ABSTRACT
Melatonin is an endogenous hormone, known as the sleep hormone, which has already demonstrated its antinociceptive effect. This study aimed to evaluate the participation of TRP's channels in the orofacial antinociceptive effect of melatonin (MT) in adult zebrafish. Initially, the open field test was performed to evaluate the effect of MT on the locomotor activity of adult zebrafish. Then, the animals were pre-treated with MT (0.1, 0.3 or 1 mg/mL; gavage) and acute orofacial nociception was induced by the application of capsaicin (TRPV1 agonist), cinnamaldehyde (TRPA1 agonist) or menthol (TRPM8 agonist) applied into the animal's lip. Naive groups were included. MT, per se, did not alter the locomotor activity of the animals. MT reduced the nociceptive behavior induced by the three agonists; however, the most significant effect was obtained with the lowest concentration tested (0.1 mg/mL) in the capsaicin test. The orofacial antinociceptive effect of melatonin was prevented by capsazepine (TRPV1 antagonist), but not by HC-030031 (TRPA1 antagonist). The molecular docking study indicated interaction between MT and the TRPV1, TRPA1 and TRPM8 channels and, in line with the in vivo results, there was greater affinity between MT and the TRPV1 channel. The results confirm the pharmacological relevance of melatonin as an inhibitor of orofacial nociception and this effect seems to be related to the modulation of TRP's channels.
