(307) - Identifying single-cell transcriptional changes underlying neuropathic pain in the spinal cord

Abstract

Chronic pain originating from nerve damage affects a substantial number of Americans by impairing daily functions, hindering work performance, and exacerbating quality of life. Peripheral nerve injury gives rise to cellular and molecular changes within the spinal cord. However, cell-specific changes underlying neuropathic pain have not yet been comprehensively studied. Recent advances in single-cell RNA sequencing (scRNAseq) technologies have facilitated the comprehensive characterization of cell types in heterogeneous tissues under normal and pathological states. By employing the scRNAseq technique Drop-Seq, we obtained single-cell transcriptomes from thousands of cells isolated from the mouse spinal cord. Using unsupervised bioinformatic approaches, we clustered cells based on gene expression and identified the principle cell types of the spinal cord based on established marker genes. By applying this technique on the spared nerve injury model of neuropathic pain, we identified transcriptional changes that individual cell types undergo in this chronic pain state. Using this methodology, we determined which cell types are susceptible to dysfunction following peripheral nerve injury and the genes that drive this dysfunction on a cell-specific level. This approach has the potential to identify novel cell-specific pathways that can be targeted to treat neuropathic pain. Research / Grant Support R01NS081127.