Effects of excitatory amino acid receptor antagonists on a capsaicin-evoked nociceptive reflex: a comparison with morphine, clonidine and baclofen.

The rat isolated spinal cord-tail preparation has been employed to examine the effects of several antinociceptive drugs and excitatory amino acid (EAA) receptor antagonists on nociceptive reflexes (recorded in ventral roots) stimulated by peripheral application of capsaicin (CAP). Non-nociceptive monosynaptic and polysynaptic dorsal root-evoked ventral root potentials (DR-VRPs) were also examined. Morphine (0.01-3 microM) and clonidine (0.03-1 microM) inhibited CAP-stimulated activity, but not the non-nociceptive dorsal root-evoked monosynaptic reflex (MSR) or polysynaptic (PSR) activity. These effects were antagonized by naloxone and efaroxan, respectively. The AMPA/KA receptor antagonists CNQX (0.1-100 microM) and DNQX (0.1-30 microM) blocked nociceptive activity and were 4-fold selective for CAP-evoked potentials compared to the monosynaptic reflex. Kynurenate (1-300 microM), DL-AP-4 (3-300 microM), L-AP-4 (3-300 microM), and the GABAB receptor agonist baclofen (0.1-10 microM), inhibited all evoked potentials with relatively little selectivity between nociceptive and non-nociceptive responses. NMDA receptor antagonism by AP-5 (100 microM) reduced nociceptive and non-nociceptive potentials by a maximum of 30-33%. These data indicate that AMPA/KA receptor-mediated synapses are involved in acute spinal nociceptive transmission and suggest that AMPA/KA receptor subtypes could provide novel analgesic targets.