Dorsal horn NMDA receptor function is changed after peripheral inflammation.

The N-methyl-D-aspartic acid (NMDA) receptor antagonist D, L-2-amino-5-phosphonopentanoic acid (AP5) caused a stronger inhibition of wind-up in single wide dynamic range (WDR) neurons after carrageenan inflammation compared with control neurons without inflammation in the receptive field. This indicates that even a short period (2.5 h) of inflammation induces changes in the function of NMDA receptors. The drug effect was also studied in separate control experiments with few wind-up inducing stimulus trains and little nociceptive input prior to baseline recordings. In these control experiments all evoked responses were reduced by the drug, but the wind-up was significantly increased. A wind-up increase after NMDA receptor antagonism has been reported in two previous studies. Thus, other mechanisms than NMDA receptor stimulation may be more important for the wind-up in not sensitized dorsal horn neurons. As for long-term potentiation, it seems that NMDA receptor antagonists have an increased effect after sensitization. Thus, sensitized and not sensitized dorsal horn neurons may respond differently to an NMDA receptor active drug. In rats nerve stimulation and halothane anaesthesia induced larger evoked responses to afferent stimulation than cutaneous stimulation and urethane anaesthesia, the AP5 effect was however similar.