Neuropathic pain, a severe type of pain caused by damage or disease affecting the nervous system, impacts millions globally. Recent research highlights the significance of changes in synaptic structure, particularly through the remodeling of dendritic spines, as a key factor in pain development. Dendritic spines are tiny extensions on dendritic branches within the central nervous system (CNS), crucial for forming synaptic connections. Dendritic spines undergo reorganization in various disease or injury models in both superficial and deep layers of the spinal cord dorsal horn, coinciding with the onset of neuropathic pain. Given their role in synaptic communication, focusing on dendritic spines might offer new strategies for treating persistent pain. Recent studies have identified the Rac1-PAK1 pathway, which is essential for the plasticity of dendritic spines, as a potential therapeutic target for pain and neurological disorders. Further exploration of mechanisms underlying the control of dendritic spine plasticity is a promising avenue for developing innovative pain treatments. This chapter focuses on the emerging importance of dendritic spines in neuropathic pain and discusses the prospects of studying dendritic spines to develop new therapeutic approaches.