Activation of spinal delta-1 or delta-2 opioid receptors reduces carrageenan-induced hyperalgesia in the rat.
The role of spinal delta opioid receptors in mediating antinociception was studied by using the carrageenan-induced model of thermal hyperalgesia. Intrathecal administration of [D-Ala2, Glu4]-deltorphin (DELT), a delta-2 receptor agonist, or DPDPE, a delta-1 receptor agonist, produced a dose-dependent increase in paw-flick latency (PFL) with an ED50 of 14.0 micrograms for DELT and 30.4 micrograms for DPDPE. DAMGO, a mu receptor agonist, also increased the PFL in a dose-dependent manner when administered intrathecally with an ED50 of 0.02 microgram. Each opioid agonist increased the PFL to values that exceeded base-line latencies determined before the injection of carrageenan. However, DELT and DPDPE increased the PFL to a greater extent than did DAMGO. Coadministration of 30 micrograms of naltrindole shifted the dose-effect line of DELT to the right by 3.5-fold and that of DPDPE to the right by 2.5-fold, consistent with its characterization as a mixed delta-1/delta-2 receptor antagonist. Coadministration of 3 micrograms of naltriben (NTB) shifted the dose-effect line of DELT to the right by 3.2-fold, whereas 10 micrograms of NTB shifted the dose-effect line of DELT at least 15-fold to the right. Neither dose of NTB antagonized the effects of DPDPE. These data are consistent with characterization of NTB as a selective delta-2 receptor antagonist. The antinociception produced by DAMGO was noncompetitively antagonized by 30 micrograms of naltrindole and it was competitively antagonized by 10 micrograms of NTB. Thus, although NTB distinguishes between delta-1 and delta-2 opioid receptors, high doses may not effectively distinguish between delta and mu receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Stewart
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PE
Department of Anesthesia and Critical Care, University of Chicago, Illinois.
Hammond
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DL
D000818:Animals; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*
D004745:Enkephalins; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C068868:naltrindole benzofuran; C060209:deltorphin II, Ala(2)-; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-; D002351:Carrageenan; C055382:naltrindole