Transcriptomic insights into ferroptosis and potential therapeutic targets in central Post-Stroke pain following...

Central post-stroke pain (CPSP), affecting nearly one-third of stroke survivors with thalamic lesions, is increasingly linked to ferroptosis due to its established role in neuroinflammatory and neurodegenerative pathologies. This study investigates the molecular mechanisms underlying CPSP induced by thalamic hemorrhage, with a focus on the role of ferroptosis.

Utilizing single-nucleus RNA sequencing and bulk RNA sequencing data from a mouse model of thalamic hemorrhage, we conducted a comprehensive analysis to identify key genes associated with CPSP and ferroptosis. We employed various bioinformatics tools, including gene set enrichment analysis (GSEA), genome-wide association study (GWAS), and Connectivity Map (CMAP) for drug prediction. To validate the key genes and ferroptosis markers identified through bioinformatic prioritization, a CPSP mouse model was established via thalamic collagenase IV injection and assessed using pain behavioral tests, RT-qPCR, and ELISA.

Integrated bioinformatics and experimental analyses identified astrocytic Gja1 as the key contributor to CPSP pathogenesis, showing significant positive correlations with pain severity scores, ferroptosis and immune infiltration levels in thalamic tissues. GWAS analysis confirmed the pathogenic regions of these genes. Additionally, we identified potential therapeutic drugs for CPSP through CMAP analysis.

Our study suggests that astrocytic Gja1 may represent a potential therapeutic target for CPSP, and implicates ferroptosis as a contributing mechanism. These findings provide a preliminary experimental basis for further investigation into targeted interventions and future therapeutic development.