title: Involvement of glutamate receptors in allodynia induced by prostaglandins E2 and F2 alpha injected into conscious mice.
abstract: In order to investigate the involvement of glutamate receptor systems in allodynia induced by prostaglandin (PG) E2 or F2 alpha, we co-administered antagonists for N-methyl-D-aspartate (NMDA), non-NMDA, or metabotropic glutamate receptors intrathecally with PGE2 or PGF2 alpha and examined their effects on the allodynia evoked in conscious mice by non-noxious brushing of the flanks. MK-801, a non-competitive NMDA receptor channel blocker, and D-AP-5, a selective NMDA receptor antagonist, dose-dependently blocked PGE2-induced allodynia with an IC50 of 1.60 and 0.52 microgram/mouse, respectively. A glycine binding-site antagonist for the NMDA receptor, 7-Cl-KYNA, did not influence it. None of these NMDA receptor antagonists inhibited PGF2 alpha-evoked allodynia. Non-NMDA receptor antagonists GAMS and CNQX inhibited both PGE2- and PGF2 alpha-induced allodynia. On the other hand, L-AP-3 and L-AP-4, putative metabotropic glutamate receptor antagonists, dose-dependently antagonized the allodynia induced by PGF2 alpha with an IC50 of 0.92 and 3.26 ng/mouse, respectively, but not that induced by PGE2. Intrathecal administration of L-glutamate produced allodynia over a wide range of low doses from 0.1 pg to 0.1 microgram/mouse, and the maximal effect was observed at 1 ng. Similar to allodynia induced by prostaglandins, the response lasted over a 50-min experimental period. These results demonstrate that both PGE2- and PGF2 alpha-evoked allodynia are mediated through a pathway that includes the glutamate receptor system but that subtypes of glutamate receptors involved and sites of action in the spinal cord may be different between them.
authors.affiliation: Department of Anesthesiology, Osaka Medical College, TakatsukiJapan Department of Cell Biology, Osaka Bioscience Institute, SuitaJapan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Minami
authors.forename: Isao
authors.initials: I
authors.lastname: Nishihara
authors.forename: Rumiko
authors.initials: R
authors.lastname: Uda
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Hyodo
authors.forename: Osamu
authors.initials: O
authors.lastname: Hayaishi
mesh_terms: D000818:Animals; D015237:Dinoprost / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007278:Injections, Spinal; D051379:Mice; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D005971:Glutamates; D018377:Neurotransmitter Agents; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D015237:Dinoprost; D015232:Dinoprostone