Interactions between the endogenous cannabinoid system and the peptides of the Tyr-MIF-1 family modulate heat stress-induced analgesia

Abstract

The present study aimed at evaluating whether an interaction between the endocannabinoid system (ECS) and peptides from the Tyr-MIF-1 family modulates heat stress-induced analgesia. For this purpose, adult male rats were subjected to 1 hour of heat stress. Pain perception was estimated in vivo by Paw pressure test. Immunohistochemical evaluation of CB1 receptors was also performed in the periaqueductal grey (PAG). Our results showed that the application of CB1-receptor agonist anandamide at the end of the stress led to a tendency of decrease in heat-SIA. We also found that each of the four Tyr-MIF-1 peptides interacted with the ECS after acute heat stress, resulting in changes in the PP-thresholds with different direction, degree, and duration. In particular, the administration of MIF-1 and Tyr-K-MIF-1 after CB1-receptor agonist anandamide increased heat stress-induced analgesia (heat-SIA) after the 10th min, while Tyr-MIF-1 and Tyr-W-MIF-1 produced only short-lasting analgesia. CB1-expression in the PAG was also estimated, showing an increase after Tyr-MIF-1 and Tyr-W-MIF-1 administration with anandamide pretreatment, and a decrease after Tyr-W-MIF-1 administration with the CB1-receptor antagonist AM251- or the opioid receptor antagonist naloxone pretreatment. In summary, it can be inferred that under heat stress conditions the peptides from the Tyr-MIF-1 family, interacting with opioid and non-opioid receptors, differently relate with the cannabinoid system and such an interaction modulates heat stress-induced analgesia. It also seems that Tyr-MIF-1 and Tyr-W-MIF-1 have a direct impact on CB1-expression in the PAG, while MIF-1 and Tyr-K-MIF-1 probably act via second messengers or the activation of additional neurotransmitter system(s).