The antinociceptive role of mu- and delta-opiate receptors and their interactions in the spinal dorsal horn of cats.
This study was undertaken to examine the antinociceptive roles of different subtypes of opiate receptors and their interactions at the level of the spinal cord. We recorded extracellularly the activity of the single wide dynamic range neurons evoked by noxious radiant heat (51 degrees C) in decerebrate, spinally transected cats. The separate intrathecal administration of DAGO selective mu-agonist, n = 28), morphine (less selective mu-agonist, n = 22), DPDPE (selective delta-agonist, n = 25), and DADL (less selective delta-agonist, n = 17) produced statistically significant suppression of noxiously evoked activity in a time- and dose-dependent manner. In addition, intravenously administered naloxone (nonselective opiate antagonist) reversed the suppressive effects of all opiates studied. Intravenously administered ICI 174,864 (selective delta-antagonist) reversed the effects of DPDPE. These results, based on relative selectivity for opiate receptors, indicate that both mu- and delta-opiate receptors can modulate the input of nociceptive information in the spinal dorsal horn. To study interactions between mu- and delta-receptors at the level of the spinal cord, a combination of the above agonists was injected intrathecally--namely, an ineffective or slightly effective dose of DAGO (1 or 1.5 micrograms, respectively) that was combined with an ineffective dose of DPDPE (30 micrograms). The intrathecal combination of DAGO and DPDPE produced significant synergistic suppressive effects of noxiously evoked activity. These findings, again based on relative selectivity, suggest that drug combinations that include both selective mu- and delta-agonists may be a useful method of lowering the total amount of any one drug, thus decreasing the likelihood of side effects, while at the same time producing significant analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Omote
K
K
Department of Anesthesiology, Yale University, New Haven, Connecticut 06510.
Kitahata
L M
LM
Collins
J G
JG
Nakatani
K
K
Nakagawa
I
I
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects*; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D000701:Analgesics, Opioid; D004745:Enkephalins; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine