Morpho-Histo-Cytological Evaluation of Oral Tissues in Burning Mouth Syndrome: A Systematic Review.

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.