A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects.
Study Goal
The researchers aimed to evaluate the dose-dependent analgesic effects of sublingual melatonin on pressure and heat pain thresholds and tolerance, as well as its sedative effects in healthy humans.
Results Summary
The study found that melatonin produced significant, dose-dependent antinociceptive effects, with higher doses (0.15 mg/kg and 0.25 mg/kg) showing greater pain threshold and tolerance improvements compared to placebo. Serum melatonin levels correlated linearly with pain modulation, supporting its potential as an analgesic agent.
Population
61 healthy subjects aged 19 to 47 years.
Effective Dosage
0.05 mg/kg, 0.15 mg/kg, and 0.25 mg/kg sublingual melatonin (single dose).
Duration
Single-dose intervention (duration not specified).
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
sublingual melatonin | increase | antinociceptive activity | healthy subjects aged 19 to 47 y | dose-dependent | exerts well-defined dose-dependent antinociceptive activity | #1 |
sublingual melatonin | increase | pain threshold | healthy subjects aged 19 to 47 y | - | significant differences between the placebo vs. the intermediate (0.15 mg/kg) and the highest (0.25 mg/kg) melatonin doses | #2 |
sublingual melatonin | increase | sedation level | healthy subjects aged 19 to 47 y | - | significant differences between the placebo vs. the intermediate (0.15 mg/kg) and the highest (0.25 mg/kg) melatonin doses | #3 |
sublingual melatonin | increase | heat pain threshold (HPT) | healthy subjects aged 19 to 47 y | R(2) = 0.492 | significant association between the serum melatonin concentrations and changes | #4 |
sublingual melatonin | increase | pressure pain threshold (PPT) | healthy subjects aged 19 to 47 y | R(2) = 0.538 | significant association between the serum melatonin concentrations and changes | #5 |
sublingual melatonin | increase | heat pain tolerance (HPTo) | healthy subjects aged 19 to 47 y | R(2) = 0.558 | significant association between the serum melatonin concentrations and changes | #6 |
sublingual melatonin | increase | pressure pain tolerance (PPTo) | healthy subjects aged 19 to 47 y | R(2) = 0.584 | significant association between the serum melatonin concentrations and changes | #7 |
sublingual melatonin | increase | pain threshold | healthy subjects aged 19 to 47 y | - | correlation between the plasma melatonin drug concentration and acute changes | #8 |
BACKGROUND: Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modulation. OBJECTIVE: The objective was to evaluate the analgesic dose response of the effects of melatonin on pressure and heat pain threshold and tolerance and the sedative effects. METHODS: Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold (PPT) and the pressure pain tolerance (PPTo). Quantitative sensory testing (QST) was used to measure the heat pain threshold (HPT) and the heat pain tolerance (HPTo). Sedation was assessed with a visual analogue scale and bispectral analysis. RESULTS: Serum plasma melatonin levels were directly proportional to the melatonin doses given to each subject. We observed a significant effect associated with dose group. Post hoc analysis indicated significant differences between the placebo vs. the intermediate (0.15 mg/kg) and the highest (0.25 mg/kg) melatonin doses for all pain threshold and sedation level tests. A linear regression model indicated a significant association between the serum melatonin concentrations and changes in pain threshold and pain tolerance (R(2) = 0.492 for HPT, R(2) = 0.538 for PPT, R(2) = 0.558 for HPTo and R(2) = 0.584 for PPTo). CONCLUSIONS: The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent. Brazilian Clinical Trials Registry (ReBec): (U1111-1123-5109). IRB: Research Ethics Committee at the Hospital de Clínicas de Porto Alegre.