Selective antinociceptive effect of excitatory amino acid antagonists in intact and acute spinal rats

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.