Multi-Omics Analysis Reveals Nono-Kcnq2 Regulation of Neuronal Excitability in Neuropathic Pain [scRNA-Seq]

In this study, we employed an integrated multi-omics approach to identify a novel Nono–KCNQ2 regulatory axis that underpins pain progression in chronic constriction injury (CCI) models. Proteomic analysis revealed a marked reduction in potassium ion channel protein expression accompanied by aberrant glutamatergic neuron activation during neuropathic pain progression.

Additionally, phosphoproteomic profiling demonstrated that impaired phosphorylation of these channels—most notably KCNQ2—reduces ion permeability and promotes neuronal hyperexcitability. catTFRE analysis further indicated that diminished Nono transcription factor activity is associated with the downregulation of potassium ion channels in CCI rats. Moreover, single-cell RNA sequencing and spatial transcriptomics localized the co-expression of Nono and Kcnq2 to specific neuronal populations, namely Prph⁺ ventral horn and Nrxn3⁺ dorsal horn neurons, findings that were corroborated by immunofluorescence assays.