title: Absence of prostaglandin E2-induced hyperalgesia in NMDA receptor epsilon subunit knockout mice.
abstract: 1. We have previously found that intrathecal administration of prostaglandins E2 (PGE2) and D2 (PGD2) into conscious mice induced hyperalgesia by the hot plate test. The present study investigated the involvement of N-methyl-D-aspartate (NMDA) receptor in the prostaglandin-induced hyperalgesia by use of mice tacking NMDA receptor epsilon 1, epsilon 4, or epsilon 1/epsilon 4 subunits. 2. PGE2 induced hyperalgesia over a wide range of doses from 50 pg to 500 ng kg-1 in wild-type mice. But PGE2 could not induce hyperalgesia in epsilon 1, epsilon 4, or epsilon 1/epsilon 4 subunit knockout mice. 3. The NMDA receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid (D-AP5), the non-NMDA receptor antagonist 7-D-glutamylaminomethyl sulphonic acid (GAMS), and the nitric oxide synthase inhibitor N epsilon-nitro-L-arginine methyl ester (L-NAME) inhibited the PGE2-induced hyperalgesia in wild-type mice. 4. PGD2 induced hyperalgesia at doses of 25 ng to 250 ng kg-1 in both wild-type and epsilon 1/epsilon 4 subunit knockout mice. The substance P receptor antagonist OP 96.345 blocked the PGD2-induced hyperalgesia in wild-type and epsilon 1/epsilon 4 subunit knockout mice. 5. These results demonstrate that the pathways leading to hyperalgesia are different between PGD2 and PGE2, and that both epsilon 1 and epsilon 4 subunits of the NMDA receptor are involved in the PGE2-induced hyperalgesia.
authors.affiliation: Department of Anesthesiology, Osaka Medical College, Takatsuki, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Minami
authors.forename: J
authors.initials: J
authors.lastname: Sugatani
authors.forename: K
authors.initials: K
authors.lastname: Sakimura
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Mishina
authors.forename: S
authors.initials: S
authors.lastname: Ito
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D015232:Dinoprostone; D015230:Prostaglandin D2