This review focuses on emerging targets in neuroinflammation-driven chronic pain, highlighting the role of chemokines, proteases, and the Wnt pathway in promoting spinal cord neuroinflammation and chronic pain. It also discusses anti-inflammatory and pro-resolution lipid mediators that act on immune cells, glial cells, and neurons to resolve neuroinflammation, synaptic plasticity, and pain. Targeting excessive neuroinflammation offers new therapeutic opportunities for chronic pain and related neurological and psychiatric disorders. The review emphasizes the importance of understanding the distinct characteristics of activated glial cells and the role of chemokines in mediating neuron-glial interactions. Additionally, it explores the potential of pro-resolution lipid mediators (PRLMs) such as resolvins and protectins, which have potent anti-inflammatory and neuroprotective actions. The review also discusses other emerging targets, including proteases and the Wnt signaling pathway, and their potential in treating chronic pain.This review focuses on emerging targets in neuroinflammation-driven chronic pain, highlighting the role of chemokines, proteases, and the Wnt pathway in promoting spinal cord neuroinflammation and chronic pain. It also discusses anti-inflammatory and pro-resolution lipid mediators that act on immune cells, glial cells, and neurons to resolve neuroinflammation, synaptic plasticity, and pain. Targeting excessive neuroinflammation offers new therapeutic opportunities for chronic pain and related neurological and psychiatric disorders. The review emphasizes the importance of understanding the distinct characteristics of activated glial cells and the role of chemokines in mediating neuron-glial interactions. Additionally, it explores the potential of pro-resolution lipid mediators (PRLMs) such as resolvins and protectins, which have potent anti-inflammatory and neuroprotective actions. The review also discusses other emerging targets, including proteases and the Wnt signaling pathway, and their potential in treating chronic pain.