You Hao-Jun, Chen Jun, Morch Carsten Dahl, Arendt-Nielsen Lars
Center for Sensory-Motor Interaction (SMI), Laboratory for Experimental Pain Research, Aalborg University, Aalborg, Denmark.
Brain Res Bull. 2002 Sep 30;58(6):561-7. doi: 10.1016/s0361-9230(02)00806-7.
This study aimed to investigate the role of peripheral N-methyl-d-aspartate (NMDA) and non-NMDA receptor on (1). spontaneous nociception and (2). on sensitization induced by subcutaneous (s.c.) injection of bee venom (0.2mg/50 micro l) in rats. Peripheral s.c. administration of the competitive NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (AP5), the non-competitive NMDA receptor channel blocker MK-801, and the competitive non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were performed before (pre-treatment) and after (post-treatment) bee venom-induced inflammation. Pre-treatment with AP5 (10mM, 50 micro l) and both pre-treatment and post-treatment with MK-801 (2mM, 50 micro l) into the same area of the bee venom injection site markedly reduced the bee venom-increased spontaneous responses of wide-dynamic range (WDR) neuron of the spinal cord. Post-treatment with the same dose of AP5 as well as pre-treatment and post-treatment with CNQX (5mM, 50 micro l) did not produce any inhibitory effects. Additionally, the role of peripheral NMDA and non-NMDA receptors on bee venom-induced mechanical allodynia and hyperalgesia were investigated and assessed by the paw withdrawal reflex to the innocuous and noxious mechanical stimulation. Peripheral administration of AP5, but not CNQX, reduced mechanical allodynia and hyperalgesia. The data suggest that the peripheral NMDA receptor, but not non-NMDA receptor, plays a pivotal role in the bee venom-induced persistent nociception and hyperexcitability.
本研究旨在探讨外周N-甲基-D-天冬氨酸（NMDA）和非NMDA受体在以下两方面的作用：（1）自发痛觉；（2）皮下注射蜂毒（0.2mg/50微升）诱导大鼠产生敏化作用。在蜂毒诱导炎症之前（预处理）和之后（后处理），对大鼠外周皮下给予竞争性NMDA受体拮抗剂DL-2-氨基-5-磷酸戊酸（AP5）、非竞争性NMDA受体通道阻滞剂MK-801以及竞争性非NMDA受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）。向蜂毒注射部位的同一区域预处理AP5（10mM，50微升）以及预处理和后处理MK-801（2mM，50微升），可显著降低蜂毒诱导的脊髓广动力范围（WDR）神经元自发反应增强。用相同剂量的AP5进行后处理以及用CNQX（5mM，50微升）进行预处理和后处理均未产生任何抑制作用。此外，通过对无害和有害机械刺激的爪退缩反射，研究并评估外周NMDA和非NMDA受体对蜂毒诱导的机械性异常性疼痛和痛觉过敏的作用。外周给予AP5而非CNQX可减轻机械性异常性疼痛和痛觉过敏。数据表明，外周NMDA受体而非非NMDA受体在蜂毒诱导的持续性伤害感受和兴奋性过高中起关键作用。
