Temporal Transcriptomic Changes in the Cingulate Cortex of Neuropathic Pain Mice

Background: Neuropathic pain (NP), a debilitating condition from nervous system le-sions, is poorly managed by current therapies. The cingulate cortex is crucial for affec-tive pain processing, yet a comprehensive spatiotemporal understanding of its molec-ular changes in NP is lacking. Methods: This study performed RNA sequencing to pro-file transcriptomic alterations in the anterior cingulate (ACC) and midcingulate (MCC) cortices of mice at two and four weeks after spared nerve injury. Bioinformatics anal-yses, including differential expression, functional enrichment, weighted gene co-expression network analysis, and protein-protein interaction (PPI) network con-struction, were employed. Results: We identified widespread, time-dependent tran-scriptional dysregulation in both regions, with differentially expressed genes increas-ing over time. Analyses confirmed central roles for synaptic plasticity and neuroin-flammatory pathways. Importantly, we uncovered significant dysregulation in prote-ostasis and mitochondrial function pathways, mechanisms shared with neurodegen-erative diseases. PPI analysis identified stage-specific hub genes (e.g., early interfer-on-stimulated genes and late ribosomal proteins in ACC; persistent extracellular ma-trix components in MCC). Conclusions: 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 neurodegeneration and offer a new theo-retical framework with potential therapeutic targets for chronic NP.