Salivary human mRNA and lncRNA in postmenopausal burning mouth syndrome: Linking inflammation, pain, and comorbidities at the RNA level.

OBJECTIVE: Burning mouth syndrome (BMS), a heterogeneous idiopathic orofacial pain disorder mainly affecting postmenopausal females, is frequently accompanied by anxiety and sleep disturbances. Existing BMS molecular studies have focused primarily on oral bacterial DNA, whereas systematic human salivary transcriptomic profiling remains poorly explored. This study aimed to characterize salivary mRNA and lncRNA signatures in postmenopausal patients with BMS and uncover the transcriptomic mechanisms underlying the pathogenesis of BMS and associated comorbidities. METHODS: Twenty-one patients with BMS and 21 age-matched postmenopausal healthy controls were enrolled. Salivary samples were pooled into three sequencing replicates per group. Whole-transcriptome sequencing was performed to identify differentially expressed RNAs (|log2FoldChange|>1, p < 0.05). GO/KEGG enrichment and lncRNA-mRNA ceRNA network analyses were performed, and core transcripts were validated using RT-qPCR. RESULTS: BMS-associated transcripts were enriched in neuroinflammation, nociceptive sensitization, hormonal signaling, neuronal function, and sleep and emotional regulation. Key hub genes (TLR4, IL1B, PTGS2, FOS) mediate oral neuroinflammatory pain, whereas other transcripts are correlated with BMS-associated comorbidities. NEAT1 and lncRNA105310 form a core inflammation-metabolism ceRNA network, and key changes in expression were experimentally validated. These salivary signatures reflect local oral pathogenesis and systemic physiological and psychological alterations in patients with BMS. CONCLUSIONS: This study establishes a novel salivary transcriptomic profile and ceRNA regulatory network for postmenopausal BMS, providing molecular links between oral neuroinflammatory pain, and hormonal and emotional comorbidities. The non-invasive RNA signatures offer promising auxiliary diagnostic biomarkers and therapeutic targets for BMS, awaiting further prospective cohort validation and refined transcriptomic analyses for clinical translation.