δ-Opioid receptor agonist SNC80 elicits peripheral antinociception via δ1 and δ2 receptors and activation of the l-arginine/nitric oxide/cyclic GMP pathway
Copyright policy )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/NO/cGMP pathway in the peripheral antinociception induced by delta-opioid receptor agonist (+)-4-[(alphaR)-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 microg). Administration of SNC80 (20, 40 and 80 microg/paw) decreased the hyperalgesia induced by prostaglandin E(2) in a dose-dependent manner. The possibility that the higher dose of SNC80 (80 microg) 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 microg/paw, and 17-(Cyclopropylmethyl)-6,7-didehydro-3,14beta-dihydroxy-4,5alpha-epoxy-6,7-2',3'-benzo[b]furanomorphinan (naltriben), 2.5, 5 and 10 microg/paw, delta(1) and delta(2) opioid receptor antagonist respectively, elicited partial antagonism of the peripheral antinociceptive effect of the SNC80 (80 microg). The BNTX (10 microg/paw)-naltriben (5 microg/paw) combination completely antagonized the peripheral antinociception induced by SNC80 (80 microg). Further, blockers of the l-arginine/NO/cGMP pathway, N(G)-nitro-l-arginine (12, 18 and 24 microg/paw) and methylene blue (125, 250 and 500 microg/paw) were observed reverting the peripheral antinociceptive effect of SNC80. This study provides evidence that the peripheral antinociception induced by SNC80 occurs via delta(1) and delta(2) receptors and may result from l-arginine/NO/cGMP pathway activation.
- UNIVERSIDADE DE SAO PAULO Brazil
Male, Analgesics, Arginine, Nitric Oxide, Benzylidene Compounds, Nitroarginine, Dinoprostone, Naltrexone, Piperazines, Rats, Hyperalgesia, Receptors, Opioid, delta, Benzamides, Animals, Enzyme Inhibitors, Nitric Oxide Synthase, Cyclic GMP
Male, Analgesics, Arginine, Nitric Oxide, Benzylidene Compounds, Nitroarginine, Dinoprostone, Naltrexone, Piperazines, Rats, Hyperalgesia, Receptors, Opioid, delta, Benzamides, Animals, Enzyme Inhibitors, Nitric Oxide Synthase, Cyclic GMP
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