Melatonin, the sleep aid tucked into many medicine cabinets, may also have a place in chronic pain care.
A new analysis from the University of Sydney found that melatonin reduced chronic musculoskeletal pain by about nine points on a 0 to 100 pain scale, a result the authors said falls in a similar range to estimates reported for common pain medicines such as opioids, non-steroidal anti-inflammatory drugs and paracetamol. The review, published in PAIN, also found that melatonin improved sleep quality, a notable finding in conditions where pain and poor sleep often feed each other.
For people living with long-lasting back pain, osteoarthritis or fibromyalgia, that combination matters. Musculoskeletal pain affected up to 47 percent of the global population in 2020, according to the paper, and it rarely stays confined to aching joints or a sore back. Poor sleep can make pain feel worse, while pain itself can make it harder to fall asleep or stay asleep.
“Melatonin is already in people’s homes, it’s inexpensive, and we know it’s safe,” said lead author Kangchao Wu, a PhD student at the Musculoskeletal Research Hub in the Charles Perkins Centre and the School of Health Sciences.
“What’s exciting is that melatonin may also help manage chronic pain, opening the door to reducing reliance on medications that come with more risks.”
Melatonin is a hormone produced by the pineal gland and is widely used for sleep problems, though clinical guidelines generally do not recommend it as a first-line treatment for insomnia. Its safety record has helped make it a common choice for short-term sleep support. The Sydney team wanted to know whether that same substance could also help people with musculoskeletal pain, either chronic pain conditions or pain after surgery.
To test that, the researchers conducted a systematic review and meta-analysis of randomized controlled trials. They searched six databases through April 10, 2025, screened 477 titles and abstracts, reviewed 49 full texts and ultimately included 23 trials involving 2,028 participants.
Those studies came from countries including the United States, Russia, Brazil, Egypt, China, Iraq, Turkey, India and Iran. They covered two broad groups: people with chronic musculoskeletal pain, and people recovering from musculoskeletal surgeries such as joint replacement and spinal procedures.
The chronic pain trials included conditions such as low back pain, knee osteoarthritis, fibromyalgia, rheumatoid arthritis, neuropathic pain and temporomandibular disorders. In those studies, melatonin doses ranged from 3 to 10 milligrams per day, with treatment periods from four weeks to three months.
Across nine chronic pain trials, melatonin was linked to a statistically significant reduction in pain compared with all comparator treatments combined. The pooled mean difference was -8.96 on a 0 to 100 scale. Evidence certainty was rated low, in part because of risk of bias and inconsistency between studies.
The picture sharpened when the authors looked only at the four chronic pain studies judged to have low risk of bias. In that sensitivity analysis, pain reduction reached -10.88 points overall, and melatonin also showed a significant benefit over placebo, with a mean difference of -10.04 points.
That result did not mean melatonin outclassed standard pain medicines across the board. Some active-comparator findings came from studies with weaker methods, and the authors said those comparisons should be interpreted cautiously. Still, the pattern was strong enough to suggest that melatonin may deserve consideration as an add-on option, especially in chronic pain settings where sleep problems are part of the picture.
The postoperative findings were different.
In 12 trials of pain after musculoskeletal surgery, melatonin showed no significant benefit compared with all treatments combined. It did beat placebo by a small amount, reducing pain by -2.53 points in the primary analysis, but that fell well short of the paper’s cited minimal clinically important difference of 9.9 points for acute postoperative pain. In other words, the effect may have been measurable, but not large enough for most patients to notice in a meaningful way.
Melatonin also improved sleep quality in chronic musculoskeletal pain, with a pooled mean difference of -11.35 points across seven studies. In postoperative patients, however, no significant sleep benefit emerged when all treatments were considered together.
The appeal of melatonin is not hard to see. In Australia, the paper notes, it costs roughly 0.75 to 1.5 Australian dollars per tablet. The review found no serious adverse events, and the overall rates of side effects were similar to placebo in the studies that reported them.
The most commonly reported problems were nausea or vomiting, dizziness, headache and drowsiness. The authors described melatonin as generally safe for short-term use and pointed to previous reviews showing no evidence of drug dependence or serious adverse events, even with higher-dose or longer-term use.
“For many patients, pain doesn’t exist in isolation and is closely tied to poor sleep,” Mr Wu said. “Melatonin appears to target both, which makes it particularly useful for people managing chronic pain.”
The idea is not that melatonin should replace every existing pain treatment. The paper is more restrained than that. Many pooled effects, while statistically significant, did not clearly reach accepted thresholds for minimal clinical importance in chronic pain populations, which the authors noted often fall around 11 to 14 points on a 0 to 100 scale. They also emphasized that the low certainty of evidence limits how confidently the findings can be applied in routine care.
“Our advice isn’t for melatonin to replace every pain medication,” Mr Wu said. “Instead, after consultation with a doctor, it may be used as an adjunct to existing treatments, particularly for people who also experience sleep problems.”
One practical question remains unsettled: how much melatonin should people take for pain?
Across the chronic pain studies, doses ranged from 3 to 10 milligrams a day. In postoperative studies, they ranged from 1 to 10 milligrams, with regimens varying from a single dose to repeated administration. The authors found no clear dose-response relationship in either chronic or postoperative pain, meaning no single best dose can be recommended from the current evidence.
Longer treatment duration in chronic pain was associated with more favorable effects in exploratory meta-regression, but the authors cautioned that this finding came from a small number of studies. Most trials were also short, and few included follow-up beyond three months.
That leaves several gaps. Many trials had small sample sizes. Study methods and outcome measures varied. The authors could not reliably test whether people with worse baseline sleep problems gained more benefit, and subgroup analyses by pain type were limited by too few studies.
For clinicians and patients, the study offers a cautious but useful signal. Melatonin is inexpensive, familiar and generally well tolerated, and the review suggests it may modestly reduce chronic musculoskeletal pain while also improving sleep. That combination could make it worth discussing in people whose pain and sleep troubles reinforce each other.
The findings do not support using melatonin as a stand-alone substitute for established pain treatments, and they do not make a strong case for postoperative pain. But for chronic musculoskeletal conditions, the evidence points to a possible adjunct that may help reduce dependence on medications with greater risks.
The next step is clearer evidence from larger, higher-quality trials with standardized dosing and longer follow-up.
Research findings are available online in the journal Pain.
The original story “Melatonin may ease chronic pain while improving sleep, study finds” is published in The Brighter Side of News.
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