Melatonin eases chronic pain, while improving sleep

Clinical takeaway: Melatonin may be a reasonable low-cost adjunct for chronic MSK pain, particularly where poor sleep compounds it; trials most often used 3 mg at bedtime, though no optimal dose has been established.

Melatonin is one of the few interventions positioned to hit the pain-sleep loop from both directions. A meta-analysis of 23 randomized trials found it reduced chronic musculoskeletal (MSK) pain and improved sleep quality, with pain relief comparable in magnitude to standard analgesics. Benefit over placebo held only in the highest-quality trials. Given its cost and safety, the authors frame it as an adjunct, not a replacement.

Pain was measured on a scale from 0 to 100, where higher scores meant worse pain. In chronic MSK pain, melatonin lowered scores by about 10 points versus placebo in the highest-quality trials, after the full pooled analysis had shown no significant separation from placebo.

It also beat active comparators, including NSAIDs and antidepressants. Sleep quality improved by a similar margin. The postoperative picture was weaker: melatonin outperformed placebo but only matched active drugs, and sleep showed no meaningful gain.

The review pooled 23 randomized trials of 2,028 adults with chronic or postoperative MSK pain, drawn from six databases through April 2025. Conditions ranged from low back pain, osteoarthritis, and fibromyalgia to recovery from joint replacement and spinal surgery. Melatonin was compared against placebo, analgesics, and non-analgesic drugs, with a sensitivity analysis restricted to the highest-quality trials.

The open questions are practical ones: the optimal dose, whether benefit holds past three months, and how melatonin performs against analgesics in trials built to minimize bias, since none of the head-to-head comparisons met that bar. Those answers would decide whether it remains a useful adjunct or earns a larger role.

"For many patients, pain doesn't exist in isolation and is closely tied to poor sleep," said Kangchao Wu, a PhD candidate at the Musculoskeletal Research Hub at the University of Sydney's Charles Perkins Centre. "Melatonin appears to target both, which makes it particularly useful for people managing chronic pain."

Source: Wu K, et al. (2026 Jun 30 ) PAIN. Efficacy and effectiveness of melatonin for the management of musculoskeletal pain: a systematic review and meta-analysis of placebo and active controlled trials