ABSTRACT Herein, we evaluated the involvement of the cannabinoid system in serotonin-mediated peripheral antinociception. After administration of intraplantar prostaglandin E2 (PGE2), animals demonstrating increased pain sensitivity were subjected to a paw pressure test. Serotonin induced a peripheral antinociceptive effect (250 ng); this effect was reversed by the α1-adrenoceptor antagonist prazosin, α2-adrenoceptor antagonist yohimbine, and the β-adrenoceptor antagonist propranolol. Reboxetin amplified the antinociceptive effects of low-dose serotonin. Our data suggest the existence of interactions between the serotonergic and noradrenergic systems during peripheral antinociception.
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