CircRNA expression profiling of the rat thalamus in temporomandibular joint chronic inflammatory pain

Abstract

Orofacial pain (OFP) induced by temporomandibular disorders (TMDs) is prevalent, affecting approximately 4.6 % of the population. One specific type of TMD is temporomandibular osteoarthritis (TMJOA), a common degenerative disease that significantly impacts patients' quality of life. Differentially expressed circular RNAs (DEcircRNAs) in the thalamus, which serves as a relay station in the orofacial pain transmission pathway, may play a crucial role and serve as potential target markers for inflammation and the progression of inflammatory pain in TMJOA. The aim of this study was to investigate the expression profile of circRNAs in the thalamus of TMJOA. We obtained the circRNA expression profile from the thalamus of a rat model of TMJOA through high-throughput sequencing (HT-seq) and further validated their expression using reverse transcription real-time polymerase chain reaction (RT-qPCR), followed by bioinformatics analysis of the expression data. A total of 425 circRNAs (DESeq2 p- value < 0.05, |log2FoldChange| > 0.0) were identified as significantly differentially expressed by RNA-Seq, comprising 188 up-regulated and 237 down-regulated circRNAs. After validation via RT-qPCR, we employed miRanda software to predict the binding sites of miRNAs for the identified circRNAs to further explore the functions of DEcircRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that DEcircRNAs were primarily enriched in pathways and functions related to synapse development, protein signaling and modification, 'Circadian entertainment', the 'MAPK signaling pathway', and 'Glutamatergic synapse'. These findings suggest that DEcircRNAs in the thalamus play a significant role in the progression of TMJOA and may serve as promising candidate molecular targets for gene therapy.

Keywords: Central sensitization; Chronic inflammatory pain; CircRNA; TMJOA; Thalamus.