EFFECTS OF INTRATHECAL MU-AGONIST, DELTA-AGONIST AND KAPPA-AGONIST ONTHERMALLY EVOKED CARDIOVASCULAR AND NOCICEPTIVE REFLEXES IN HALOTHANE-ANESTHETIZED RATS
H. Nagasaka et Tl. Yaksh, EFFECTS OF INTRATHECAL MU-AGONIST, DELTA-AGONIST AND KAPPA-AGONIST ONTHERMALLY EVOKED CARDIOVASCULAR AND NOCICEPTIVE REFLEXES IN HALOTHANE-ANESTHETIZED RATS, Anesthesia and analgesia, 80(3), 1995, pp. 437-443
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.