Kovács Gyula, Kocsis Pál, Tarnawa István, Horváth Csilla, Szombathelyi Zsolt, Farkas Sándor
Pharmacological and Drug Safety Research, Gedeon Richter Ltd., P.O. Box 27, H-1475, Budapest 10, Hungary.
Neuropharmacology. 2004 Jan;46(1):23-30. doi: 10.1016/s0028-3908(03)00339-3.
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.
windup现象，即脊髓神经元反应的频率依赖性增强，与伤害性感受通路中枢敏化的发展有关。N-甲基-D-天冬氨酸（NMDA）受体已被证明参与这些过程，但各种受体亚型在脊髓水平的作用尚未完全了解。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，静脉注射剂量为0.01-3mg/kg）和CI-1041（一种NR2B亚基特异性NMDA受体拮抗剂，静脉注射剂量为0.3-10mg/kg）对脊髓损伤大鼠背角神经元windup形成的抑制作用。两种拮抗剂在不影响正常突触传递的剂量下都能显著阻断windup现象。这些结果与NR2B亚型选择性NMDA受体拮抗剂在慢性疼痛模型中的有效性一致，并首次直接证明脊髓机制参与了这一效应。
