Enhanced analgesia: Synergistic effects of melatonin and tramadol on acute thermal nociception in Wistar rats via tail-flick and hot-plate tests

Abstract

Background/aim

The aim of the study is to evaluate the antinociceptive effects of Tramadol+Melatonin [using Hot-plate (HP) and Tail-flick (TF) tests] at the behavioral level and to investigate its effects on motor coordination (using the Rotarod test) in acute pain.

Materials and methods

Thirty-two male Wistar albino rats, 8 weeks old and weighing 250–300 g, were used. The rats were randomly divided into four groups of eight animals each [Control, Tramadol (20 mg/kg), Melatonin (120 mg/kg), and Tramadol+Melatonin (20 mg/kg+120 mg/kg)]. The rats were trained to walk on the rotarod for 3 days prior to the experiment. Thermal acute nociception was assessed in rats using two TF tests and one HP test. Measurements were recorded before drug administration (baseline) and at 15, 30, 60, 90, and 120 minutes post-administration.

Results

Significantly higher values were obtained in both the HP and TF tests compared to the control, Melatonin, and Tramadol groups at various time points. In the Rotarod test, the baseline values of the Melatonin and Tramadol+Melatonin groups were significantly longer at certain post-administration time points.

Conclusion

The findings indicate a potential synergistic interaction between melatonin and tramadol, as evidenced by improved pain sensitivity thresholds. These results underscore the necessity for further clinical investigations to elucidate the therapeutic advantages and underlying mechanisms of this combination. Such research could significantly contribute to the development of more efficacious pain management protocols.