Involvement of peripheral NMDA and non-NMDA receptors in development of persistent firing of spinal wide-dynamic-range neurons induced by subcutaneous bee venom injection in the cat

Abstract

To study the roles of peripheral excitatory amino acids receptor subtypes N-methyl- d-aspartate (NMDA) and non-NMDA receptors in persistent nociception, extracellular single unit recording technique was used to assess the effects of a single dose NMDA and non-NMDA receptor antagonists, AP 5 (5-aminophosphonovaleric acid) and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) or DNQX (6,7-dinitroquinoxaline-2,3-dione), on s.c. bee venom-induced increase in firing of wide-dynamic-range (WDR) neurons in the spinal dorsal horn of the urethane–chloralose anesthetized cats. Subcutaneous bee venom injection into the cutaneous receptive field resulted in a single phase of increased firing of WDR neurons over the background activity for more than 1 h. Local pre-administration of AP 5 (200 μg/100 μl) or CNQX (8.3 μg/100 μl) into the bee venom injection site produced 94% (1.01±0.96 spikes/s, n=5) or 76% (2.97±0.58 spikes/s, n=4) suppression of the increased neuronal firing when compared with local saline (16.32±4.55 spikes/s, n=10) or dimethyl sulfoxide (DMSO) (12.37±6.36 spikes/s, n=4) pre-treated group, respectively. Local post-administration of the same dose of AP 5 produced a similar result to the pre-treatment group with a 67% inhibition of the mean firing rate, however, the same treatment with CNQX and even a higher dose of DNQX (100 μg/100 μl) did not produce any inhibition of the neuronal firing induced by s.c. bee venom injection (DNQX vs. DMSO: 23.91±0.25 vs. 22.14±0.04 spikes/s, P=0.0298, n=5). In the control experiments, local pre-administration of the same dose of AP 5 or CNQX into a region on the contralateral hindpaw symmetrical to the bee venom injection site produced no significant influence on the increased firing of the WDR neurons [contralateral AP 5 vs. saline: 14.17±6.27 spikes/s ( n=5) vs. 16.32±4.55 spikes/s ( n=10), P>0.05; contralateral CNQX vs. DMSO: 12.85±6.38 spikes/s ( n=4) vs. 12.37±6.36 spikes/s ( n=4), P>0.05], implicating that the suppressive action of local AP 5 or CNQX was not the result of systemic effects. The present results suggest that activation of the peripheral NMDA receptors is involved in both induction and maintenance, while activation of non-NMDA receptors is only involved in induction, but not in the maintenance of persistent firing of the dorsal horn WDR neurons induced by s.c. bee venom injection.