Delta receptor involvement in morphine suppression of noxiously evoked activity of spinal WDR neurons in cats.
Morphine has been considered to be primarily a mu opiate receptor agonist. The present study was designed to determine if opiate receptor subtypes in addition to mu contribute to morphine analgesia at the level of the spinal cord. Extracellular activity of single wide dynamic range (WDR) neurons in the feline lumbar spinal cord were studied. Intrathecal administration of DAGO (selective mu agonist) or DPDPE (selective delta agonist) suppressed the noxiously (51 degrees C radiant heat) evoked activity of WDR neurons. Pretreatment with spinal beta-FNA (selective mu antagonist) antagonized the suppressive effects of spinal DAGO, but not that of DPDPE. Two doses of spinal morphine (200 and 400 micrograms) suppressed the noxiously evoked activity of WDR neurons confirming our previous report. Following beta-FNA pretreatment, the suppressive effects of morphine were reduced, however, when ICI 174,864 (selective delta antagonist) was co-administered with morphine on the spinal cord of the animals pretreated by beta-FNA, there was an even greater reduction in the neuronal suppression by morphine. Intravenous ICI 174,864 also reversed the suppressive effects of morphine in beta-FNA pretreated animals. beta-FNA antagonism of spinal morphine is evidence of the well-known mu receptor-mediating antinociception. However, antagonism by ICI 174,864 of morphine suppression in beta-FNA-pretreated animals demonstrates that morphine is capable of suppressing noxiously evoked activity of WDR neurons as a result of an interaction with delta receptors in addition to mu receptors at the level of spinal cord.
Omote
K
K
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510.
Kitahata
L M
LM
Nakatani
K
K
Collins
J G
JG
D000698:Analgesia; D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D004745:Enkephalins; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine