The Endogenous Cannabinoid and the Nitricoxidergic Systems Differently Influence Heat and Cold Stress-Induced Analgesia

Abstract

Stress-induced analgesia (SIA) is a well-known phenomenon, in which mechanisms of development opioid and non-opioid components take part. The endogenous cannabinoid system (ECS) takes part in the non-opioid pathways and modulates nociception. Nitric oxide (NO) is also proverbial to interfere with pain perception. The present study was performed to investigate the effects from interaction between the ECS and NO after heat (heat stress) or cold (cold stress) exposure. Male Wistar rats subjected to one hour of heat or cold stress were injected with different combinations of cannabinoid receptor type 1 (CB1) agonist anandamide (AEA) or antagonist (AM251) along with NO-donor, NO-precursor or inhibitor of the NO-synthase (NOS). Nociception was evaluated using Paw pressure (Randall-Selitto) test. The results showed that AEA-administration immediately after the end of stress let to a tendency to increase cold-SIA, but decreased heat-SIA. AEA along with NO-donor increased both cold- and heat-SIA but to a different degree. AM251 and NOS-inhibitor decreased SIA. Our experiments confirmed that the endogenous cannabinoid and the nitricoxidergic systems interact between them in the modulation of SIA. The ECS exerts a more prominent influence on cold rather than heat SIA. Differences in modulation probably depend on the type of stress, due to the different participation of ECS in the mechanisms of SIA development.