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

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 effe cts of a single dose NMDA and non-NMDA receptor antagonists, AP(5) (5-amino phosphonovaleric acid) and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) or D NQX (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 injectio n into the cutaneous receptive field resulted in a single phase of increase d firing of WDR neurons over the background activity for more than 1 h. Loc al pre-administration of AP, (200 mu g/100 mu l) or CNQX (8.3 mu g/100 mu l ) 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 n euronal 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-tre ated group, respectively. Local post-administration of the same dose of AP( 5) produced a similar result to the pre-treatment group with a 67% inhibiti on of the mean firing rate, however, the same treatment with CNQX and even a higher dose of DNQX (100 mu g/100 mu l) 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 contro l experiments, local pre-administration of the same dose of AP, or CNQX int o a region on the contralateral hindpaw symmetrical to the bee venom inject ion site produced no significant influence on the increased firing of the W DR 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. DMS O: 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 activa tion of the peripheral NMDA receptors is involved in both induction and mai ntenance, while activation of non-NMDA receptors is only involved in induct ion, but not in the maintenance of persistent firing of the dorsal horn WDR neurons induced by s.c. bee venom injection. (C) 1999 Published by Elsevie r Science B.V. All rights reserved.