Temporal Transcriptomic Changes in the Cingulate Cortex of Neuropathic Pain Mice
Neuropathic pain (NP), a debilitating condition from nervous system lesions, is poorly managed by current therapies. The cingulate cortex is crucial for affective pain pro-cessing, yet a comprehensive spatiotemporal understanding of its molecular changes in NP is lacking. This study performed RNA sequencing to profile transcriptomic altera-tions in the anterior (ACC) and midcingulate (MCC) cortices of mice at two and four weeks after spared nerve injury. Bioinformatics analyses, including differential ex-pression, functional enrichment, weighted gene co-expression network analysis, and protein-protein interaction (PPI) network construction, were employed. We identified widespread, time-dependent transcriptional dysregulation in both regions, with dif-ferentially expressed genes increasing over time. Analyses confirmed central roles for synaptic plasticity and neuroinflammatory pathways. Importantly, we uncovered sig-nificant dysregulation in proteostasis and mitochondrial function pathways, mecha-nisms shared with neurodegenerative diseases. PPI analysis identified stage-specific hub genes (e.g., early interferon-stimulated genes and late ribosomal proteins in ACC; persistent extracellular matrix components in MCC). This study provides a detailed transcriptomic atlas of the cingulate cortex in NP, reinforcing known mechanisms while elucidating novel dysregulation in protein homeostasis and mitochondrial pathways. The findings highlight convergent pathophysiology with neurodegenera-tion and offer a new theoretical framework with potential therapeutic targets for chronic NP.