The Burning Pain Transcriptome in the Mouse Primary Somatosensory Cortex

Our previous research has demonstrated that the spinal cord undergoes epigenetic and molecular alterations following non-severe burn injury. However, the primary somatosensory cortex (S1), crucial for pain perception, remains unexplored in this context. Here, we investigated transcriptomic alterations in the S1 cortex of mice subjected to burn injury or formalin treatment, utilizing RNA sequencing (RNA-seq) one hour after injury. RNA-seq identified 1116 differentially expressed genes (DEGs) in burn injury and 136 DEGs in inflammatory pain. Notably, 82.4% of DEGs in burn injury and 32.4% in inflammatory pain were downregulated. A limited number of overlapping DEGs were found, suggesting significant differences in cortical processing of pain with different origins. Gene Ontology Enrichment Analysis revealed that upregulated genes in burn injury were associated with mitochondrial functions and gene expression, whereas downregulated genes were related to axon guidance, synaptic plasticity, and neurotransmission. KEGG pathway analysis highlighted the role of retrograde endocannabinoid signaling in the response to burn injury. Formalin treatment mainly impacted metabolic processes, particularly protein digestion and purine metabolism. These findings demonstrate that transcriptomic remodeling in the S1 cortex is dependent on the sensory modality and suggest that the retrograde endocannabinoid network is activated during the acute pain response following burn injury.