The role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (
AMPA) and
kainate receptors in spinal nociceptive transmission in both normal animals and animals with
carrageenan inflammation was investigated using the
AMPA/
kainate receptor antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (
NBQX) and the selective
GluR5 kainate receptor antagonist
LY382884 [3S,4aR,6S,8aR-6-(4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8, 8a-deca-hydroisoquinoline-3-carboxylic
acid]. In normal animals, spinal administration of 100 microg of
LY382884 produced a significant inhibition of both the C-fibre-evoked response and post-discharge of dorsal horn neurons, with the wind-up of the neurons being reduced by both 50 and 100 microg of
LY382884. The spinal actions of
LY382884 were enhanced following 3 h of
carrageenan inflammation, such that doses of 20 microg and above were able to produce significant inhibitions of the noxious-evoked response of the neurons. Spinal administration of
NBQX in normal animals (5-50 microg) inhibited the C-fibre-evoked response of the dorsal horn neurons, but only 50 microg of
NBQX was able to inhibit the wind-up and post-discharge of the neurons. Following 3 h of
carrageenan inflammation, the ability of
NBQX to inhibit the wind-up and post-discharge of the neurons was markedly enhanced. These data suggest that both
AMPA and
kainate GluR5 receptors play an enhanced role in spinal nociceptive processing following the development of peripheral
inflammation, as antagonists at both receptors are more effective against nociceptive responses, including wind-up under these inflammatory conditions.