,在术后2 h时切口痛组大鼠的von Frey纤毛刺激缩爪阈值明显降低(P<0.01),热刺激缩爪潜伏期明显缩短(P<0.01),累积疼痛评分明显升高(P<0.01);与切口痛组比较,曲马多预处理10 mg/kg和20 mg/kg组大鼠的von Frey纤毛刺激缩爪阚值均明显增加(P<0.01),热刺激缩爪潜伏期均明显延长(P<0.01),累积疼痛评分均明显降低(P<0.01),此效应呈剂量依赖性;PT10组大鼠的行为学改变与T10组相似。切口痛组FLI细胞主要分布在~层,曲马多预处理10 mg/kg和20 mg/kg组FLI细胞与切口痛组相比减少。与假手术组比较,切口痛组大鼠脊髓c-fos表达和血液IL-6含量明显增加(P<0.01);与切口痛组比较,曲马多预处理10 mg/kg和20 mg/kg组能使脊髓c-fos表达和血液IL-6含量明显降低(P<0.01),此效应呈剂量依赖性,而术后曲马多治疗组这种抑制作用弱于曲马多预处理10 mg/kg组(P<0.05)。与切口痛组比较,曲马多预处理1 mg/kg组的痛阈和脊髓c-fos表达以及血液IL-6含量差异无显著性意义(P>0.05)。结论:曲马多能对疼痛引起的脊髓灰质背角FLI阳性神经元增多和血液IL-6含量增加的效应产生剂量依赖性的抑制作用,曲马多预处理效果更强;脊髓灰质背角~层可能是曲马多产生痛觉调制的主要部位。在大鼠切口痛模型中,曲马多的Objective： To investigate effect of tramadol on c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats. Methods： The Brennan pain model was induced by incision on the planter surface of left hind paw in rats. Forty-eight rats were randomly divided into six groups ：Sham group （Group C）,control group （Group I ,pretreatment with saline 5 ml）,three tramadol pretreatment groups （Group T1 ,T10 and T20,pretreated with 1 mg/kg, 10 mg/kg and 20 mg/kg tramadol, respectively） and one tramadol treatment group （Group PT10,treated with tramadol 10 mg/kg immediately after operation）. Pain behavior was assessed by withdrawal threshold to von Frey filament stimulation intensity,response latency of the hind paw to radiant thermal and a cumulative pain score 2 h after incision. Fos positive neurons in spinal cord were identified by the immunohistochemieal technique. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay （ELISA）. Results： Withdrawal threshold to von Frey filament stimulation intensity and response latency of the hind paw to radiant thermal in Group I were significantly lower than those in Group C （P^0.01）. Cumulative pain score in Group I was significantly higher than that in Group C （P^0.01）. In Groups of T10 and T20, withdrawal threshold to yon Frey filament stimulation intensity and response latency of the hind paw to radiant thermal were significantly higher than those in Group I （P^0. 01）,cumulative pain score was significantly lower than that in Group I in a dose-dependent manner （P^0.01）, and were also those in Group PT10. The greatest density of Fos positive neurons was located in lamine I - ~ in Group I . Serum IL-6 levels were significantly elevated in Group I . Pretreatment with tramadol showed a dose-depended inhibitory effect on c-fos expression and serum IL-6 production,but not in Group T1. Administration of tramadol postoperatively also suppressed the c fos expression and serum IL-6 production as s

关 键 词：疼痛 手术后/药物疗法 白细胞介素6/血液 曲马朵/投药和剂量 基因 FOS 曲马朵/药理学 脊髓 c—fos IL 6 大鼠 

分 类 号：R96[医药卫生—药理学]