The Endogenous Cannabinoid System and Nitric Oxide Interact in Modulation of Cold Stress-induced Analgesia

Abstract

The aim of the present study was to estimate 1) whether the endogenous cannabinoid and the nitric oxide-ergic systems' interaction affects cold stress-induced analgesia (c-SIA), and 2) whether the possible interaction (and its impact on c-SIA) differs before and after cold-stress exposure. Male Wistar rats have been injected with CB1-receptor agonist anandamide (AEA) and the nitric oxide (NO) precursor L-arginine before and after 1 hour of cold stress (1 h CS) exposure; CB1 antagonist AM251, the nitric oxide synthase inhibitor L-NAME, and the NO-donor SIN-1 were additionally applied in order to further elucidate the interaction between the two systems. Results obtained suggest that endocannabinoids and NO differently interact before and after stress: applied before stress, the two systems were antagonistic between them with AEA exerting an analgesic effect, while NO decreased analgesia; a synergistic effect of endocannabinoids and NO resulted instead in application after 1 h CS.