Role of exogenous and endogenous melatonin in rem sleep restriction-induced pain model

Background and Aim: Although the relationship between sleep loss and pain is known for a long time, the underlying mechanism has not yet been fully elucidated. the aim of this study is to demonstrate increase the role of exogenous and endogenous melatonin on hyperalgesia induced by sleep restriction. Material and Methods: In the first part of the study, 28 male Sprague Dawley rats subjected to baseline pain measurements (tail flick and hot plate) and then divided into four groups (n=7). While 3 groups were subjected to 8 hours of REM sleep restriction per day for 15 days, the control group continued to maintain normal sleep schedule. One of the groups subjected to REM sleep restriction received melatonin 5 mg/kg i.p. every day at 17:00. The other groups received melatonin solvent 5% dimethyl sulfoxide (DMSO) i.p. for the same period. The third sleep restriction group received no treatment. Pain measurement were repeated every other day. At the end of the period, the animals were sacrificed and tissue samples were taken from the posterior part of the spinal cord lumbar region and tissue noradrenaline and serotonin measurements were made with LC-MS/MS. The pineal glands of 18 mice were surgically removed in the second part of the study. Serum melatonin levels were measured before pinealectomy and on postoperative day 7. Pain behaviour was evaluated before and 14 days after pinealectomy. Here, 2 subgroups were randomly formed and one group was given melatonin 5 mg/kg i.p. and the other 5% DMSO i.p. single dose and pain measurements were repeated 1 hour later. Results: In the first part, pain latency decreased in the tail-flick test in the sleep restriction groups that were given no medication (6.3±0.3sec) and DMSO (6.0±0.9sec), while this decrease was not observed in the melatonin groups (11.7±0.5sec) and the control group that slept normally (11.5±0.9sec) (p<0.01). There was no significant difference between the groups in the posterior horn noradrenaline and serotonin levels. In the second part, the pain level decreased significantly after pinealectomy. While the pain level in the exogenous single-dose melatonin group increased, there was no change in the DMSO group. Conclusion: These findings suggest that inadequate endogenous melatonin secretion may play a role in the decrease in pain threshold due to sleep loss and that this deficiency can be compensated by exogenous melatonin. The fact that pinealectomy reduces the pain threshold suggests that endogenous melatonin acts as a kind of analgesic system in pain control.