title: The role of spinal neurokinin-1 and glutamate receptors in hyperalgesia and allodynia induced by prostaglandin E(2) or zymosan in the rat.
abstract: Recent research has focused on prostaglandins in the central nervous system and their contribution to hyperalgesia and allodynia. This study sought to establish whether neurokinin-1 (NK-1) receptors and glutamate receptors are involved in the hyperalgesic and allodynic effects of spinally administered prostaglandin E2 (PGE2) in rats, and also to determine if the same receptors are involved the hyperalgesia induced by intraplantar administration of zymosan, an inflammatory agent which is known to evoke spinal PGE2 release. Spinal application of antagonists of the NK-1 receptor, the -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate or metabotropic glutamate receptor significantly attenuated the decrease in mechanical paw withdrawal response thresholds produced by either spinal administration of PGE2 or intraplantar administration of zymosan. The decrease in thermal paw withdrawal response latencies induced by PGE2, but not by zymosan, was significantly attenuated by spinal administration of an N-methyl--aspartate (NMDA) receptor antagonist, an AMPA/kainate receptor antagonist, or a metabotropic glutamate receptor antagonist. Allodynia induced by PGE2 was significantly alleviated by antagonists of NMDA or AMPA/kainate receptors. These results suggest that both PGE2-induced and zymosan-induced mechanical hyperalgesia are mediated in part through activation of NK-1, AMPA/kainate and metabotropic glutamate receptors. PGE2-induced, but not zymosan-induced, thermal hyperalgesia is mediated in part by activation of NMDA, AMPA/kainate and metabotropic glutamate receptors. Activation of both NMDA and AMPA/kainate receptors contribute to PGE2-induced allodynia.
authors.affiliation: Department of Psychology, University of Alabama at Birmingham, 35294, USA. mturnbach@yahoo.com
authors.forename: Meredith E
authors.initials: ME
authors.lastname: Turnbach
authors.forename: Alan
authors.initials: A
authors.lastname: Randich
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D015054:Zymosan / Q000494:pharmacology
chemical_list: D015763:2-Amino-5-phosphonovalerate; D000409:Alanine; D015232:Dinoprostone; D018691:Excitatory Amino Acid Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011810:Quinoxalines; D011812:Quinuclidines; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D018040:Receptors, Neurokinin-1; D015054:Zymosan; C000211:2-amino-3-phosphonopropionic acid; C085215:SR 140333; C056723:FG 9041