脊髓ERK活化在瑞芬太尼引起的大鼠痛觉过敏中的作用

The role of activation of ERK in spinal cord on remifentanil-induced hyperalgesia in rats

目的:探讨大鼠脊髓ERK活化在瑞芬太尼引起痛觉过敏中的作用.方法:选择雄性SD大鼠32只,随机分为4组.对照组(n=8,C组):鞘内注射PBS液20μL,30 min后,静脉注入生理盐水1.5 m L·h^(-1),持续4 h;瑞芬太尼加PBS液组(n=8,R+P组):鞘内注射PBS液30 min后,泵入瑞芬太尼;瑞芬太尼加二甲基亚砜(dimethyl sulfoxide,DMSO)组(n=8,R+D组):鞘内注射DMSO 10μL,静脉泵注瑞芬太尼;瑞芬太尼加U1026组(n=8,R+U组):鞘内注射U1026 10μL、PBS液10μL冲管30 min后,泵入瑞芬太尼.瑞芬太尼注射速度1μg·min^(-1)·kg^(-1),注射4 h.分别于术前(T0)、鞘内给药前(Tc)、停药后0.5 h、1 h、2 h及24 h(分别为T1~T4)不同时点测定右足的机械性痛觉阈值.雄性SD大鼠16只,按上述分组方法随机分为4组,每组4只.每组在停药2 h后,取脊髓,应用免疫组化方法观察脊髓p-ERK阳性细胞数目.结果:R+P组、R+D组、R+U组在停药后0.5 h、1 h和2 h机械性痛阈值较术前及C组基础痛阈值显著降低(P<0.001),停药后1 h痛阈值降至最低(P<0.001),术后24 h恢复至基础水平.R+P组、R+D组及R+U组组间痛阈值比较,差异无统计学意义(P>0.05).大鼠脊髓p-ERK阳性细胞数四组间比较,差异无统计学意义(P>0.05).结论:大鼠持续输注瑞芬太尼4 h后痛觉敏感性增加,与脊髓ERK活化可能无关.

AIM： To evaluate the role of activation of ERK in spinal cord on remifentanil-induced hyperalgesia in rats. METHODS： Thirty-two adult male Sprague-Dawley rats were randomly divided into 4 groups,with 8 rats in each group. C group was given intravenous injection of normal saline（ 1.5 m L·h^-1） after intrathecal injection of PBS solution（ 20 μL） for 4 h. R＋P group was given injection of remifentanil（ 1 μg·min^-1·kg^-1） for 4 h after intrathecal injection of PBS solution（ 20 μL）. R ＋ D group was given intravenous injection of remifentanil after intrathecal injection of DMSO solution（ 10 μL）. R＋U group was given continuous intravenous injection of remifentanil（ 1 μg · min^-1·kg^-1）for 4 h after intrathecal injection of U1026 solution（ 10 μL）. The mechanical hyperalgesia threshold was evaluated by the paw pressure test before venipuncture（ T0）,before administration（ Tc）,0.5 h,1 h,2 h and 24 h after drug withdrawal（ T1 ~ T4,respectively）. The p-ERK positive cells in spinal cord were examined after drug withdrawal 1 h with immunohistochemistry. RESULTS：At 0. 5 h,1 h,2 h after drug withdrawal,the paw-pressure threshold of R＋P group,R＋D group and R＋U group were significantly decreased compared with those of C group and baseline（ P〈0.001）. The mechanical pain threshold of R＋P group,R＋D group and R＋U group were minimized after drug withdrawal 1 h.There were no significant differences of the paw-pressure threshold in 24 h after treatment among four groups. There were no statistically significant differences on the numbers of p-ERK positive cells in rat spinal cord among four groups（ P〉0.05）. CONCLUSION： The sensitivity to pain of rats was increased after continuous intravenous injection of remifentanil for 4 h,therefore activa-tion of ERK in spinal cord may be unrelated to remifentanil-induced hyperalgesia.