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.
摘要
我们之前发现，向清醒小鼠鞘内注射前列腺素E2（PGE2）和前列腺素D2（PGD2）可通过热板试验诱导痛觉过敏。本研究利用敲除N-甲基-D-天冬氨酸（NMDA）受体ε1、ε4或ε1/ε4亚基的小鼠，探究了NMDA受体在前列腺素诱导的痛觉过敏中的作用。2. 在野生型小鼠中，PGE2在50 pg至500 ng kg-1的广泛剂量范围内均可诱导痛觉过敏。但PGE2在ε1、ε4或ε1/ε4亚基敲除小鼠中不能诱导痛觉过敏。3. NMDA受体拮抗剂D-(-)-2-氨基-5-磷酸戊酸（D-AP5）、非NMDA受体拮抗剂7-D-谷氨酰胺甲基磺酸（GAMS）以及一氧化氮合酶抑制剂Nε-硝基-L-精氨酸甲酯（L-NAME）均可抑制野生型小鼠中PGE2诱导的痛觉过敏。4. 在野生型和ε1/ε4亚基敲除小鼠中，PGD2在25 ng至250 ng kg-1的剂量下均可诱导痛觉过敏。P物质受体拮抗剂OP 96.345可阻断野生型和ε1/ε4亚基敲除小鼠中PGD2诱导的痛觉过敏。5. 这些结果表明，PGD2和PGE2导致痛觉过敏的途径不同，且NMDA受体的ε1和ε4亚基均参与了PGE2诱导的痛觉过敏。
