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Melatonin provides modest pain relief in chronic musculoskeletal pain but effects are comparable to conventional analgesics and often below minimal clinically important difference thresholds

In a systematic review of 23 RCTs (2028 participants), melatonin was not superior to placebo for chronic MSK pain (MD: -6.76/100, 95% CI: -15.89 to 2.36) but was superior to active controls (MD: -11.21/100, 95% CI: -14.29 to -8.13). Sensitivity analysis limited to low-risk studies showed superiority over placebo (MD: -10.04, 95% CI: -17.68 to -2.39). Sleep quality improved in chronic MSK pain but not postoperative pain, and adverse events were mild and transient.

Last updated: Jul 7, 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
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Modulates circadian rhythm and sleep
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Exerts anti-inflammatory and antioxidant effects
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Result: modest pain reduction and improved sleep quality in chronic MSK pain

Limitations

  • ⚠Most treatment effects did not reach minimal clinically important difference thresholds
  • ⚠Certainty of evidence was low to moderate
  • ⚠Limited evidence for postoperative pain

Frequently Asked Questions

Is melatonin effective for chronic musculoskeletal pain?▼

Melatonin shows modest pain relief in chronic MSK pain, but effects are often below clinically meaningful thresholds and comparable to conventional analgesics.

Does melatonin improve sleep in people with musculoskeletal pain?▼

Yes, sleep quality favored melatonin in people with chronic MSK pain, but not in those with postoperative pain.

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

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

Should melatonin be used as a primary treatment for musculoskeletal pain?▼

No, the authors suggest melatonin may be considered as a potential adjunct rather than a primary treatment, pending more research with standardized dosing and longer follow-ups.

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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.