NR2B containing NMDA receptor dependent windup of single spinal neurons
NR2B containing NMDA receptor dependent windup of single spinal neurons
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DOI：
10.1016/s0028-3908(03)00339-3
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发表时间：
2004-01-01
影响因子：
4.7
通讯作者：
Farkas, S
中科院分区：
文献类型：
--
作者：
Kovacs, G;Kocsis, P;Farkas, S
卷曲，脊髓神经元反应的频率依赖性建立，涉及伤害性通路的中枢敏化的发展。N-甲基-D-天冬氨酸（NMDA）受体已被证明参与这些过程，但在脊髓水平的各种受体亚型的作用还没有完全理解。在我们的实验中，我们比较了MK-801（一种非选择性NMDA受体拮抗剂，0.01-3 mg/kg i. v.）和CI-1041（NR 2B亚基特异性NMDA受体拮抗剂，0.3-10 mg/kg i. v.）对脊髓损伤大鼠脊髓背角神经元卷曲形成的影响。这两种类型的拮抗剂在不影响正常突触传递的剂量下显著阻断了windup。这些结果与NR 2B亚型选择性NMDA受体拮抗剂在慢性疼痛模型中充分记录的有效性一致，并首次直接证明脊髓机制参与了这种作用。(C)2003 Elsevier Ltd.保留所有权利。
Windup, the frequency dependent build-up of spinal neuronal responses, is implicated in the development of central sensitization of nociceptive pathways. N-methyl-D-aspartate (NMDA) receptors have been shown to be involved in these processes but the role of various receptor subtypes at the spinal level is not fully understood. In our experiments, we compared the inhibitory effect of MK-801 (a nonselective NMDA receptor antagonist, 0.01-3 mg/kg i.v.) and CI-1041 (an NR2B subunit specific NMDA receptor antagonist, 0.3-10 mg/kg i.v.) on the formation of dorsal horn neuronal windup in spinalized rats, in vivo. Both types of antagonist blocked windup considerably at doses not affecting the normal synaptic transmission. These results are in agreement with the well-documented effectivity of NR2B subtype selective NMDA receptor antagonists in chronic pain models and give the first direct evidence that spinal mechanisms are involved in this effect. (C) 2003 Elsevier Ltd. All rights reserved.