Objective Spinal cord injury-induced neuropathic pain(NP)does not respond well to any existing therapies clinically.This study aimed to explore the molecular metabolisms neuropathic pain by observing the expressions of the N -methyl-D-as-partic acid receptor 2B(NR2B),tumor necrosis factor-alpha(TNF-α)and brain-derived neurotrophic factor(BDNF)in different sta-ges of the condition in SD rats. Methods Thirty-six adult SD rats were randomly divided into a control,a sham operation and an NP model group.The NP model was established by spinal nerve ligation. At 5 and 14 days after modeling,the hindlimb motor function and paw withdrawal threshold(PWT)of the rats were evaluated by the open-field test and the expressions of NR 2B,TNF-αand BDNF in the dor-sal root ganglia of the L4-6 spinal cord were determined by Western blot. Results At 5 days after modeling,the open-field test showed a significantly shorter total distance of movement in the sham operation group than in the control([14 927.93 ±560.87]vs [18 225.15±371.76]mm,P<0.05)and even shorter in the NP model group([3 224.92±89.64]vs[18 225.15±371.76]mm, P<0.01).The time of activity was markedly decreased in the NP model group as compared with that in the control([203.48±19.94]vs [745.95±13.48]s,P<0.01),but with no statistically significant difference between the sham operation and control groups([727.93± 16.29]vs[745.95±13.48]s,P>0.05).At 14 days after modeling,both the total distance of movement and time of activity were re-markably shorter in the NP model than in the sham operation and control groups([3 395.53±96.12]vs[17 382.26±482.31]and [17 975.40±416.56]mm,P<0.01;[195.53±96.12]vs[739.31±18.36]and[775.20±16.84]s, P<0.01).The PWT showed no statistically significant difference among the three groups of rats before modeling(P>0.05)but markedly decreased in the NP model as compared with the sham operation and control groups(P<0.01),with no significant difference between the latter two(P>0.05).The expressions of NR2B,TNF-αand BDNF were remarkably up-regulated in the NP model group in comparison with the sham operation and control groups at 5 days after modeling(P>0.05)and even more significantly at 14 days(P<0.01). Conclusion NR2B and BDNF may be involved in the development and progression of neuropathic pain in rats.%目的 脊髓创伤后引起的神经痛是困扰患者的重要因素,目前临床上尚无有效的治疗方案.通过大鼠L5脊神经结扎(SNL)法建立后肢神经痛模型,观察不同时间点脊髓背根神经节中离子型谷氨酸受体2B亚型(NR2B)以及肿瘤坏死因子-α(TNF-α)、脑源性神经营养因子(BDNF)的表达变化并探讨可能存在的分子作用机制. 方法 36只成年SD雄性大鼠,随机数字表法分成对照组,假手术组和手术组.对照组不做任何处理,手术组建立脊神经结扎模型,假手术组操作同手术组仅不结扎脊神经.通过旷场试验及术侧足跖缩足阈值观察造模前,造模后第5,14天大鼠活动和神经痛情况,免疫蛋白印迹法检测大鼠术侧腰4-6段脊髓背根神经节NR2B及TNF-α和BDNF表达情况. 结果 造模后5 d,与对照组比较,假手术组大鼠总里程略降低[(18225.15±371.76)mm vs(14927.93±560.87)mm,P<0.05],活动时间相比差异无统计学意义(P>0.05);手术组大鼠总路程,活动时间较对照组均显著降低[(18225.15±371.76)mm vs(3224.92±89.64)mm,(727.93±16.29)s vs (203.48±19.94)s,P<0.01].与假手术组比较,手术组大鼠总里程,活动时间显著减少(P<0.01).造模后14 d,与对照组和假手术组比较,手术组大鼠总路程和活动时间明显减少(P<0.01).造模前,3组大鼠 PWT相比差异无统计学意义(P>0.05).造模后5 d和14 d,与对照组及假手术组比较,手术组大鼠术侧PWT均显著降低(P<0.01).假手术组大鼠疼痛阈值未受到明显影响,与对照组相比差异无统计学意义(P>0.05).造模后5 d,假手术组和手术组BDNF、TNF-α和NR2B表达较对照组升高(P<0.05),手术组BDNF、TNF-α和NR2B表达较假手术组升高(P<0.05).造模后14 d,与对照组和假手术组比较,手术组BDNF、TNF-α和NR2B表达升高(P<0.01). 结论 NR2B和BDNF表达可能在参与调节了神经痛的发生、发展过程.
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