Melatonin is best known as the hormone that tells the body when it is time to sleep. A new review suggests it may also offer some relief from long-lasting muscle and joint pain, particularly when poor sleep is part of the problem.
Researchers combined 23 randomized clinical trials involving 2,028 adults with chronic musculoskeletal pain or pain after surgery. Chronic-pain patients reported lower pain and better sleep, but the improvement was modest, while the postoperative results were far less convincing.
Why sleep and pain are connected
Musculoskeletal pain affects muscles, bones, joints, tendons, and nearby tissues. It includes common conditions such as low back pain, knee osteoarthritis, fibromyalgia, rheumatoid arthritis, and some nerve-related pain.
Sleep and pain can become a stubborn two-way loop. Pain makes rest harder, while poor sleep can increase inflammation and leave the nervous system more sensitive the next day. Melatonin, produced mainly at night by the pineal gland in the brain, may also calm pain pathways, reduce inflammatory activity, and protect cells from oxidative stress.
What the 23 trials found
The University of Sydney team, led by doctoral researcher Kangchao Wu and professor Paulo Ferreira, searched six scientific databases and included only randomized controlled trials. The studies examined chronic conditions as well as recovery from joint replacements, spine procedures, and other musculoskeletal operations.
Across nine chronic-pain trials, melatonin reduced pain by nearly nine points on a 100-point scale when all comparison groups were pooled. In the four trials considered least likely to be biased, the reduction was close to 11 points overall and about 10 points compared with placebo.
There is an important catch. The main analysis did not show a clear advantage over placebo, and some favorable comparisons with pain medicines came from weaker studies. The researchers rated much of the evidence as low certainty and stressed that similar-sized estimates do not prove melatonin works as well as anti-inflammatory drugs.
Better sleep may be part of the effect
The review found that melatonin also improved sleep quality among people with chronic musculoskeletal pain. “For many patients, pain doesn’t exist in isolation and is closely tied to poor sleep,” Wu said.
But the studies cannot yet show who benefits most. Most chronic-pain participants already appeared to have sleep difficulties, yet none of the trials reported separate results for people with and without existing sleep problems.
That leaves a key question unanswered. Does melatonin reduce pain mainly because people sleep better, or does it also act directly on pain signals? Larger trials will need to measure sleep, pain, and daily function separately to find out.
Surgery results tell a different story
Across 12 trials that measured pain after surgery, melatonin produced no meaningful advantage when all comparison treatments were considered together.
Against placebo alone, the average improvement was about 2.5 points on a 100-point scale, far below the roughly 10-point change considered important for patients with acute postoperative pain.
A result can be statistically detectable on paper but still too small for someone recovering from surgery to notice while getting out of bed or trying to sleep comfortably. Melatonin also failed to produce a clear postoperative sleep benefit across the available studies. That is a very different picture from chronic pain.
Dose and safety remain uncertain
The chronic-pain trials used daily doses ranging from 3 to 10 mg., while postoperative studies tested 1 to 10 mg. Researchers found no clear dose-response pattern, so taking more did not consistently produce greater relief.
Longer treatment appeared more helpful for chronic pain, but that clue came from only a small number of studies. Most trials had no follow-up beyond three months, and the average study was relatively small, limiting confidence about lasting benefits and long-term safety.
Reported side effects were generally mild and temporary, including nausea, dizziness, headache, and drowsiness. People with liver or kidney problems, autoimmune diseases, or other medications should speak with a doctor or pharmacist before using melatonin.
An add-on rather than a replacement
The findings do not support replacing established care with melatonin. Exercise, physical therapy, appropriate medication, and treatment of the underlying condition remain central parts of chronic pain management.
Melatonin may eventually sit beside those options for selected patients, especially when pain and insomnia reinforce each other. For now, it looks less like a new painkiller and more like a possible supporting tool, and better trials are needed to determine who should use it, how much to take, and for how long.
Access and oversight also differ by country. In the United States, melatonin is sold as a dietary supplement, and the Food and Drug Administration does not approve supplements for safety and effectiveness before sale. In the United Kingdom, melatonin is available only by prescription.
The full systematic review and meta-analysis was published in the journal PAIN.
