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.
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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 The current body of evidence comprises 1 study and 1 meta-analysis. EvidenceHub rates the overall confidence at 49/100 (low).
The Claim
Melatonin provides modest pain relief in chronic musculoskeletal pain but effects are comparable to conventional analgesics and often below minimal clinically important difference thresholds
This conclusion is most relevant to: Adults with chronic or postoperative musculoskeletal pain.
What the Research Shows
The conclusion draws on 1 linked study. Highlights from the cited literature:
- ▸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) —
How It Works
The proposed biological pathway:
- ▸Melatonin binds to MT1/MT2 receptors
- ▸Modulates circadian rhythm and sleep
- ▸Exerts anti-inflammatory and antioxidant effects
- ▸Result: modest pain reduction and improved sleep quality in chronic MSK pain
Who Might Benefit
Evidence fit by population:
- ▸Adults with chronic or postoperative musculoskeletal pain
Recommended Dose
N/A (dosing varied across studies)
Limitations & Caveats
Important context when interpreting this evidence:
- ▸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.
References
- 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