Electrophysiological studies on the role of the NMDA receptor in nociception in the developing rat spinal cord.

The present study investigated the effects of spinally applied N-methyl-D-aspartate (NMDA) antagonists 2-amino-5-phosphonovaleric acid (AP5) and ketamine on convergent neurones in the deep dorsal horn of rats, in vivo at different postnatal ages (P) 14, 21, 28, and 56 days. AP5 inhibited the primary afferent fibre input, the C fibre, post-discharge and windup evoked responses in a dose-dependent manner at each age, and was significantly more effective in the pups than adult rats (P<0.03 at 100-microg dose). AP5 100 microg abolished windup almost completely in the pups, whilst the adults required 10-fold higher doses. In contrast there was no difference in ketamine potency between age groups. Windup in the ketamine groups was reduced in a dose-dependent manner equally across all the age groups. The differential inhibitory effects of AP5 and ketamine may be due to postnatal changes in density, localisation and receptor subunit composition, altering receptor affinity and kinetics.