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-a spartate (NMDA) antagonists 2-amino-5-phosphonovaleric acid (AP5) and ketam ine on convergent neurones in the Jeep dorsal horn of rats, in vivo at diff erent postnatal ages (P) 14, 21, 28, and 56 days. AP5 inhibited the primary afferent fibre input, the C fibre, post-discharge and windup evoked respon ses in a done-dependent manner at each age, and was significantly more effe ctive in the pups than adult rats (P<0.03 at 100-<mu>g dose). AP5 100 mug a bolished windup almost completely in the pups, whilst the adults required 1 0-fold higher doses. In contrast there was no difference in ketamine potenc y between age groups. Windup in the ketamine groups was reduced in a dose-d ependent manner equally across all the age groups. The differential inhibit ory effects of AP5 and ketamine may be due to postnatal changes in density, localisation and receptor subunit composition, altering receptor affinity and kinetics. (C) 2001 Elsevier Science B.V. All rights reserved.