Spinal cord long-term potentiation is attenuated by the NMDA-2B receptor antagonist Ro 25-6981

The NR2B-containing N-methyl-d-aspartate (NMDA) receptors may be involved in a variety of phenomena including synaptic plasticity, memory formation and pain perception. Here we used the NMDA-2B receptor antagonist Ro 25-6981 to investigate the role of the NR2B-containing NMDA receptors in spinal nociception.

Extracellular single unit recordings were performed from dorsal horn wide dynamic range (WDR) neurones in intact urethane-anaesthetized Sprague-Dawley rats. The responses of the WDR neurones evoked by C-fibre activation after sciatic nerve stimulation were defined according to latencies. To block the dorsal horn NMDA-2B receptors, the antagonist Ro 25-6981 was applied topically onto the spinal cord. High-frequency stimulation (HFS) of the sciatic nerve was used to induce spinal long-term potentiation (LTP).

Spinal administration of the NMDA-2B receptor antagonist Ro 25-6981 had a clear antinociceptive effect at the spinal level (P < 0.05, C-fibre evoked responses after 4 mm Ro 25-6981 vs. C-fibre evoked responses in baseline). Moreover, spinal administration of this antagonist clearly attenuated the magnitude of spinal cord LTP after HFS conditioning (P < 0.05, C-fibre evoked responses after HFS vs. C-fibre evoked responses after 8 mm Ro 25-6981 + HFS).

The present study indicates that expression of full LTP in dorsal horn neurones obtained by HFS conditioning may be dependent on the NMDA receptors containing the NR2B subunit. This suggests that activation of dorsal horn NR2B-containing NMDA receptors may be involved in use-dependent sensitization at the spinal level.