Abstract:Neuropathic pain (NP) is a refractory chronic pain condition caused by lesions or diseases of the somatosensory nervous system, characterized by complex pathological mechanisms and limited clinical therapeutic options. In recent years, the emergence of single-cell RNA sequencing (scRNA-seq) has provided a powerful tool to dissect cellular heterogeneity and molecular mechanisms of NP at the single-cell level. This review summarizes the research progress of scRNA-seq in various animal models, including peripheral nerve injury, diabetic neuropathic pain, chemotherapy-induced peripheral neuropathy, and trigeminal neuralgia. It specifically highlights the transcriptomic profiles of neurons, glial cells, and immune cells in the dorsal root ganglia (DRG) and spinal cord, as well as the identification of key pain-related molecules. Furthermore, the roles of cell differentiation trajectories and cell-cell communication networks in the pathogenesis and progression of NP are elucidated. The current status of scRNA-seq studies based on human clinical samples is also introduced to deepen the understanding of NP mechanisms and provide new insights for the discovery of potential therapeutic targets. Currently, this technology still faces challenges such as low cross-species translation efficiency, loss of spatial information, and technical noise. Future research should integrate multi-dimensional "cell-molecule-spatial" data to construct a spatio-temporal dynamic atlas of NP, thereby accelerating the translation of basic research findings into clinical practice.