The role of non-N-methyl-D-aspartate ionotropic glutamate receptors in thespinal transmission of nociception in normal animals and animals with carrageenan inflammation

The role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate receptors in spinal nociceptive transmission in both normal animal s and animals with carrageenan inflammation was investigated using the AMPA /kainate receptor antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-di one (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-hydroisoq uinoline-3-carboxylic acid]. In normal animals, spinal administration of 10 0 mu g of LY382884 produced a significant inhibition of both the C-fibre-ev oked response and post-discharge of dorsal horn neurons, with the wind-up o f the neurons being reduced by both 50 and 100 mu g of LY382884. The spinal actions of LY382884 were enhanced following 3 h of carrageenan inflammatio n, such that doses of 20 mu g and above were able to produce significant in hibitions of the noxious-evoked response of the neurons. Spinal administrat ion of NBQX in normal animals (5-50 mu g) inhibited the C-fibre-evoked resp onse of the dorsal horn neurons, but only 50 mu g of NBQX was able to inhib it the wind-up and post-discharge of the neurons. Following 3 h of carragee nan inflammation, the ability of NBQX to inhibit the wind-up and post-disch arge of the neurons was markedly enhanced. These data suggest that both AMPA and kainate GluR5 receptors play an enhan ced role in spinal nociceptive processing following the development of peri pheral inflammation, as antagonists at both receptors are more effective ag ainst nociceptive responses, including wind-up under these inflammatory con ditions. (C) 1999 IBRO. Published by Elsevier Science Ltd.