神经病理性疼痛老年大鼠海马突触长时程抑制的变化
Changes in Hippocampus Synapses Caused by Long-term Depression in Old Rats with Neuropathic Pain
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摘要: 目的 探讨神经病理性疼痛老年大鼠海马CA1区突触长时程抑制 (LTD) 的变化.方法 老年雄性Wistar大鼠15只, 随机均分为3组 (n=5) :假手术组 (S组) 、神经病理性疼痛模型组 (NP组) 、NP+AP5组 (NA组) .采用结扎L4, L5右侧脊神经的方法制备神经病理性疼痛模型.于模型制备后7 d、14 d和21 d观察大鼠痛行为学及足部形态, 于模型制备前 (基础值) 、制备后7 d、14 d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CA1区兴奋性突触后膜电位 (EPSP) , 以低频刺激 (LFS) 诱发LTD.NA组LFS前20 min经侧脑室给予输注AP5 (NMDA特异性拮抗剂) 6μL (11.8μg) .结果 与S组比较, NP组和NA组各时点痛阈降低, NP组各时段LTD减小 (P<0.05) ;S组与NA组相比LTD差异无统计学意义 (P>0.05) .结论 结扎L4, L5右侧脊神经所致的神经病理性疼痛可易化老年大鼠海马CA1区突触LTD;机制可能与NMDA受体活化相关.Abstract: Objective To investigate the changes in Hippocampus synapses caused by long-term depression (LTD) in old rats with neuropathic pain. Method Fifteen old male Wistar rats were randomly divided into 3 groups (n = 5 each) : sham operating group (group S) , neuropathic pain group (group NP) , and NP + AP5 group (group NA) . Neuropathic pain was produced by ligation of the right L4, L5 spinal nerve. The behaviour of the rats was evaluated. The pain threshold was measured by electric stimulation at 7, 14 and 21 d after surgery. The excitatory post-synaptic potential (EPSP) in hippocampal CA1 region was recorded at 3 d after the last measurement of pain threshold. The changes in EPSP and input/output curve and LTD induced by low frequency stimulation (LFS) of the CA1 stratum radiatum of the rat hippocampus were observed using stereotaxic technology and extracellular recording respectively. Group NA received infusion of AP5 (NMDA receptor antagonist) 6 μl by i.c.v 20 min before LFS. Results The pain threshold was significantly lower in group NP and NA than in group S.The amplitude of LTD was significantly lower in group NP than in group S and NA (P<0.05) , but there was no significant difference in the amplitude of LTD between group S and NA (P>0.05) . Conclusion The results suggest that the neuropathic pain by ligation of the right L4, L5 spinal nerve might facilitate LTD induction in the CA1 area of the hippocampus of old rats; mechanism might be related to the activation of NMDA receptors.
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Key words:
- Neuralgia /
- Long-term depression /
- Hippocampus /
- Rat /
- Aged
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[1] [1]DURIC V, MCCARSON K E.Persistent pain produces stress-like alterations in hippocampal neurogenesis and gene expression[J].J Pain, 2006, 7 (8) :544-555. [2]魏辉明, 麻伟青, 李治贵, 等.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[J].中华麻醉学杂志, 2009, 29 (9) :789-792. [3] 魏辉明, 麻伟青, 王慧明, 等.神经病理性痛大鼠海马突触长时程增强的变化[J].中华麻醉学杂志, 2008, 28 (10) :895-897. [4]麻伟青, 魏辉明, 董发团, 等.腰4/5脊神经结扎大鼠慢性神经病性痛模型的建立[J].昆明医学院学报, 2010, 31 (6) :57-60. [5] [5]RODGERS R J.Effects of nicotine, mecamylamine, and hexamethonium on shock induced fighting, pain reactivity, and locomotor behaviour in rats[J].Psychopharmacology, 1979, 66 (1) :93-98. [6] [6]WANG M, YANG Y, DONG Z, et al.NR2B-containing N-methyl-D-aspartate subtype glutamate receptors regulate the acute stress effect on hippocampal long-term potentiation/long-term depression in vivo[J].Neuroreport, 2006, 17 (12) :1343-1346. [7] [7]SOUZA A, DUSSAN-SARRIA J A, MEDEIROS L F, et al.Neonatal hypoxic-ischemic encephalopathy reduces c-Fos activation in the rat hippocampus:Evidence of a long-lasting effect[J].Int J Dev Neurosci, 2014, 38 (9) :213-222. [8] [8]PERCIE DU SERT N, RICE AS.Improving the translation of analgesic drugs to the clinic:Animal models of neuropathic pain[J].Br J Pharmacol, 2014, 171 (12) :2951-2963. [9] [9]JEAN-MARC G, MICHAEL B, ZHANG M, et al.Neuronal changes induced by Varicella Zoster Virus in a rat model of postherpetic neuralgia[J].Virology, 2015, 482 (3) :167-180. [10] [10]SANDKUHLER J.Learning and memory in pain pathways[J].Pain, 2000, 88 (2) :113-118. [11] [11]DONG Z, ZHONG W, TIAN M, et al.Stress evoked by opiate withdrawal facilitates hippocampal LTP in vivo[J].Hippocampus, 2006, 16 (12) :1017-1025. [12] [12]GILBERT M E, MACK C M.Field potential recordings in dentate gyrus of anesthetized rats:stability of baseline[J].Hippocampus, 1999, 9 (3) :277-287. [13] [13]ZHUO M.A synaptic model for pain:long-term potentiation in the anterior cingulate cortex[J].Mol Cells, 2007, 23 (3) :259-271. [14] [14]KERVERN M, SILVESTRE DE FERRON B, ALAUXCANTIN S, et al.Aberrant NMDA-dependent LTD after perinatal ethanol exposure in young adult rat hippocampus[J].Hippocampus, 2015, 25 (8) :912-923. [15] [15]BHOURI M, FARROW P A, MOTEE A, et al.m Glu1 Receptor-induced LTD of NMDA receptor transmission selectively at schaffer collateral-CA1 synapses mediates metaplasticity[J].J Neurosci, 2014, 34 (36) :12223-12229. 期刊类型引用(10)
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