Whole-transcriptome sequencing analysis of spinal neuronal ferroptosis in aggravating neuropathic pain

Neuropathic pain triggered by peripheral nerve injury (PNI) poses substantial therapeutic difficulties. Emerging evidence highlights the involvement of ferroptosis in spinal neurons during PNI-associated pain progression, yet the precise molecular pathways governing this process remain elusive. This study obtained a comprehensive expression profile using whole-transcriptome sequencing within neuronal ferroptosis model. Whole-transcriptome sequencing identified Mgst1, Nqo1, Srxn1, Pgd, and Slc2a1 as the key differentially expressed genes implicated in neuronal ferroptosis, with particular emphasis on the Hippo signaling pathway, PPAR signaling pathway, and histone modification in the regulation of ferroptosis phenotype. The competitive endogenous RNA (ceRNA) network was constructed via mRNAs, miRNAs, lncRNAs and circRNAs profiling, with lncRNA-Sh3bp5l/miR-92b-5p/PGD and lncRNA-Scrn2/miR-133a-3p/SRXN1 regulatory axes functionally validated. Intervention of SRXN1 and PGD expression suppressed neuronal ferroptosis in the spinal cord dorsal horn, and this process alleviated chronic constriction injury (CCI)-induced neuropathic pain. Collectively, we identified ferroptosis-related genes, signaling pathways, and ceRNA regulatory axes in PNI-induced neuropathic pain, which may represent molecule mechanisms and therapeutic targets underlying the exacerbation of spinal neuronal ferroptosis and neuropathic pain.