Effect of NMDA receptor antagonists on prostaglandin E2-induced hyperalgesia in conscious mice.
Intrathecal (i.t.) injection of prostaglandin E2 (PGE2) to conscious mice produced a hyperalgesic action over a wide range of dosages with two apparent peaks at 100 pg and 10 ng per mouse, which may be mediated through EP3 and EP2 subtypes of the PGE receptor. In the present study, the effects of NMDA receptor antagonists on hyperalgesia induced by PGE2 were evaluated by the hot plate test at 30 min after i.t. injection. Hyperalgesia induced by a higher dose of PGE2 (10 ng/mouse) was relieved by D-AP5 (a competitive antagonist), 7-Cl-KynA (a glycine site antagonist), and ketamine and MK801 (non-competitive channel blockers). Intrathecal injection of butaprost (10 ng/mouse), an EP2 agonist, induced hyperalgesia, and this hyperalgesia was blocked by D-AP5, 7-Cl-KynA, ketamine, and MK801, similar to that induced by 10 ng of PGE2. On the other hand, hyperalgesia induced by a lower dose of PGE2 (100 pg/mouse) was blocked by D-AP5 and 7-Cl-KynA, but not by ketamine and MK801. Intrathecal injection of sulprostone (100 pg/mouse), an EP1 and EP3 agonist, induced hyperalgesia, and this hyperalgesia was blocked by D-AP5 and 7-Cl-KynA, but not by ketamine and MK801, similar to that induced by 100 pg of PGE2. These results first demonstrate that the NMDA receptor is involved in the PGE2-induced hyperalgesia and suggest that the hyperalgesic action by lower and higher doses of PGE2 may be mediated through EP3 and EP2 subtypes, respectively.
Nishihara
I
I
Department of Anesthesiology, Osaka Medical College, Takatsuki, Japan.
Minami
T
T
Uda
R
R
Ito
S
S
Hyodo
M
M
Hayaishi
O
O
D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D007278:Injections, Spinal; D008297:Male; D008600:Menstruation-Inducing Agents / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D010147:Pain Measurement / Q000187:drug effects; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors
D008600:Menstruation-Inducing Agents; D011459:Prostaglandins E, Synthetic; D016194:Receptors, N-Methyl-D-Aspartate; D018078:Receptors, Prostaglandin E; C016767:sulprostone; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone