The role of non-N-methyl-D-aspartate ionotropic glutamate receptors in the spinal 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 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.
Stanfa
L C
LC
Department of Pharmacology, University College London, UK. l.stanfa@ucl.ac.uk
Dickenson
A H
AH
D000818:Animals; D002351:Carrageenan; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007278:Injections, Spinal; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009443:Neuritis / Q000139:chemically induced; D009619:Nociceptors / Q000502:physiology*; D020671:Posterior Horn Cells / Q000737:chemistry / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D002351:Carrageenan; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C400802:LY382884; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline