Blocking NMDA receptors in the hippocampal dentate gyrus with AP5 producesanalgesia in the formalin pain test

The hippocampus is an integral component of the "limbic" system and, as suc h, may contribute to the negative affect and avoidance motivation experienc ed during pain. A substantial body of evidence indicates that the hippocamp us processes pain-related information, that some hippocampal neurons respon d exclusively to painful stimulation, and that long-term anatomical changes occur in dentate gyrus neurons, following noxious physical stimulation. NM DA receptor antagonist drugs administered to the hippocampus interfere with long-term potentiation, learning, and memory; these same drugs, when appli ed to the spinal cord, prevent the long-term neurophysiological changes cau sed by noxious physical stimulation. This experiment tested whether blockin g NMDA receptors in the hippocampal formation reduces nociceptive behaviors in an animal model of persistent human pain. The competitive NMDA receptor antagonist AP5 was injected into the dentate gyrus of alert, unrestrained rats either 5 min before or 15 min following the administration of a subcut aneous injection of formalin irritant. Pain behaviors in both acute and ton ic phases of the formalin test were significantly reduced by AP5 treatments . These results support the hypothesis that the hippocampal formation is in volved in pain-related neural processing and that NMDA receptor-sensitive m echanisms in the hippocampus are involved in pain perception and/or the exp ression of pain-related behaviors. (C) 2001 Academic Press.