宁猛?郑镇伟?蒋珊?游志坚

[摘要] 目的 研究鞘内注射美洛昔康（Mel）对CCI模型疼痛治疗效果和背根神经节（DRG）内生长相关蛋白-43（GAP-43）、神经生长因子（NGF）表达的影响。 方法 成年SD雄性大鼠随机分成四组：正常对照（C）组不做处理，CCI组不予注药，生理盐水（NS）治疗组予注射生理盐水，美洛昔康治疗（Mel）组予注射不同剂量美洛昔康（Mel组100μg，qd、Mel2组200μg，qd、Mel3组100μg，bid、Mel4组200μg，bid）；每（亚）组均为5只大鼠。35只大鼠分别于术前及术后3d、7d测试机械性缩足反射阈值（MWT）和热缩腿潜伏期（TWL）。术后7d取材大鼠DRG，检测其GAP-43、NGF表达水平。 结果 MWT、TWL方面CCI组、NS组和Mel组较正常组显著下降（P<0.05）；美洛昔康组比CCI、NS组下降幅度小（P<0.05），且剂量越大MWT、TWL下降幅度越小（P<0.05）。GAP-43、NGF表达方面CCI组、NS组>Mel组>C组（P<0.05），且美洛昔康剂量越大，表达越少。 结论 鞘内注射美洛昔康能明显减轻大鼠CCI模型的机械痛敏和热痛敏，并降低DRG内GAP-43、NGF的表达水平。

[关键词] 神经性疼痛；鞘内给药；环氧化酶抑制剂；生长相关蛋白-43；神经生长因子

[中图分类号] R614 [文献标识码] A [文章编号] 2095-0616（2017）05-09-06

[Abstract] Objective To study the impact of intrathecal injection of meloxicam to the effect of CCI model on pain management and the expression of Growth-associated protein 43 and Nerve growth factor. Methods Adult SD male rats were randomly divided into four groups.Rats in control group were nothing，rats in CCI group were treated with no drug injection and normal saline，rats in treatment group were treated with saline injection，and rats in meloxicam group were treated with injection of different doses of meloxicam （100μg， qd in Mel1 group，200μg qd in Mel2 group，100μg， bid in Mel3 group，and 200μg， bid in Mel4 group）.5 rats were in each group.Mechanical withdrawal threshold （MWT） and Thermal withdrawal latency （TWL） of the 35 rats were determined before the operation and 3d，7d after the operation.DRG was selected on 7d after the operation to detect the expression level of GAP-43 and NGF. Results MWT and TWL in CCI group，MS group and Mel group were significantly decreased，compared with control group （P<0.05）.The decrease range of Mel group was less than that of CCI group and NS group （P<0.05）. The larger the dose，the smaller the decrease of MWT and TWL （P<0.05）.In the expression level of GAP-43 and NGF，CCI group>NS group>Mel group>Control group （P<0.05）.The larger the Meloxicam dose，the less the expression. Conclusion Intrathecal injection of meloxicam can significantly reduce mechanical allodynia and thermal hyperalgesia of rats CCI model，and reduce the expression of GAP-33 and NGF in DRG.

[Key words] Neuropathic pain；Intrathecal administration；Cyclooxygenase inhibitor；Growth-associated protein 43；Nerve growth factor

神經病理性疼痛（neuropathic pain，NP）是各种疾患引起的外周或中枢神经系统传导通路异常或功能障碍导致的痛敏症状，可出现于许多神经系统疾病中，影响到6%～8%的普通人群。NP对生活质量、情绪和睡眠的影响超过了其致病的病理负担[1]。由于其发病机制尚不明了，治疗效果不满意，目前多采用对症处理。研究[2-3]表明，环氧化酶（cyclooxygenase，COX）与神经性疼痛的发生密切相关，应用COX抑制剂治疗神经疼痛有一定效果。但全身用药带来的副作用却限制了其临床应用，而鞘内给药报道不多。GAP-43被认为是神经损伤生长发育和损伤再生分子标志，NGF表达与DRG出芽有关。二者被认为与神经损伤后神经性疼痛的发生相关[4]。为此，2016年5～10月本研究探讨鞘内注射（intrathecal injection，INTRA）选择性COX抑制剂美洛昔康对CCI疼痛模型的治疗效果，以及对GAP-43、NGF表达水平影响。进……