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.