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Melatonin is a chemical compound produced by the pineal gland in the brain. Often referred to as the “sleep hormone,” melatonin plays an important role in the circadian rhythm, the 24-hour cycle according to which the sleep and awake states are regulated. Melatonin synthesis increases at night, is inhibited by light,1 and is directly correlated with sleep duration and quality.2 The hormone can be produced synthetically and taken as a supplement; people experiencing sleep disorders such as insomnia and apnea and people trying to ease the effects of jet lag are among those who might take melatonin supplements. However, melatonin also has a lesser-known role in analgesia, also known as pain relief.
The exact mechanisms by which melatonin can provide pain relief are not completely understood, though several possible explanations have been offered. One theory argues that receptors for melatonin in both the central and peripheral nervous systems bind melatonin and thereby block pain signals from transmitting through the nervous system and reaching the brain.3 Another school of thought emphasizes that melatonin has been found to interfere with the ion channels that are critical for the transduction of nerve impulses. A 2013 study showed that melatonin interacts with calcium ion channels, which was sufficient to inhibit abdominal pain caused by psychological stress.4 It is certainly possible that melatonin uses a combination of both mechanisms to relieve pain, or that it may depend on the type of pain or its location within the body.
Melatonin has been found to be effective at reducing pain in a wide variety of contexts. While most of the earlier studies establishing melatonin’s analgesic properties used animal models, clinical trials have established its versatility in this regard. Daily administration of melatonin can reduce chronic inflammatory pain, such as the pain arising from fibromyalgia (a condition characterized by widespread muscle pain, fatigue, and tenderness) and abdominal pain arising from irritable bowel syndrome.3 Experiments with cells that comprise the intervertebral discs of the spine provide encouraging evidence that melatonin could be used to treat intervertebral disc degeneration as well.5
Another area of interest for studying the analgesic properties of melatonin is pain relief from headaches. Headache and sleep are closely related; headaches may cause sleep disturbances and can be a result of sleep disorders, such as obstructive sleep apnea. It might not be so surprising, therefore, that melatonin has been found to effectively lower headache-related pain. In one study, 78.6% of patients who took regular doses of supplementary melatonin experienced relief from headache pain.6 Melatonin has also been successfully used as a prophylactic for migraines; a clinical trial found that 3 mg of melatonin, administered 30 minutes before bedtime, reduced headache intensity, frequency, and duration.7 Finally, because melatonin does not have any adverse effects, it has been suggested that melatonin be used in the perioperative (that is, before surgery) period, to reduce patient anxiety and potentially reduce post-operative pain.8 Further research into the analgesic properties of melatonin – its mechanisms as well as its applications – will enable the medical community to utilize the multiple functions of the compound.
References
1. Zisapel, N. New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation. Br J Pharmacol 175, 3190–3199 (2018), DOI: 10.1111/bph.14116
2. Costello, R. B. et al. The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature. Nutr J 13, 106 (2014), DOI: 10.1186/1475-2891-13-106
3. Xie, S., Fan, W., He, H. & Huang, F. Role of Melatonin in the Regulation of Pain. J Pain Res 13, 331–343 (2020), DOI: 10.2147/JPR.S228577
4. Tan, W., Zhou, W., Luo, H.-S., Liang, C.-B. & Xia, H. The inhibitory effect of melatonin on colonic motility disorders induced by water avoidance stress in rats. Eur Rev Med Pharmacol Sci 17, 3060–3067 (2013), PMID: 24302187
5. Zhang, Y. et al. Melatonin modulates IL-1β-induced extracellular matrix remodeling in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration and inflammation. Aging (Albany NY) 11, 10499–10512 (2019), DOI: 10.18632/aging.102472
6. Rovers, J., Smits, M. & Duffy, J. F. Headache and sleep: also assess circadian rhythm sleep disorders. Headache 54, 175–177 (2014), DOI: 10.1111/head.12217
7. Peres, M. F. P., Zukerman, E., da Cunha Tanuri, F., Moreira, F. R. & Cipolla-Neto, J. Melatonin, 3 mg, is effective for migraine prevention. Neurology 63, 757 (2004), DOI: 10.1212/01.wnl.0000134653.35587.24
8. Chen, W.-W., Zhang, X. & Huang, W.-J. Pain control by melatonin: Physiological and pharmacological effects. Exp Ther Med 12, 1963–1968 (2016), DOI: 10.3892/etm.2016.3565
