Calabrò R.S. et al. - Photobiomodulation and Chronic Orofacial Pain: Evidence Synthesis and Meta-Analyses

In this review of 130 studies, photobiomodulation is the intervention with the most pronounced analgesic effect for burning mouth syndrome, with a reduction in pain in the short term compared with an inactive control. The authors emphasize that the prediction interval crosses the zero value.

What this study measured

Chronic or recurrent orofacial pain encompasses a wide range of conditions: temporomandibular disorders, burning mouth syndrome, trigeminal neuralgia, and other persistent conditions. Complementary approaches are increasingly used to treat these conditions, but comparisons remain inconsistent across diagnoses and assessment criteria.

Rocco Salvatore Calabrò’s team conducted a systematic review of the evidence, supplemented by targeted meta-analyses, registered on PROSPERO under number CRD420251270501 and conducted in accordance with PRISMA 2020. Six databases were searched through December 31, 2025, for randomized and non-randomized studies in adults. Two reviewers selected the articles, assessed the risk of bias, and rated the certainty of evidence (GRADE). A total of 130 studies and 6,879 participants were included. Pain intensity was the primary outcome measure, supplemented by mandibular function, quality of life, and adverse effects.

Key Findings

The most robust finding relates to burning mouth syndrome, characterized by a burning sensation in the oral mucosa without visible lesions.

• Mouth burning, photobiomodulation versus inactive control: standardized mean difference -0.81 (95% CI -1.35 to -0.27), based on 6 trials and 200 participants
• 95% confidence interval: -1.80 to 0.17, thus crossing the zero line
• GRADE certainty: moderate for this outcome
• Other Medications and Supplements for a Burning Sensation in the Mouth: Uncertain Effects
• Temporomandibular disorders: variable effects, low or very low certainty
• Trigeminal Neuralgia and Digital Tools: Limited Data
• Adverse effects not reported in 37 of the 130 included studies

How Photobiomodulation Affects Pain

The mechanism remains hypothetical. Near-infrared light is thought to be absorbed by mitochondrial cytochrome c oxidase, which would increase ATP production in the mucosa and superficial tissues. In burning mouth syndrome, where damage to small nerve fibers is often suggested, this energy supply could support the function of sensory fibers and modulate the release of pain mediators. An effect on local inflammation and on the excitability of nociceptive endings has also been proposed, though this was not verified in this study.

Limits You Should Know

The authors are explicit: a low risk of bias was rare among the included studies. Reporting on function, quality of life, and adverse effects was inconsistent, which limited the statistical pooling. Adverse effects were not reported in 37 of the 130 studies, and the denominators were often imprecise. Non-randomized, narrative studies did not contribute to the pooled estimates. The finding regarding a burning mouth is based on only 6 trials and 200 participants, and long-term follow-up remains rare.

What This Means in Practice

The evidence remains limited: among the options tested for chronic orofacial pain, photobiomodulation stands out as the one with the clearest short-term analgesic effect for burning mouth syndrome, with a level of certainty judged to be moderate. For temporomandibular disorders, results vary depending on the modality and comparator, with low to very low certainty. For trigeminal neuralgia, data are too scarce. The summary provides no information on wavelength, power, or number of sessions.

Frequently Asked Questions

Does photobiomodulation provide relief from burning mouth syndrome?

In this analysis, it is associated with a short-term reduction in pain compared with an inactive control, with a standardized mean difference of -0.81. The certainty is rated as moderate, but the prediction interval crosses the zero value: the result may not be reproducible everywhere.

What about jaw joint pain?

For temporomandibular disorders, the effects vary depending on the technique and the comparator treatment. The certainty of the evidence is generally low or very low, which does not allow for a firm conclusion.

Is this treatment well tolerated?

Adverse effects were not reported in 37 of the 130 included studies, and the denominators were often imprecise. The authors believe that this shortcoming limits the interpretation of the benefit-risk ratio and call for more transparent reporting.

Reference

Calabrò RS, Calderone A, Bonanno L, et al. Advanced, pharmacological, and complementary interventions for chronic or recurrent orofacial pain conditions: a systematic evidence map with selective meta-analyses. The Journal of Headache and Pain, 2026. PMID 41761060. View the study on PubMed

This summary is provided for informational purposes only and does not constitute medical advice. Photobiomodulation is not a substitute for prescribed treatment. Consult a healthcare professional.