Differential effect of peripheral glutamate (NMDA, non-NMDA) receptor antagonists on bee venom-induced spontaneous nociception and sensitization

Abstract

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 (0.2 mg/50 μl) 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 (10 mM, 50 μl) and both pre-treatment and post-treatment with MK-801 (2 mM, 50 μl) 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 (5 mM, 50 μl) 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.