Melatonin promotes orofacial antinociception in adult zebrafish by modulating TRP channels

by Selleckchem | Jul 20 2023

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 behaviour 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.

Comments:

The study you described aimed to investigate the involvement of TRP (Transient Receptor Potential) channels in the orofacial antinociceptive (pain-relieving) effect of melatonin in adult zebrafish. The researchers conducted various experiments to assess the effect of melatonin on locomotor activity and orofacial nociception in zebrafish, as well as the interaction between melatonin and TRP channels.

In the study, the researchers first performed an open field test to evaluate the impact of melatonin on the locomotor activity of adult zebrafish. They found that melatonin did not significantly alter the locomotor activity of the animals.

Next, the animals were pre-treated with different concentrations of melatonin (0.1, 0.3, or 1 mg/mL) via gavage (oral administration), and acute orofacial nociception was induced by applying capsaicin (a TRPV1 agonist), cinnamaldehyde (a TRPA1 agonist), or menthol (a TRPM8 agonist) to the animals' lips. The researchers also included naive (untreated) control groups for comparison.

The results showed that melatonin reduced the nociceptive behavior induced by all three agonists. However, the most significant effect was observed with the lowest concentration of melatonin (0.1 mg/mL) in the capsaicin test. This suggests that melatonin has an inhibitory effect on orofacial nociception in zebrafish.

To further investigate the underlying mechanisms, the researchers used specific antagonists for TRP channels. They found that capsazepine (a TRPV1 antagonist) prevented the orofacial antinociceptive effect of melatonin, indicating that the involvement of TRPV1 channels is necessary for melatonin's pain-relieving effect. However, the TRPA1 antagonist HC-030031 did not prevent the antinociceptive effect of melatonin, suggesting that TRPA1 channels may not be directly involved in mediating melatonin's action.

In addition to the experimental findings, the researchers conducted a molecular docking study to assess the interaction between melatonin and TRP channels. The results of the docking study indicated that melatonin interacts with TRPV1, TRPA1, and TRPM8 channels, with a higher affinity observed for TRPV1. These findings align with the in vivo results and support the hypothesis that melatonin's modulation of TRP channels may contribute to its antinociceptive effect in the orofacial region.

In summary, this study provides evidence for the pharmacological relevance of melatonin as an inhibitor of orofacial nociception in adult zebrafish. The results suggest that melatonin's antinociceptive effect is mediated, at least in part, through the modulation of TRP channels, particularly TRPV1. These findings contribute to our understanding of the mechanisms underlying melatonin's analgesic properties and its potential therapeutic applications for orofacial pain management.