Nishihara I, Minami T, Uda R, Ito S, Hyodo M, Hayaishi O
Department of Anesthesiology, Osaka Medical College, Takatsuki, Japan.
Brain Res. 1995 Apr 17;677(1):138-44. doi: 10.1016/0006-8993(95)00133-b.
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.
向清醒小鼠鞘内注射前列腺素E2（PGE2），在很宽的剂量范围内都会产生痛觉过敏作用，每只小鼠注射100 pg和10 ng时出现两个明显的峰值，这可能是通过PGE受体的EP3和EP2亚型介导的。在本研究中，通过热板试验在鞘内注射30分钟后评估NMDA受体拮抗剂对PGE2诱导的痛觉过敏的影响。较高剂量的PGE2（10 ng/小鼠）诱导的痛觉过敏可被D-AP5（一种竞争性拮抗剂）、7-Cl-KynA（一种甘氨酸位点拮抗剂）、氯胺酮和MK801（非竞争性通道阻滞剂）缓解。鞘内注射EP2激动剂布他前列素（10 ng/小鼠）可诱导痛觉过敏，这种痛觉过敏被D-AP5、7-Cl-KynA、氯胺酮和MK801阻断，类似于10 ng PGE2诱导的痛觉过敏。另一方面，较低剂量的PGE2（100 pg/小鼠）诱导的痛觉过敏被D-AP5和7-Cl-KynA阻断，但未被氯胺酮和MK801阻断。鞘内注射EP1和EP3激动剂舒前列素（100 pg/小鼠）可诱导痛觉过敏，这种痛觉过敏被D-AP5和7-Cl-KynA阻断，但未被氯胺酮和MK801阻断，类似于100 pg PGE2诱导的痛觉过敏。这些结果首次证明NMDA受体参与PGE2诱导的痛觉过敏，并表明较低和较高剂量PGE2的痛觉过敏作用可能分别通过EP3和EP2亚型介导。
