PREEMPTIVE INTRATHECAL MK-801, A NONCOMPETITIVE N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST, INHIBITS THE UP-REGULATION OF SPINAL DYNORPHIN MESSENGER-RNA AND HYPERALGESIA IN A RAT MODEL OF CHRONIC INFLAMMATION

The effects of N-methyl-D-aspartate(NMDA) receptor antagonist, Mk-801, on the expression of spinal dynorphin (DYN) mRNA and the hyperalgesia induced by peripheral inflammation were studied by Northern analysis and behavioral test. Following an unilateral injection of complete Fre und's adjuvant (CFA) into the rat hindpaw, there appeared a significan t hyperalgesia of inflamed hindpaw and up-regulation of ipsilateral sp inal DYN mRNA; while the pre-emptive and continuous intrathecal admini stration of Mk-801 (10 mu g/mu l per h) could significantly suppress b oth the hyperalgesia and the up-regulation of spinal DYN mRNA induced by peripheral inflammation. The results suggest that NMDA receptor act ivation may contribute to the development and maintenance of the therm al hyperalgesia that is associated with the up-regulation of DYN expre ssion in spinal dorsal horn. (C) 1998 Elsevier Science Ireland Ltd.