δ-Opioid receptor agonist SNC80 elicits peripheral antinociception via δ1 and δ2 receptors and activation of the L-arginine/nitric oxide/cyclic GMP pathway

In this study, we characterized the role of delta(1) and delta(2), opioids, receptors, as well the involvement of the (L)-arginine/cGMP pathway in the peripheral antinociception induced by delta-opioid receptor agonist (+)-4-[(alpha R)-alpha-((2S,5R)-4-Allyl-2,5-(dimethyl-1-piperazinyl)-3-methoxybenzyl]N,N-diethylbenzamide (SNC80). The paw pressure test was utilized, in which pain sensitivity is increased by intraplantar injection of prostaglandin E-2 (2 mu g). Administration of SNC80 (20, 40 and 80 mu g/paw) decreased the hyperalgesia induced by prostaglandin E, in a dosedependent manner. The possibility that the higher dose of SNC80 (80 mu g) has a central or systemic effect was excluded. since administration of the drug into the contralateral paw did not elicit antinociception in the right paw, 7-Benzylidenenaltrexone (BNTX). 5. 10 and 20 mu g/paw. and 17(Cyclopropylmethyl)-6,7-didehydro-3,14 beta-dihydroxy-4,5 alpha-epoxy-6,7-2',3'-benzo[h]furanomorphinan (naltriben), 2.5. 5 and 10 mu g/paw,81 and 6, opioid receptor antagonist respectively, elicited partial antagonism of the peripheral antinociceptive effect of the SNC80 (80 mu g). The BNTX (10 mu g/paw)-naltriben (5 mu g/paw) combination completely antagonized the peripheral antinociception induced by SNC80 (90 mu g), Further, blockers of the L-arginine./NO/cGMP pathway, N-G-nitro-L-arginine (12, 18 and 24 mu g/paw) and methylene blue (125, 250 and 500 mu g/paw) were observed reverting the peripheral antinociceptive effect of SNC80. This study provides evidence that the peripheral antinociception induced by SNC80 occurs via 61 and 62 receptors and may result from L-arginine./NO/cGMP pathway activation, (c) 2005 Elsevier Inc. All rights reserved.