Absence of prostaglandin E2-induced hyperalgesia in NMDA receptor epsilon subunit knockout mice.
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.
Minami
T
T
Department of Anesthesiology, Osaka Medical College, Takatsuki, Japan.
Sugatani
J
J
Sakimura
K
K
Abe
M
M
Mishina
M
M
Ito
S
S
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*
D016194:Receptors, N-Methyl-D-Aspartate; D015232:Dinoprostone; D015230:Prostaglandin D2