Lidocaine suppresses the increased extracellular signal-regulated kinase/cyclic AMP response element-binding protein pathway and pro-inflammatory cytokines in a neuropathic pain model of rats
Lidocaine suppresses the increased extracellular signal-regulated kinase/cyclic AMP response element-binding protein pathway and pro-inflammatory cytokines in a neuropathic pain model of rats
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DOI：
10.1097/eja.0b013e32834050fb
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发表时间：
2011-02-01
影响因子：
3.6
通讯作者：
Jeon, Yeon S.
中科院分区：
文献类型：
--
作者：
Joo, Jin D.;Choi, Jin W.;Jeon, Yeon S.
背景与目的脊髓神经结扎术(SNL)后，细胞外信号调节蛋白1/2(ERK 1/2)和环磷酸腺苷反应元件结合蛋白(CREB)的表达增加。方法24只雄性SD大鼠随机分为3组，每组8只：假手术组(对照组)、神经病理性疼痛+生理盐水组(NP+NS)、神经病理性疼痛+利多卡因组(NP+Lido，2mgkg(-1)h(-1))。麻醉大鼠左侧L5和L6 SNL。在SNL后7d和植入泵(生理盐水或利多卡因)后连续7d进行机械戒断阈值测试。在植入后第7天，取其大脑和脊髓。用免疫印迹和逆转录聚合酶链式反应检测ERK 1/2、CREB蛋白和促炎性细胞因子(肿瘤坏死因子a、细胞间黏附分子1、单核细胞趋化蛋白1和巨噬细胞炎性蛋白2)的表达。仅在脊髓组织中，NP+LIDO组ERK1/2和CREB蛋白表达显著降低至39%，与NP+NS组相比分别降低48%。NP+利多组与NP+NS组比较，促炎细胞因子的表达明显减少(P
Background and objective Rats which have undergone spinal nerve ligation (SNL) display increases in the expression of extracellular signal-regulated kinase (ERK 1/2) and cyclic AMP response element-binding (CREB) protein. The present study was designed to determine whether lidocaine has a beneficial effect on the treatment of neuropathic pain by analysing related proteins.Methods Twenty-four male Sprague-Dawley rats were randomly allocated to three groups (eight per group): sham-operated (control) group, a neuropathic pain and normal saline group (NP+NS), a neuropathic pain and lidocaine group (NP+Lido, 2mgkg(-1) h(-1)). Anaesthetised rats received left L5 and L6 SNL. The mechanical withdrawal threshold test was performed 7 days after SNL and for 7 days with the pump implanted (saline or lidocaine). At post-implanted pump day 7, their brains and spinal cords were harvested. ERK 1/2, CREB proteins and mRNA amounts of pro-inflammatory cytokines (tumour necrosis factor a, intercellular adhesion molecule 1, monocyte chemo-attractive protein 1 and macrophage inflammatory protein 2) were assessed by immunoblotting or reverse transcriptase-PCR on samples collected from the three groups.Results Lidocaine increased the mechanical withdrawal threshold of a neuropathic rats. In only spinal tissues, ERK 1/2 and CREB proteins in the NP+Lido group was significantly reduced to 39%, and 48% in comparison with the NP+NS group. The NP+Lido group showed a significant reduction in mRNA amounts of pro-inflammatory cytokines compared with the NP+NS group (P