EFFECTS OF INTRATHECAL MU-AGONIST, DELTA-AGONIST AND KAPPA-AGONIST ONTHERMALLY EVOKED CARDIOVASCULAR AND NOCICEPTIVE REFLEXES IN HALOTHANE-ANESTHETIZED RATS

Despite significant opioid binding in the intermediolateral cell colum n, the effects of intrathecal injections of mu, delta and kappa opioid agonists on the cardiovascular response to noxious stimulation have n ot been examined systematically. The pharmacology of intrathecally adm inistered opioid agonists {mu, morphine, [D-Ala(2),N-MePhe(4),Gly(5)-o l]enkephalin (DAGO); delta, metkephamid, [D-Ala(2)-D-Leu(5)]enkephaiin (DADL), [D-Pen(2),D-Pen(5)]enkephalin (DPDPE); kappa, U50488H and PD1 17,302} or agonist-antagonist (nalbuphine) on somatomotor (tail-flick) and cardiovascular changes (blood pressure and heart rate) evoked by immersing the tail in 53 degrees C water were examined in rats anesthe tized with halothane (0.75%) and in which intrathecal catheters had be en chronically implanted. Intrathecal administration of mu and delta, but not kappa agonists or agonist-antagonist produced a dose-dependent block of tail-flick and evoked cardiovascular responses with the orde r of activity being as follows: DAGO > metkephamid DADL > morphine > D PDPE much greater than nalbuphine = PD117,302 = U50488H = O. These eff ects were reversed readily by the opioid antagonist naloxone. In addit ion, intrathecal administration of mu and delta but not kappa or agoni st-antagonist had Little effect on resting heart rate and blood pressu re. These data indicate that the agonist occupancy of spinal mu and de lta, but not kappa agonists can profoundly modulate the autonomic and somatomotor response evoked by high threshold thermal stimuli.