Activation of spinal delta-1 or delta-2 opioid receptors reduces carrageenan-induced hyperalgesia in the rat
Stewart, P.E.; Hammond, D.L.
Journal of Pharmacology and Experimental Therapeutics 268(2): 701-708
1994
ISSN/ISBN: 0022-3565 PMID: 8113981 Document Number: 426833
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-Ala-2, Glu-4)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 ED-50 of 14.0 mu-g for DELT and 30.4 mu-g for DPDPE. DAMGO, a mu receptor agonist, also increased the PFL in a dose-dependent manner when administered intrathecally with an ED-50 of 0.02 mu-g. 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 mu-g 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 mu-g of naltriben (NTB) shifted the dose-effect line of DELT to the right by 3.2-fold, whereas 10 mu-g 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 mu-g of naltrindole and it was competitively antagonized by 10 mu-g 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. Alternatively, this finding may suggest an interaction between spinal delta-2 and mu opioid receptors. Taken together, these results indicate that activation of either delta-1 or delta-2 opioid receptors in the rat spinal cord results in antinociception and that delta receptors may play a more prominent role than mu receptors in the production of antinociception in this model of thermal hyperalgesia.