脊髓磷酸化胞外信号调节蛋白激酶在大鼠切口痛痛觉过敏中的作用

Roles of phosphorylated extracellular signal-regulated kinase in rats with incisional hyperalgesia

目的 研究切口痛模型大鼠脊髓磷酸化胞外信号调节蛋白激酶（p-ERK）表达的变化及鞘内注射ERK上游激酶MEK的抑制剂U0126对其机械性痛觉阈值的影响.方法 雄性SD大鼠32只按随机数字表法分为假手术组、模型组、DMSO组、U0126组,每组8只,前2组大鼠鞘内注射生理盐水20μL;后2组大鼠分别鞘内注射DMSO、U0126 10μL后用生理盐水10μL冲管.注药10min后除假手术组外,后3组大鼠均制备右后足趾部切口痛模型.分别于制作模型前、模型后2、24、48 h应用YLS-3E电子压痛仪测定各组大鼠右足的机械性痛觉阈值.另取SD大鼠24只.分组方法 和处理同上,每组6只.每组分别在模型后2h、24h选择3只应用免疫组化染色检测大鼠脊髓背角p-ERK的表达.结果模型组、DMSO组大鼠模型后2、24、48 h及U0126组大鼠模型后2、24 h有足机械性痛觉阈值均低于模型前,差异有统计学意义（P〈0.05）;DMSO组和模型组之间比较大鼠机械性痛觉阈值差异无统计学意义（P〉0.05）;与同一时间点DMSO组和模型组比较,U0126组大鼠模型后2、24、48 h右足机械性痛觉阈值均增高,差异有统计学意义（P〈0.05）.免疫组化染色结果发现.与假手术组比较模型组和DMSO组模型后2、24 h患侧脊髓背角P-ERK免疫阳性细胞增多;与模型组和DMSO组同一时间比较,U0126组患侧脊髓背角p-ERK阳性细胞减少,差异均有统计学意义（P〈O.05）.结论 鞘内注射U0126可缓解大鼠切口痛痛觉过敏,减少切口痛大鼠脊髓背角P-ERK阳性细胞的表达,说明脊髓背角ERK通路参与大鼠切口痛痛觉过敏的形成.

Objective To investigate the changes of phosphorylated extracellular signal-regulated kinase （p-ERK） expression in the immunoreactive cells of the spinal dorsal hom after plantar incision,and explore the effects of intrathecal administration of MEK inhibitor U0126 on physiological pain threshold in rat models with incisional pain.Methods Thirty-two male SD rats were equally randomized into control group （C group）,incisional pain group （I group）,intrathecal U0126 group （Ugroup） and intrathecal DMSO group （D group）.Twenty-μL physiological saline was injected into the rats of the C group and I group,respectively.Ten-μL DMSO and U0126 were injected into the rats in the U group and D group,respectively.Rat models with incisionai pain were induced in the other 3 groups except the C group.Mechanical hyperalgesia were evaluated by paw-pressure before and 2,24 h and 2 d after the inducement.Another 24 rats were treated as the above method and equally divided into 4 groups; the numbers of p-ERK immunoreactive cells in the dorsal horn were quantified to determine the ERK activation 2 and 24 after the model inducement.Results The paw-pressure threshold in I group and D group 2 and 24 h,and 2 d after the incision,and that in U group 2 and 24 h after the incision were significantly decreased as compared with that in C group （P〈0.05）; that between I group and D group showed no significant difference （P〉0.05）; that in the U group was obviously higher than that in the I group and D group at the same time points （P〈0.05）.Significantly increased numbers of p-ERK immunoreactive cells in the I group and D group were observed as compared with those in the C group （P〈0.05）; those in the U group was obviously decreased as compared with those in the I group and D group at the same time points （P〈0.05）.Conclusion Plantar incision-induced mechanical hyperalgesia can be prevented by intrathecal injection of U0126 through decreasing the expression of p-ERK positive cells,indicating that ERK pathway in the spinal dorsal horn involves in the incision-induced mechanical hyperalgesia in rats.