Evidence for the involvement of the mu but not delta opioid receptor subtype in the synergistic interaction between opioid and alpha 2 adrenergic antinociception in the rat spinal cord.
The interaction between the spinal antinociceptive effects of selective mu or delta opioid agonists morphine and DSTBULET (Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr), respectively, and the selective alpha 2 adrenergic agonist dexmedetomidine was examined on convergent dorsal horn neuronal responses in the intact anaesthetized rat. The coadministration of intrathecal morphine (0.5 microgram, 2.5 micrograms) and dexmedetomidine (0.5 microgram) produced a greater than additive inhibition of C fibre-evoked responses. Inhibitions were reversed by either the opioid antagonist naloxone or the alpha 2 adrenergic antagonist atipamezole. The coadministration of intrathecal DSTBULET (1 microgram, 2.5 micrograms) and dexmedetomidine did not result in a supra-additive inhibition of C fibre-evoked responses. The results suggest that mu rather than delta opioid receptors are involved in the synergism of spinal opioid and alpha 2 adrenergic antinociception.
Department of Pharmacology, University College London, UK.
A F
AF
Sullivan
E A
EA
Kalso
H J
HJ
McQuay
A H
AH
Dickenson
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D008297:Male; D008969:Molecular Sequence Data; D009294:Narcotics / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D009294:Narcotics; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C054868:tyrosyl-seryl(O-tert-butyl)-glycyl-phenylalanyl-leucyl-threonine