Research study · Journal of Oral Rehabilitation · 2025
Morpho‐Histo‐Cytological Evaluation of Oral Tissues in Burning Mouth Syndrome: A Systematic Review
Verified on PubMed Oxford CEBM Level 1A: Systematic Review & Meta-Analysis
A 2025 systematic review in Journal of Oral Rehabilitation tested biomarkers in burning mouth syndrome. The results were mixed and the evidence is weak. This review shows that tongue tissue studies point toward nerve changes in burning mouth syndrome, but the studies are small and of low quality, so it does not establish a cause.
In plain language
Study overview
This review looked at tissue samples taken from the mouth of adults with a long-lasting burning mouth condition and compared them with samples from people without it. It pulled together fourteen earlier studies that examined the nerves, surface cells and chemical signals in those samples.
Findings
The results were mixed and the evidence is weak. Several studies found fewer small nerve endings in the tongue of people with the condition, and some found changes in receptors that sense heat and pain, including receptors that respond to cannabis-related chemicals.
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The deeper readScientific analysis
Background: Burning Mouth Syndrome (BMS) is an idiopathic condition characterised by chronic oral burning pain without clinically evident lesions. Despite its prevalence and impact on quality of life, the pathophysiology of BMS remains poorly understood, limiting diagnostic and therapeutic options. Objective: To systematically review histological, morphological and cytological changes in oral tissues of BMS patients, with a focus on epithelial cells and nerve fibres, to identify potential biomarkers and inform future research directions. Methods: A systematic search of electronic databases and grey literature was conducted through October 2024, identifying case-control studies assessing histological or cytological features of oral tissues in adults diagnosed with BMS according to validated criteria. Risk of bias was assessed using the Joanna Briggs Institute tool, and evidence quality was evaluated with GRADE. Results: Fourteen studies involving 214 BMS patients and 130 controls were included. Findings consistently reported reduced epithelial nerve fibre density and increased expression of nociceptive markers such as TRPV1, NGF and P2X3 in BMS tissues. Subepithelial alterations, including increased keratinisation and altered expression of cannabinoid receptors (CB1/CB2), were also observed. Methodological heterogeneity and risk of bias were notable, precluding meta-analysis. The overall quality of evidence was very low. Conclusion: Histological evidence supports neuropathic changes in BMS, involving both neuronal and non-neuronal cells. While these biomarkers hold promise for understanding BMS pathogenesis, standardisation of techniques and further research, including development of animal models, is needed to establish diagnostic and therapeutic utility.
The paper
Citation
Porporatti AL, Schroder ÂGD, Lebel A, Moreau N, Réaux-Le Goazigo A, Taïhi I, et al. Morpho‐Histo‐Cytological Evaluation of Oral Tissues in Burning Mouth Syndrome: A Systematic Review. Journal of Oral Rehabilitation (2025). PubMed 40905465 · DOI
Limitations the authors noted
All included studies were small observational case-control designs with high or unclear risk of bias. Heterogeneous biopsy sites, methods and biomarkers prevented pooling. Confounders such as age, sex and psychosocial status were inconsistently handled. Cannabinoid receptor findings rest on a single small study; no interventional cannabinoid data were reviewed. Histological changes were not correlated with symptom severity across studies.
In practice
Why this matters
This review shows that tongue tissue studies point toward nerve changes in burning mouth syndrome, but the studies are small and of low quality, so it does not establish a cause or a test. It does not show that any cannabis product helps this condition; the cannabis-related finding comes from a single small tissue study and needs far larger, better-controlled research before it can guide care.
Frequently asked questions
Clinical Questions & Answers
What were the primary clinical findings regarding Biomarkers and Burning mouth syndrome?
The results were mixed and the evidence is weak. Several studies found fewer small nerve endings in the tongue of people with the condition, and some found changes in receptors that sense heat and pain, including receptors that respond to cannabis-related chemicals.
What study limitations or clinical safeguards should patients keep in mind?
All included studies were small observational case-control designs with high or unclear risk of bias. Heterogeneous biopsy sites, methods and biomarkers prevented pooling. Confounders such as age, sex and psychosocial status were inconsistently handled.
Browse related research
Condition: Burning mouth syndrome Topic: Biomarkers
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Reviewed by Dr. Caplan on November 1, 2026.
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