Advokat C, Rutherford D
Department of Psychology, Louisiana State University, Baton Rouge 70803, USA.
Pharmacol Biochem Behav. 1995 Aug;51(4):855-60. doi: 10.1016/0091-3057(95)00058-5.
Results of neurophysiologic and behavioral studies suggest that excitatory amino acid (EAA) antagonists may provide a new class of analgesic agents, which might be selective for neuropathic pain states that are resistant to opiate treatment. Most of these paradigms involve animal models of peripheral injury. The present study evaluated the antinociceptive effect of spinally [intrathecally (IT)] administered EAA antagonists after central injury, produced by spinal transection. Intrathecal injection of the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione produced dose-dependent antinociception on the thermal tail withdrawal [tail-flick (TF)] reflex test in Intact rats, which was significantly potentiated after spinal transection. In contrast, IT injection of the NMDA antagonist, 2-amino-5-phosphonopentanoic acid (AP5) did not affect the TF in intact rats, but significantly blocked this response in spinal rats. However, some of the spinal rats did not recover the reflex, suggesting a possible toxic action of AP5.
神经生理学和行为学研究结果表明，兴奋性氨基酸（EAA）拮抗剂可能会提供一类新的镇痛药，这类药物可能对阿片类药物治疗无效的神经性疼痛状态具有选择性。这些研究范式大多涉及外周损伤的动物模型。本研究评估了脊髓横断造成中枢损伤后，鞘内注射EAA拮抗剂的抗伤害感受作用。鞘内注射AMPA/海人藻酸受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮对完整大鼠的热尾撤离[甩尾（TF）]反射试验产生剂量依赖性抗伤害感受作用，脊髓横断后该作用显著增强。相比之下，鞘内注射NMDA拮抗剂2-氨基-5-磷酸戊酸（AP5）对完整大鼠的TF无影响，但能显著阻断脊髓大鼠的这一反应。然而，一些脊髓大鼠并未恢复该反射，提示AP5可能具有毒性作用。
