Envolvimento do sistema melatoninérgico na modulação endógena da dor inflamatória e sua participação na analgesia periférica por agonistas opioides e canabinoides

Abstract

Currently, several studies demonstrate the participation of endogenous modulators in the control of peripheral and central pain, including endogenous and endocannabinoid opioid peptides. Melatonin is an important neurohormone involved in several physiological processes such as regulation of the sleep cycle, anxiolytic property, antioxidant, and has recently gainedattained visibility in the area of pain and analgesia. In this context, the aim of this study was to evaluate the possible involvement of the melatonin system in the endogenous modulation of inflammatory pain and its participation in peripheral analgesia by opioid and cannabinoid agonists. The paw compression method was used to assess the nociceptive threshold of male Swiss mice. All drugs were administered in a volume of 20 µL, in a subcutaneous intraplantar injection in the right hind paw of the animals, with hyperalgesia being induced by carrageenan (200 μg/paw). After administration of the melatonin antagonist luzindole at a dose of 200 μg/paw, there was an increase in peripheral nociception caused by carrageenan at different doses. Administration of µ-opioid agonists DAMGO (1 µg/paw), δ-opioid SNC80 (20 µg/paw) and k-opioid Bremazocin (1 µg/paw), as well as the cannabinoid CB1 receptor agonists anandamide (AEA 50 ng/paw) and CB2 PEA (20 µg/paw) were able to induce antinociception. Furthermore, the administration of the melatoninergic antagonist luzindole (100 and 200 µg/paw) partially reversed the antinociception induced by these agonists. Overall, this study provide that melatonin receptors may be involved in the peripheral analgesic mechanism of inflammatory pain control,. In addition, to participating in peripheral antinociception of both opioid and cannabinoid substances, which shows the possibility of a synergism between these systems during the endogenous control event of the nociceptive effect.