Opioidergic system and second messengers affected the nociceptive effects of Tyr-MIF-1’s after three models of stress

The Tyr-MIF-1 family of neuropeptides (Tyr-MIF-1’s) includes MIF-1, Tyr-MIF-1, Tyr-W-MIF-1 and Tyr-K-MIF-1. Nowadays it is certain that they can modulate pain and some forms of stress-induced analgesia (SIA) by antiopiate and μ-specific processes. The objectives of the present study were twofold: 1) to determine the involvement of opioid system in analgesia induced by immobilization, cold and heat stress (IS, CS and HS); 2) to examine whether opioid system and second messengers are involved in the nociceptive effects of Tyr-MIF-1’s after the three stress models mentioned above. Male Wistar rats were used and nociception was measured by paw-pressure (PP) test. Tyr-MIF-1’s (all in 1 mg/kg), naloxone (Nal, 1 mg/kg) and Methylene Blue (MB, 500 μg/paw) were dissolved in saline and were injected intraperitoneally (i.p.). In the first experimental series Nal was administered 20 min before or immediately after stress procedure. In the second experimental series Nal and MB were administered immediately after stress procedure, 20 min and 60 min, respectively, before the administration of the investigated peptides. The results showed that: (i) opioid and non-opioid components are differently involved in each of stress models. The non-opioid system is mostly involved in CS, opioid – in HS, while both systems are equally presented in IS; (ii) different potency of Tyr-MIF-1’s was observed on immobilization, cold or heat SIA, which may be due to their peptide structure, specific binding sites and different interaction with components of SIA; (iii) opioid system and second messengers are involved in the nociceptive effects of Tyr-MIF-1’s after IS, CS and HS.