NR2B在神经病理性痛大鼠海马突触长时程增强易化中的作用

目的 评价含2B亚基的N-甲基-D-天冬氨酸受体(NR2B)在神经病理性痛大鼠海马突触长时程增强(LTP)易化中的作用.方法 成年雄性Wistar大鼠24只,体重180～230 g,随机分为4组(n=6):假手术组(S组),假手术+Ro25-6981组(SR组)、神经病理性痛组(NP组)和神经病理性痛+Ro25-6981组(NR组).采用结扎L4,5左侧脊神经的方法制备大鼠神经病理性痛模型.于模型制备后7、14和21 d时观察大鼠痛行为学及足部形态;于模型制备前(基础状态)、制备后7,14和21 d时测定痛阈;于最后一次痛阈测定结束后3 d记录海马CAI区兴奋性突触后电位(EPSP),以高频刺激(HFS)诱发LTP,SR组和NR组于HFS前20 min经侧脑室输注Ro25-6981(NR2B特异性阻断剂)6 μl(2.3 μg),速率1μl/min.LTP为HFS后EPSP峰值较基础值增大10%以上且维持时间≥10 min,并行LTP分级,以评价其程度.结果 与S组和SR组比较,NP组和NR组各时点痛阈降低,NP组LTP程度升高(P<0.05),NR组LTP程度差异无统计学意义(P>0.05);NR组LTP程度组低于NP组(P<0.05).结论 神经病理性痛大鼠海马突触LTP的易化可能与NR2B的激活有关.

Role of N-methyl-D-aspartate receptors containing 2B subunits in facilitation of synaptic long-term potentiation in hippocampus in rats with neuropathic pain

Objective To evaluate the role of N-methyl-D-aspartate receptors containing 2B subunits (NR2B) in the facilitation of synaptic long-term potentiation (LTP) in the hippocampus in rats with neuropathic pain. Methods Twenty-four adult male Wistar rats weighing 180-230 g were randomly divided into 4 groups (n= 6 each): sham operation group (group S), S + Ro25-6981 group (group SR), neuropathic pain group (group NP) and NP+ Ro25-6981 group (group NR). The animals were anesthetized with intraperitoneal pontobarbital 50 mg/kg. Neuropathic pain was produced by ligation of the left L4.5 spinal nerve. In group S, the left L4,5 spinal nerve were exposed but not ligated. The behaviour of the rats was evaluated. The pain threshold was measured by electric stimulation. The animals were placed in a special box with a floor made up of 18 steel bars of 0.5 cm in diameter at intervals of 1.2 cm, through which electric stimulation was induced. The intensity of electric stimulation was increased from 0.1 mA to 0.8 mA step by step until the animals screamed and lifted their hind limbs. The stimulation was repeated 6 times. The mean value was taken as pain threshold. Pain threshold was measured at 7, 14 and 21 d after surgery. The excitatory post-synaptic potential (ElXSl)) in hippocampul CA1 region was measured at 3 d after the last measurement of pain threshold. The animals were anesthetized and a hole was drilled in the skull. The recording electrodes were inserted into hippoeampal CAI region using stereotaxic technology. The changes in EPSP and input/output curve and LTP of the CA1 stralum radiatum were observed using stereutaxic technology and extracellular recordiug respectively. Results The pain threshold was significantly lower in group NP and NR, and the amplitude of LTP was significantly higher in group NP than in group S and SR (P< 0.05), but there was no significant difference in the amplitude of LTP between group NR and S and betweon group NR and SR (P > 0.05). The amplitude of LTP was significantly lower in group NR than in group NP (P < 0.05) .Conclusion The facilitation of LTP in the hippocampus in rats with neuropathic pain may be related to the activation of NR2B.