BackgroundThe thalamus is one of the structures that receives projections from multiple ascending pain pathways. Although the transmission of orofacial and somatic pain involves different nuclear clusters and nerve pathways, the thalamic neuroimmune alterations across these different pain modalities remain poorly understood. This work aimed to investigate alterations in the neuroimmune mechanisms of the thalamus under chronic orofacial and somatic inflammatory pain conditions via bioinformatics analysis and to identify novel therapeutic targets for chronic pain management.MethodsTo illuminate the potential molecular mechanisms in inflammatory pain, we compared thalamic mRNA expression levels between Complete Freund’s Adjuvant (CFA) induced chronic orofacial pain and somatic inflammatory pain in rats. Bioinformatic analyses were conducted to determine functional pathway enrichment and protein–protein network analyses.ResultsThe overlapping of differentially expressed genes (DEGs) between chronic orofacial pain and plantar pain included 13 genes. Gene Ontology (GO) analysis revealed that the DEGs were mainly related to inflammatory response, immune system process, and cytokine activity. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted a prominent enrichment in the IL-17 signaling pathway. The RT-qPCR was used to identify the mRNA expressions of DEGs in the thalamus of rats with chronic orofacial and plantar inflammatory pain, thereby validating our analytical results.ConclusionOur study identified candidate hub genes that are associated with the pathogenesis of chronic orofacial and somatic inflammatory pain in the thalamus, which provides preliminary insights into potential alterations in immune mechanisms within the thalamus under different pain conditions.