Absence of prostaglandin E-2-induced hyperalgesia in NMDA receptor epsilon subunit knockout mice

1 We have previously found that intrathecal administration of prostaglandins E-2 (PGE(2)) and D-2 (PGD(2)) into conscious mice induced hyperalgesia by the hut plate test, The present study investigated the involvement of N-methyl-D-aspartate (NMDA) receptor in the prostaglandin-induced hyperalgesia by use of mice lacking NMDA receptor epsilon 1, epsilon 4, Or epsilon 1/epsilon 4 subunits, 2 PGE(2) induced hyperalgesia over a wide rang of doses from 50 pg to 500 ng kg (1)in wild-type mice, But PGE(2) 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 nan-NP IDA receptor antagonist gamma-D-glutamylaminomethyl sulphonic acid (GAMS), and the nitric oxide synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) inhibited the PGE(2)-induced hyperalgesia in wild-type mice. 4 PGD(2) induced hyperalgesia al 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 CP 96,345 blocked the PGD(2)-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 PGD(2) and PGE(2).and that both epsilon 1 and epsilon 4 subunits of the NMDA receptor are involved in the PGE(2)-induced hyperalgesia.