NMDA receptor involvement in spinal inhibitory controls of nociception in the rat.

Low frequency electrical stimulation of high threshold sensory afferents elicits a prolonged inhibition of nociceptive mechanisms in the lightly anaesthetized rat. The present study was to determine the role of NMDA receptor activation in mediation of this inhibition. The latency of the tail withdrawal from a noxious thermal test stimulus to the tip of the tail was taken as an indication of the excitability of nociceptive pathways. Conditioning electrical stimulation at 20 times threshold for muscle twitch with 2 ms pulses at 4 Hz for 20 min applied to previously defined meridian points in the hindlimb evoked a 70% inhibition of the tail withdrawal reflex in rats which received an intrathecal injection of CSF (n = 11) compared with unstimulated controls (n = 10). This inhibition lasted > 1 h after the end of the conditioning stimulus. The competitive NMDA receptor antagonist 5-amino-2-phosphonovaleric acid (APV) blocked the inhibition during the stimulus and during the post-stimulation period. It is concluded that activation of NMDA receptors is critical for the expression of the long-term plastic changes in the central nervous system which result in the persistent inhibition of the nociceptive tail withdrawal reflex.