In recent years, the incidence of neuropathic pain (NP) has been increasing, seriously affecting the life quality of patients. More and more evidence confirms the important role of synaptic plasticity in the pathological mechanism of NP. The structure of dendritic spines is closely related to synaptic function. In this review, we discuss the mechanism and research status in which deformation of dendritic spines regulates NP, including the structure and function of dendritic spines, the role of dendritic spines in spinal cord central sensitization, pain and depression comorbidities. Besides, two molecular signaling pathways as potential therapeutic targets are summarized: Wnt and Rac1 respectively. Exploring and improving the action mechanism of dendritic spines on NP will be beneficial to provide help for clinical treatment.