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Melatonin is not superior to placebo for reducing pain in chronic musculoskeletal pain but may provide modest benefits as an adjunct treatment

In a systematic review and meta-analysis of 23 studies (2028 participants), melatonin was not superior to placebo for reducing pain in chronic musculoskeletal pain (MD: -6.76/100, 95% CI: -15.89 to 2.36), but sensitivity analysis excluding high-risk studies showed a significant effect (MD: -10.04/100, 95% CI: -17.68 to -2.39). Melatonin improved sleep quality in chronic MSK pain but not in postoperative pain, and adverse events were mild and transient.

Last updated: Jul 8, 2026•0 RCTs•1 Meta-analyses•📖 Read as article →

Evidence Score

Evidence Score49/100
Human RCT☆☆☆☆☆
Meta-analysis★★★☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Efficacy and effectiveness of melatonin for the management of musculoskeletal pain: a systematic review and meta-analysis of placebo and active controlled trials.

observational

Wu K, Ho TH, Beckenkamp PR, Hall M, Zhang H, Puterflam J, Bruun KD, Lin J, Gordon C, Grunstein R, Ferreira ML, Ferreira P · Pain (2026)

Participants: N/A
Duration: N/A (review of studies with variable durations)
Intervention: Melatonin (various doses and formulations) compared to placebo or active controls (e.g., analgesics)
Outcome: Pain intensity (on a 0-100 scale) and sleep quality
Effect Size: MD: -6.76/100 (95% CI: -15.89 to 2.36) for chronic pain vs placebo; MD: -11.21/100 (95% CI: -14.29 to -8.13) vs active controls
Population: People with chronic or postoperative musculoskeletal pain

Result:

PubMed: 42378431DOI: 10.1097/j.pain.0000000000004045

Mechanism Graph

Melatonin binds to MT1/MT2 receptors in the suprachiasmatic nucleus
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Modulates circadian rhythms and sleep-wake cycles
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Exerts anti-inflammatory and antioxidant effects
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Result: Potential reduction in pain perception and improvement in sleep quality

Limitations

  • ⚠Most treatment effect estimates did not reach minimal clinically important difference thresholds
  • ⚠Certainty of evidence was low to moderate due to heterogeneity and risk of bias
  • ⚠Limited evidence for postoperative pain and lack of standardized dosing

Frequently Asked Questions

Is melatonin effective for chronic musculoskeletal pain?▼

Melatonin was not statistically superior to placebo in the main analysis, but sensitivity analysis excluding high-risk studies showed a significant but modest pain reduction. It may be considered as an adjunct rather than primary treatment.

Does melatonin improve sleep in people with musculoskeletal pain?▼

Yes, melatonin improved sleep quality in people with chronic musculoskeletal pain, but not in those with postoperative pain.

How does melatonin compare to conventional analgesics?▼

Melatonin showed similar treatment effect estimates to active controls (e.g., analgesics) but most did not reach clinically meaningful thresholds.

What are the side effects of melatonin for pain management?▼

Adverse events were mild and transient, though specific types were not detailed in the abstract.

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References

  1. 1.Wu K, Ho TH, Beckenkamp PR, Hall M, Zhang H, Puterflam J, Bruun KD, Lin J, Gordon C, Grunstein R, Ferreira ML, Ferreira P. "Efficacy and effectiveness of melatonin for the management of musculoskeletal pain: a systematic review and meta-analysis of placebo and active controlled trials.." Pain, 2026. PMID: 42378431 DOI: 10.1097/j.pain.0000000000004045
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.