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.
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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 The current body of evidence comprises 1 study and 1 meta-analysis. EvidenceHub rates the overall confidence at 49/100 (low).
The Claim
Melatonin is not superior to placebo for reducing pain in chronic musculoskeletal pain but may provide modest benefits as an adjunct treatment
This conclusion is most relevant to: People 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 in the suprachiasmatic nucleus
- ▸Modulates circadian rhythms and sleep-wake cycles
- ▸Exerts anti-inflammatory and antioxidant effects
- ▸Result: Potential reduction in pain perception and improvement in sleep quality
Who Might Benefit
Evidence fit by population:
- ▸People with chronic or postoperative musculoskeletal pain
Recommended Dose
N/A (not standardized across studies)
Limitations & Caveats
Important context when interpreting this evidence:
- ▸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.
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