Patients with peripheral nerve injury, viral infection or metabolic disorder often suffer neuropathic pain due to inadequate pharmacological options for relief. Developing novel therapies has been challenged by incomplete mechanistic understanding of the cellular microenvironment in sensory nerve that trigger the emergence and persistence of pain. In this study, we report a high resolution transcriptomics map of the cellular heterogeneity of naïve and injured rat sensory nerve covering more than 110,000 individual cells. Annotation reveals distinguishing molecular features of multiple major cell types totaling 45 different subtypes in naïve nerve and an additional 23 subtypes emerging after injury. Ligand-receptor analysis revealed a myriad of potential targets for pharmacological intervention. This work forms a comprehensive resource and unprecedented window into the cellular milieu underlying neuropathic pain and demonstrates that nerve injury is a dynamic process orchestrated by multiple cell types in both the endoneurial and epineurial nerve compartments.

Rxrg, Grin2b, Fxyd7, Ninj2, Scn7a, Gpr83, Dusp10, Tmem196, Ngfr, Bdnf, Erbb3, Sox2, Pdgfra, Dpp4, Ptges, Ptgs2, Cxcl1, Irf1, Gdf10, BMP4
Bmper, FGF10, Fbln2, Eln, Col8a1, Ogn, Sox8, Bmp7, Igsf345, Fgf2r39, Ptprn, Acta2, Des, Tnc, Cxcl6, Pdgfra, Tnfsf13b, Cxcl12, CCL7, Mmp11
Mmp14, Col8a1, Col11a1, Cilp, RT1, Cd163, Ccl7, Ccl24, Ccl2, Cxcl1, Cxcl2, Ccl4, Anxa3, Ifngr1, Cxcl16, Igfbp3