INTRATHECAL CO-ADMINISTRATION OF KAPPA OPIOID RECEPTOR AGONISTS AND NMDA RECEPTOR ANTAGONISTS INDUCES SYNERGISTIC ANALGESIA IN RATS

It is reported that intrathecal(it)injection of low dose of dynorphin(Dyn)induces no analgesia while high dose of Dyn induces analgesia and might lead to hindlimb paralysis andloss of reflex via NMDA receptor.We hypothesized that NMDA receptor antagonists may reveal kappa analgesic-potential of subliminal dose of Dyn. Twenty-four hours after intrathecal cannulation,tailflick latency was measured before and after it of drugs. Combination of Dyn A-(1-13)5 nmol orU50488H 100 nmol,a kappa receptor agonist with either DL-2-amino-5-phosphonovaleric acid(5 and10 nmol)or kynurenic acid(25 and 50 nmol)it induced synergistic analgesia,which was reversed bynor-binaltorphimine 15 nmol,a kappa receptor antagonist.It is concluded that kappa opioid receptoragonists and NMDA receptor antagonists synergistically induce analgesia via interaction with theirreceptors.