Summary: New research indicates that a common, inexpensive sleep supplement—melatonin—could change how chronic pain is treated. The study found melatonin significantly lowers musculoskeletal pain, producing relief on par with some conventional pain medicines.
Analyzing data from more than 2,000 adults across 23 randomized controlled trials, researchers show melatonin addresses the two-way relationship between sleep disruption and pain. The results point to a widely available, non-addictive adjunct that could be integrated into comprehensive pain management strategies.
Key Facts
- Repurposing a familiar compound: Instead of creating new, costly drugs, this study highlights the value of repurposing melatonin—an affordable compound with a well-established safety profile—for broader use in pain management.
- Average pain reduction: On a 0–100 pain scale, melatonin lowered average pain scores by roughly nine points. The most rigorous trials reported reductions close to 10 points, comparable to relief often seen with NSAIDs and some prescription opioids.
- Dual-action benefits: Chronic pain and sleep disturbance reinforce each other—poor sleep increases pain sensitivity, and pain fragments sleep. Melatonin appears to interrupt this cycle by improving sleep and exerting anti-inflammatory and neuroprotective effects that can reduce pain perception.
- Typical dosing: For chronic musculoskeletal pain, bedtime doses ranged from 3 mg to 10 mg, with 3 mg commonly used. For postoperative pain, doses typically ranged from 1 mg to 10 mg, with 5–6 mg most often reported. The trials did not demonstrate a clear dose-response pattern, so higher doses do not necessarily produce greater benefit.
- Safety profile: Unlike opioids, melatonin shows no risk of chemical dependence or respiratory depression. Mild side effects—such as brief nausea, dizziness, or headaches—occurred at rates similar to placebo over short-term (three-month) study windows.
- Clinical use advice: Researchers stress that melatonin should not replace existing pain treatments on its own. Instead, under medical supervision, it may be a useful adjunct—especially for patients whose pain is worsened by sleep problems.
Source: University of Sydney
A commonly used sleep supplement may reduce reliance on some higher-risk pain medicines, according to new research from the University of Sydney.
Published in the journal PAIN, the analysis found melatonin can reduce chronic musculoskeletal pain by amounts similar to those achieved with some opioids, non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol.
With musculoskeletal conditions affecting a large portion of the global population, these findings point to a low-cost, readily available option that could influence chronic pain treatment approaches.
Melatonin for chronic pain
“Melatonin is already present in many households, it’s inexpensive, and its safety is well documented,” said lead author Kangchao Wu, a PhD student at the Musculoskeletal Research Hub within the Charles Perkins Centre and the School of Health Sciences.
“What’s particularly promising is that melatonin may also help manage chronic pain, offering a path to reduce dependence on medications that carry greater risks.”
The study underscores the practical value of drug repurposing—applying known, well-understood therapies to new clinical problems to deliver faster and more accessible benefits.
“This is a familiar medication being evaluated for a health issue that affects a large share of people worldwide,” said co-author Professor Paulo Ferreira, Director of the Musculoskeletal Research Hub.
Researchers pooled data from 2,028 adults across 23 randomized controlled trials carried out in countries including the United States, Russia, Brazil, Egypt and China. Participants had conditions such as low back pain, osteoarthritis and fibromyalgia, and included patients recovering from procedures like joint replacement and spinal surgery.
Overall, melatonin reduced pain by about nine points on a 0–100 scale, with the more rigorous trials showing reductions near 10 points—an effect size that aligns with commonly used pain medications. The supplement also improved sleep quality, reinforcing the established connection between sleep and pain.
“For many people, pain and poor sleep occur together,” Mr. Wu said. “Melatonin seems to target both problems, making it particularly relevant for those managing chronic pain.”
Across studies, timing and dose varied by condition. For chronic musculoskeletal pain, nightly doses typically ranged from 3 mg to 10 mg, with 3 mg most common. For postoperative settings, doses ranged from 1 mg to 10 mg, most commonly 5–6 mg, usually taken at bedtime or up to an hour before sleep. The evidence did not reveal a single optimal dose.
Safety, side effects and access
Melatonin is generally inexpensive and well tolerated. The most frequently reported side effects were mild nausea, dizziness and headaches; these occurred at similar rates to placebo and no serious adverse events were reported. The trials support safety for short-term use (under three months).
Availability varies by country. In some places melatonin is sold over the counter, while in others it is regulated and may require a prescription. The researchers recommend patients consult their doctor before using melatonin, especially if they are taking other medications or have underlying health conditions.
“We are not recommending melatonin as a wholesale replacement for established pain treatments,” Mr. Wu said. “Rather, after medical consultation, it may serve as a useful, safer adjunct—particularly for patients whose pain is compounded by sleep disturbances.”
As concerns about long-term opioid use and other pain medicines grow, melatonin offers a potentially safer option that could be integrated into care relatively quickly. The researchers note that larger trials would strengthen the evidence base, but current results support cautious, supervised uptake.
“The pain relief we observed is comparable to some conventional treatments, but melatonin should complement—not automatically replace—other therapies,” Mr. Wu added. “It may offer a safer additional option within a broader pain management plan.”
Key Questions Answered:
A: The link lies in the bidirectional relationship between sleep and pain. Chronic pain often disrupts sleep architecture. In turn, sleep loss increases nervous system sensitivity to pain (hyperalgesia). Melatonin helps restore sleep and also has anti-inflammatory and neuroprotective properties. By improving sleep and reducing neural inflammation, it can lower the nervous system’s heightened pain response.
A: No. The researchers caution against abandoning established treatments. Melatonin is best considered an adjunct—a supplementary option to be used under medical guidance. In some cases, successful use of melatonin may allow patients to reduce doses of higher-risk medications, but any changes should be managed by a clinician.
A: In the reviewed trials, melatonin was safe for short-term use (under three months) and showed no evidence of dependence or withdrawal. Minor side effects were rare and matched placebo rates. Access varies internationally—from low-cost over-the-counter products in some countries to prescription-only in others. Patients should consult their physician before adding melatonin to a chronic treatment plan.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full.
- Additional context was added by editorial staff.
About this pain research news
Author: Emily Fraser
Source: University of Sydney
Contact: Emily Fraser – University of Sydney
Image: The image is credited to Neuroscience News
Original Research: Findings published in PAIN