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鞘内注射p38 MAPK抑制剂对神经病理性疼痛大鼠脊髓背角脑源性神经营养因子表达的影响
袁红斌,严晓娣,陈前波,周双琼,
0
(第二军医大学长征医院麻醉科,上海 200003)
摘要:
目的 观察鞘内注射p38 MAPK抑制剂SB203580对坐骨神经压缩性损伤(CCI)神经病理性疼痛大鼠的镇痛效果及脊髓背角p38丝裂原活化蛋白激酶(p38 MAPK)、脑源性神经营养因子(BDNF)的表达,探讨大鼠神经病理性疼痛可能的发生机制。 方法 30只SD雄性大鼠随机分为3组(n=10):假手术组、对照组(CCI组)、SB203580组(CCI术前30 min及术后第1~3天鞘内注射SB203580,剂量为0.1 ml/kg)。于CCI术前2 h以及术后第4~14天测定大鼠右足机械痛阈值;术后第14天取损伤侧腰段脊髓,采用免疫组化方法观察脊髓背角p38 MAPK及BDNF的表达。结果 与术前相比,假手术组术后机械痛阈值差异无统计学意义,对照组、SB203580组在CCI术后机械痛阈值明显降低(P<0.05);与假手术组相比,CCI术后,对照组、SB203580组机械痛阈值明显降低(P<0.05);与对照组相比,CCI术后第4~14天SB203580组机械痛阈值明显升高(P<0.05)。与假手术组相比,对照组、SB203580组脊髓背角p38 MAPK表达及BDNF释放明显增加(P<0.05);与对照组相比,SB203580组损伤侧脊髓背角p38 MAPK表达及BDNF释放明显降低(P<0.05)。结论 鞘内注射p38 MAPK抑制剂可能通过降低损伤侧脊髓背角p38 MAPK表达,抑制BDNF释放,从而缓解CCI大鼠慢性神经病理性疼痛。
关键词:  神经病理性疼痛  SB203580  p38丝裂原活化蛋白激酶类  脑源性神经营养因子
DOI:10.3724/SP.J.1008.2010.0883
投稿时间:2010-03-12修订日期:2010-05-13
基金项目:
Influence of intrathecal injection of p38 MAPK inhibitor on BDNF expression in dorsal horn of spinal cord of rats with neuropathic pain
YUAN Hong-bin,YAN Xiao-di, CHEN Qian-bo, ZHOU Shuang-qiong
(Department of Anesthesiology, Changzheng Hospital, Second Military Medical University,Shanghai 200003)
Abstract:
Objective To observe the effect of intrathecal p38 MAPK inhibitor (SB203580) treatment on neuropathic pain and the expression of p38 MAPK and BDNF in dorsal horn of spinal cord in rats with chronic constriction injury (CCI), So as to investigate the possible mechanisms of neuropathic pain. Methods Totally 30 SD rats were evenly randomized into 3 groups (n=10): sham group receiving intrathecal injection of sodium chloride, control group receiving intrathecal injection of sodium chloride and CCI surgery, and SB203580 group receiving intrathecal injection of SB203580 and CCI surgery. SB203580 (0.1 ml/kg) was administered 0.5 h before and 1-14 d after CCI surgery. The mechanical thresholds were tested 24 h before and 4-14 d after CCI surgery. p38 MAPK expression and BDNF release in the dorsal horn were determined using immunohistochemistry method 14 d after CCI surgery. Results The mechanical thresholds in the control and SB203580 groups were significantly lower after CCI surgery compared with that before CCI surgery (P<0.05), but there was no significant change in the control group(P>0.05). Compared with the sham operation group, the mechanical thresholds were significantly lower in the other two groups after CCI surgery (P<0.05). The mechanical threshold of SB203580 group was significantly higher than that of the control group after CCI surgery(P<0.05). The p38 MAPK expression and BDNF release were significantly higher in the control and SB203580 groups compared with those in the sham operation group (P<0.05), and those in the SB203580 group were significantly lower than those in the control group (P<0.05). Conclusion Intrathecal injection of p38 MAPK inhibitor SB203580 can attenuate hyperalgesia in CCI rats through decreasing p38 MAPK expression and BDNF release.
Key words:  neuropathic pain  SB203580  p38 mitogen-activated protein kinases  brain-derived neurotrophic factor