论文部分内容阅读
目的观察神经病理性疼痛大鼠鞘内注射p38丝裂原活化蛋白激酶(p38MAPK)抑制剂 SB203580的镇痛作用,探讨p38MAPK信号转导通路在慢性神经病理性疼痛中的作用。方法雄性 SD大鼠,体重220-250 g,建立坐骨神经结扎性损伤(CCI)疼痛模型,第一部分 40只CCI大鼠,随机分为5组,对照组、SB0．1μg组、SB0．5μg组、SB2．5μg组和SB5μg组,(n=8),CCI后7 d,鞘内注射2％二甲基亚砜或不同剂量的SB203580(0．1、0．5、2．5、5μg)10μl,在给药前和给药后0．5、3、6、12、24 h用 von Frey丝测定大鼠术侧后爪机械缩足反射阈值(MWT);另外36只大鼠,随机分为6组(n=6):Sham 组、CCI组、DMSO组、SB0．1、0．5、5μg组,CCI后7 d鞘内注射相应剂量SB203580 10μl,给药后6h取L4,5 脊髓,用免疫组织化学方法检测脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白(pcREB)的表达。结果 CCI后大鼠产生了机械痛敏,鞘内注射SB203580剂量依赖性地提高了MWT。CCI后脊髓背角 pCREB阳性神经元增加,鞘内注射SB 0．5、5μg抑制了CCI引起的脊髓背角pCREB表达增加(P< 0．01)。结论鞘内注射SB203580能减轻CCI引起的痛敏,抑制脊髓背角CREB的磷酸化,p38MAPK 信号通路参与慢性神经病理性疼痛。
Objective To investigate the analgesic effect of intrathecal p38 mitogen-activated protein kinase (p38MAPK) inhibitor SB203580 in rats with neuropathic pain and to explore the role of p38 MAPK signal transduction pathway in chronic neuropathic pain. Methods Male Sprague-Dawley rats weighing 220-250 g were used to establish sciatic nerve crush injury (CCI) model. The first part of 40 CCI rats were randomly divided into 5 groups: control group, SB0.1μg group, SB0.5μg group, SB2.5μg group and SB5μg group (n = 8), 7d after CCI, intrathecal injection of 2% dimethyl sulfoxide or different doses of SB203580 (0.1,0.5,2.5,5μg) 10μl , The mechanical contracting threshold (MWT) of the hindpaw was measured by von Frey filaments before administration and at 0.5, 3, 6, 12 and 24 h after administration. Another 36 rats were randomly divided into The rats in Sham group, CCI group, DMSO group, SB0.1, 0.5, 5μg group were injected intrathecally with SB203580 10μl after 7 days of CCI, The expression of phosphorylated cyclic adenosine monophosphate response element binding protein (pcREB) in spinal dorsal horn was detected by immunohistochemistry. Results The rats developed mechanical hyperalgesia after CCI. Intrathecal injection of SB203580 increased MWT dose-dependently. After CCI, pCREB positive neurons increased in spinal dorsal horn. Intrathecal injection of SB 0.5 and 5μg inhibited the expression of pCREB in spinal dorsal horn induced by CCI (P <0.01). Conclusion Intrathecal injection of SB203580 can reduce the pain sensitivity induced by CCI, inhibit the phosphorylation of CREB in spinal dorsal horn, and p38MAPK signaling pathway participates in chronic neuropathic pain.