# Morpho‐Histo‐Cytological Evaluation of Oral Tissues in Burning Mouth Syndrome: A Systematic Review

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/research/biomarkers-for-burning-mouth-syndrome-systematic-review/
> **Published:** 2026-11-01T11:15:12-04:00 | **Last Modified / Clinically Audited:** 2026-11-02T06:30:42-04:00
> **Clinical Summary:** 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.

---

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.

 

### Related

---

### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House).
- **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`).
- **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/).
- **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637).
- **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).