脊髓上水平ERK1/2信号转导通路在小鼠神经病理性痛维持中的作用  

Role of extracellular signal-related kinase 1/2 signal transduction pathway at supraspinal level in maintenance of neuropathic pain in mice

作　　者：苗蓓[1] 殷悦[1] 周田田[1] 邵翠杰[1] 曹君利[1] 陈秋萍[2] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室,221004 [2]南通大学附属医院麻醉科

出　　处：《中华麻醉学杂志》2013年第8期924-927,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金青年基金项目（81200861）;江苏省教育厅“青蓝工程”资助（53041212）;江苏省高校自然科学基金面上项目（09KJB320019）;徐州医学院振兴计划资助课题（53631214）

摘　　要：目的 评价脊髓上水平细胞外信号调节蛋白激酶（ERK） 1/2信号转导通路在小鼠神经病理性痛维持中的作用.方法 健康昆明小鼠64只,雌雄各半,体重18～20 g,2月龄,采用随机数字表法,将其分为4组（n=16）：假手术组（S组）、神经病理性痛组（CCI组）、CCI＋ U0126（丝裂原激活蛋白激酶激酶的抑制剂）组、CCI＋二甲基亚砜（DMSO）组.S组仅暴露坐骨神经但不进行结扎,其余各组采用坐骨神经慢性压迫性损伤（CCI）法制备神经病理性痛模型,CCI术后5d,CCI＋ U0126组和CCI＋ DMSO组分别经侧脑室注射5μg U0126（溶于5％DMSO5μl）及5％DMSO5 μl,注射时间10 s,留针20s.于术前（基础状态）、侧脑室给药前（T1）、侧脑室给药后30 min（T2）、2h（T3）、6h（T4）、12h（T5）、24h（T6）时应用von Frey纤维细丝和热辐射仪测定机械缩足反应阈（MWT）和热缩足反应潜伏期（TWL）.结果 与S组比较,CCI组、CCI＋ DMSO组T1-6时、CCI＋ U0126组T1时MWT降低,TWL缩短（P＜0.05）,CCI＋ U0126组T2-6时MWT和TWL差异无统计学意义（P＞0.05）；与CCI组比较,CCI＋U0126组T2-6时MWT升高,TWL延长（P＜0.05）,CCI＋ DMSO组上述各指标差异无统计学意义（P＞0.05）.结论 脊髓上水平ERK1/2信号转导通路参与了小鼠神经病理性痛的维持.Objective To evaluate the role of extracellular signal-related kinase （ERK） 1/2 signal transduction pathway at the supraspinal level in maintenance of neuropathic pain in mice.Methods Sixty-four Kunming mice,aged 2 months,weighing 18-20 g,were randomly divided into 4 groups （n =16 each）：sham operation group （group S）,chronic constrictive injury （CCI） group; CCI ＋ U0126 （MEK inhibitor） group; CCI ＋ dimethyl sulfoxide （DMSO） group.Neuropathic pain was induced by CCI.The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1mmintervals with 4-0 silk thread in CCI,CCI ＋ U0126 and CCI ＋DMSO groups.On 5 days after CCI,5 μg U0126 （in 5 μl of 5％ DMSO） and 5％ DMSO 5 μl were injected into the lateral cerebral ventricle over 10 s in CCI ＋ U0126 and CCI ＋ DMSO groups,respectively,and the time of.needle retaining was 20 s.Paw withdrawal threshold to mechanical stimulation with yon Frey filament （MWT） and paw withdrawal latency to thermal stimulation （TWL） were measured before operation （baseline）,before intracerebroventricular injection （T1）,and at 30 min and 2,6,12 and 24h after intracerebroventricular injection （T2-6）.Resuits Compared with group S,MWT was significantly decreased and TWL was shortened at T1-6 in CCI and CCI ＋DMSO groups,and at T1 in CCI ＋ U0126 group （P ＜ 0.05）,while no significant change in MWT and TWL was found at T2-6 in group CCI ＋ U0126 （P ＞ 0.05）.Compared with group CCI,MWT was significantly increased and TWL was prolonged at T2-6 in group CCI ＋ U0126 （P ＜ 0.05）,while no significant change in MWT and TWL was found in group CCI ＋ DMSO （P ＞ 0.05）.Conclusion ERK1/2 signaling transduction pathway at the supraspinal level is involved in maintenance of neuropathic pain in mice.

关 键 词：神经痛 细胞外信号调节MAP激酶类 

分 类 号：R741[医药卫生—神经病学与精神病学]