氯胺酮对神经病理性痛大鼠海马长时程增强维持的影响

摘要

目的 探讨氯胺酮对神经病理性痛大鼠海马CA1区突触长时程增强(LTP)维持的影响.方法 成年雄性Wistar大鼠15只,随机均分为三组:神经病理性痛模型组(NP组)、氯胺酮1组(K1组)、氯胺酮2组(K2组).采用结扎L4.5左侧脊神经的方法制备大鼠模型,于术前、术后1、2和3周观察大鼠痛行为学及足部形态；于术前、术后1、2和3周测定痛阈；于最后一次痛阈测定结束后3d记录海马CA1区兴奋性突触后电位(EPSP),以高频刺激(HFS)诱发LTP.K1组于HFS前20 min经腹腔注射氯胺酮25 mg/kg,K2组HFS后60 min腹腔注射氯胺酮25 mg/kg.结果 与术前比较,术后三组各时点痛阈降低(P＜0.05)；与基础值比较,NP组与K2组HFS后各时段EPSP幅值升高(P＜0.05),与NP组和K2组比较,K1组HFS后各时段降低(P＜0.05).结论 氯胺酮可阻滞神经病理性痛大鼠海马CA1区突触LTP的诱导,但不干扰维持.%Objective To investigate the effect of ketamine on maintenance of synaptic long-term potentiation (LTP) in hippocampus in rats with neuropathic pain. Methods Fifteen adult male Wistar rats were randomly divided into 3 groups (n = 5 each): group neuropathic pain (group NP), group ketamine 1 (group Kl) and group ketamine 2 (group K2). Neuropathic pain was produced by ligation of the left L4.5 spinal nerve. The behaviour of the rats was evaluated. Pain threshold was measured at 1, 2 and 3 week after surgery. The excitatory post-synaptic potential (EPSP) in hippocampal Cal region was measured at 3 d after the last measurement of pain threshold. The changes in EPSP and LTP induced by high frequency stimulation( HFS) of the Cal stratum radiatum of the rat hippocampus were observed using stereotaxic technology and extracellular recording respectively. Group Kl received ketamine (25 mg/kg I. P) 20 min before HFS. Group K2 received the same dose 60 min after HFS. Results The pain threshold was significantly lower in 3 groups after surgery. The amplitudes of EPSP were significantly higher in group NP and K2 after HFS compared to baseline (P<0. 05), and that in group Kl was lower than those in group NP and K2 (P<0. 05). Conclusion The results suggest that Ketamine might inhibit the induction of synaptic LTP by neuropathic pain in the Cal area of the hippocampus, but not affect the maintenance.