Peripheral administration of NMDA, AMPA or KA results in pain behaviors in rats.
The present study investigated the role of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor subtypes in peripheral pain transmission. Activation of NMDA, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate acid (KA) receptors in glabrous skin of the rat hindpaw resulted in mechanical allodynia and mechanical hyperalgesia. These agonist-induced pain behaviors were attenuated following peripheral injection of appropriate antagonists (MK-801 and CNQX). Thus, activation of NMDA, AMPA or KA receptors at the level of the peripheral nerve terminal can produce nociceptive behavior. These data suggest that topical application of glutamate receptor antagonists may be useful in treating pain disorders. Since all three receptor subtypes are involved in peripheral pain transmission, however, it will be necessary to antagonize multiple glutamate receptor subtypes to achieve effective pain relief.
Zhou
S
S
Department of Anatomy and Neuroscience, University of Texas Medical Branch, Galveston 77555-1069, USA.
Bonasera
L
L
Carlton
S M
SM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006614:Hindlimb; D007608:Kainic Acid / Q000633:toxicity*; D016015:Logistic Models; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity*
D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D016202:N-Methylaspartate; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid