Salivary Mucins in Patients with Burning Mouth Syndrome

Abstract

Burning Mouth Syndrome (BMS) is a chronic pain condition that most commonly affects post-menopausal women. Pain is constant or intermittent, ranging from mild to severe. Treatment of BMS remains unsatisfactory, and there is no definitive cure. Mechanisms underlying BMS remain unclear. Evidence of changes in oral mucosal epithelial cells has been found in BMS patients. However, the status of the protective salivary barrier in BMS patients has not been investigated. Salivary mucins represent the first line of defense for oral epithelial cells, and the principal lubricating constituents of saliva. Mucins participate in the formation of the salivary pellicle that covers and protects the oral epithelium. This research is a case-control study that aims to determine whether BMS cases have impaired mucosal barrier function compared to controls without BMS, focusing on the role of mucins as the first line of defense for oral epithelial cells. Our primary aims are to assess: 1) the quantity of MUC1 in unstimulated whole saliva (USWS) in cases and controls; 2) the levels of glycosylation in USWS in cases and controls; and 3) the associations between mucin levels and mucin glycosylation and the severity of oral burning in cases. A total of 50 women (22 BMS cases and 28 healthy controls) age 50 years or older were included in the analysis of this study. Participants attended a clinical visit for salivary sample collection, oral examination, and swab for candida detection and DNA collection. They also completed a pain and health history questionnaire. Total protein concentration was measured using BCA. MUC1 protein was detected and quantified using ELISA. Mucin glycosylation was assessed using dot blots stained with three different lectins (MAL-II, WGA, and UEA). Secretor status was determined by performing targeted candidate gene DNA sequencing of the FUT2 gene. Compared to controls, cases had significantly lower USWS flow rates (p-value <0.001) and had a higher prevalence of xerostomia (p-value=0.001), GI disease (p-value <0.001), and vaginal dryness (p-value=0.01). Cases also consumed a higher number of medications (p-value=0.01). The average salivary protein concentration was 1.30 mg/ml in cases vs. 0.94 mg/ml in controls (p-value= 0.15). Mann Whitney U analysis showed that the levels of MUC1 were lower in cases (n=20, sum of ranks=392.50) compared to controls (n=24, sum of ranks=597.50), p-value=0.17. Although not statistically significant, levels of UEA, MALII, and WGA lectins were lower in cases compared to controls. The percentage of non-secretors was 23% among cases vs. 38% among controls (p-value=0.28). In conclusion, BMS patients had a statistically significant reduction in USWS, higher prevalence of xerostomia, vaginal dryness and GI disease. Underlying pathophysiological mechanisms related to minor salivary gland dysfunction and GI disease should be further investigated.