Lipid metabolic suppression accompanies an immunometabolic signature in the spinal cord during chronic neuropathic pain.

Chronic neuropathic pain is maintained by persistent spinal cord adaptations, yet the chronic-phase spinal metabolic state and its cross-model reproducibility remain insufficiently defined. Here, we performed GC-MS-based untargeted metabolomics of ipsilateral spinal cord tissue at day 7 after spinal nerve transection (SNT) and integrated these findings with pathway analyses of four independent spinal cord RNA-seq datasets from distinct neuropathic pain models. Metabolomic profiling robustly separated SNT from sham samples and revealed an immune-associated metabolic signature characterized by increased lactic acid, itaconic acid, and glycine, accompanied by broad depletion of GC-MS-detectable free fatty-acid pools. Pathway-level analyses supported coordinated remodeling consistent with inflammatory metabolism alongside reduced lipid-related programs. Across independent RNA-seq datasets, Hallmark GSEA and KEGG pathway analyses (WebGestalt) consistently showed upregulation of immune/inflammatory programs with concomitant downregulation of fatty acid metabolism and cholesterol homeostasis. Together, these multi-omics results define a reproducible chronic-phase spinal signature in which an immunometabolic state accompanies lipid metabolic suppression, providing a cross-model framework for biomarker identification and hypothesis generation in neuropathic pain.