Effects of intrathecal mu, delta, and kappa agonists on thermally evoked cardiovascular and nociceptive reflexes in halothane-anesthetized rats.
Despite significant opioid binding in the intermediolateral cell column, the effects of intrathecal injections of mu, delta, and kappa opioid agonists on the cardiovascular response to noxious stimulation have not been examined systematically. The pharmacology of intrathecally administered opioid agonists (mu, morphine, [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAGO); delta, metkephamid, [D-Ala2-D-Leu5]enkephalin (DADL), [D-Pen2,D-Pen5]enkephalin (DPDPE); kappa, U50488H and PD117,302) 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 anesthetized with halothane (0.75%) and in which intrathecal catheters had been 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 order of activity being as follows: DAGO > metkephamid DADL > morphine > DPDPE >> nalbuphine = PD117,302 = U50488H = 0. These effects were reversed readily by the opioid antagonist naloxone. In addition, intrathecal administration of mu and delta but not kappa or agonist-antagonist had little effect on resting heart rate and blood pressure. These data indicate that the agonist occupancy of spinal mu and delta, but not kappa agonists can profoundly modulate the autonomic and somatomotor response evoked by high threshold thermal stimuli.
Nagasaka
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Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818.
Yaksh
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TL
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000769:Anesthesia, Inhalation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004744:Enkephalin, Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D006221:Halothane; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009266:Nalbuphine / Q000494:pharmacology; D009619:Nociceptors / Q000502:physiology; D017288:Pain Threshold; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000819:agonists*; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology
D000700:Analgesics; D004745:Enkephalins; D011758:Pyrroles; D011759:Pyrrolidines; D011957:Receptors, Opioid; D013876:Thiophenes; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C054718:PD 117302; D004744:Enkephalin, Methionine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D009266:Nalbuphine; C028208:metkephamid; D006221:Halothane