Spatial transcriptomics uncovers the organization of mouse spinal cord and neuronal subtypes regulating neuropathic pain

The spinal cord integrates diverse somatosensory inputs and coordinates motor outputs through anatomically and functionally segregated circuits. To decode the cellular and circuit organization of such diverse somatosensory and motor functions, we employed spatially resolved single-cell transcriptomic profile of the adult mouse spinal cord. Our results revealed the distinct laminar distributions of spinal cord neurons and non-neuronal cells and distinct regional and sex-specific enrichment of cell subtypes, alluding to the subregion and sex-specificity of several spinal cord functions. We uncovered unique cell-cell communication through ligand-receptor interactions, including neuropeptide and neurotransmitters. Finally, we identified distinct neuronal cell types underlying neuropathic pain, a major healthcare challenge with insufficient molecular understanding. Collectively, this comprehensive molecular and cellular map will facilitate the decoding of the molecular, cellular, and circuit mechanisms underlying somatosensory and motor functions in the spinal cord in health and disease.