This review discusses emerging targets in neuroinflammation-driven chronic pain. Current analgesics primarily target pain transduction in neurons but are ineffective in controlling chronic pain. Neuroinflammation, characterized by immune cell infiltration, glial activation, and inflammatory mediator production, plays a key role in chronic pain. Emerging targets include chemokines, proteases, and the Wnt pathway, which promote spinal cord neuroinflammation and chronic pain. Anti-inflammatory and pro-resolution lipid mediators, such as resolvins and protectins, act on immune cells, glial cells, and neurons to resolve neuroinflammation, synaptic plasticity, and pain. Targeting neuroinflammation could offer new therapeutic opportunities for chronic pain and related disorders. Chronic pain affects up to 30% of adults globally and is associated with various types of pain, including inflammatory, cancer, and neuropathic pain. It is characterized by hyperalgesia and allodynia. Chronic pain results from altered neuronal activity, including sensitization of peripheral and central nociceptive neurons. Neuroinflammation is involved in the development and maintenance of chronic pain, and targeting processes and molecules involved in neuroinflammation could lead to better treatments. Neuroinflammation occurs in the peripheral and central nervous systems and is characterized by leukocyte infiltration and increased inflammatory mediator production. Different types of leukocytes infiltrate the CNS at distinct times, with neutrophils first, followed by macrophages and T cells. Glial activation, including microglia, astrocytes, and oligodendrocytes, leads to the production of glial mediators that modulate pain sensitivity. Microglia are the first to respond to peripheral nerve damage, followed by astrocytes. Chemokines, such as CCL2, CXCL1, and CCL7, mediate neuron-glial interactions and are involved in neuropathic pain. CX3CL1 and CX3CR1 mediate neuron-microglia interactions, while CCL2 and CCR2 mediate neuron-microglia and astrocyte-neuron interactions. CXCL1 and CXCR2 mediate astrocyte-neuron interactions and are involved in neuropathic pain. Other chemokines, such as CCL21 and CCL7, are also involved in pain modulation. Emerging targets include pro-resolution lipid mediators, such as resolvins and protectins, which have anti-inflammatory and pro-resolution actions. These mediators, such as RvE1 and protectin D1, inhibit TNF-α signaling and reduce inflammatory pain. They also modulate synaptic plasticity and neuroinflammation, and have potential as therapeutic targets for chronic pain. Proteases, such as matrix metalloproteases (MMPs), cathepsin S, and caspase 6, are involved in neuroinflammation and painThis review discusses emerging targets in neuroinflammation-driven chronic pain. Current analgesics primarily target pain transduction in neurons but are ineffective in controlling chronic pain. Neuroinflammation, characterized by immune cell infiltration, glial activation, and inflammatory mediator production, plays a key role in chronic pain. Emerging targets include chemokines, proteases, and the Wnt pathway, which promote spinal cord neuroinflammation and chronic pain. Anti-inflammatory and pro-resolution lipid mediators, such as resolvins and protectins, act on immune cells, glial cells, and neurons to resolve neuroinflammation, synaptic plasticity, and pain. Targeting neuroinflammation could offer new therapeutic opportunities for chronic pain and related disorders. Chronic pain affects up to 30% of adults globally and is associated with various types of pain, including inflammatory, cancer, and neuropathic pain. It is characterized by hyperalgesia and allodynia. Chronic pain results from altered neuronal activity, including sensitization of peripheral and central nociceptive neurons. Neuroinflammation is involved in the development and maintenance of chronic pain, and targeting processes and molecules involved in neuroinflammation could lead to better treatments. Neuroinflammation occurs in the peripheral and central nervous systems and is characterized by leukocyte infiltration and increased inflammatory mediator production. Different types of leukocytes infiltrate the CNS at distinct times, with neutrophils first, followed by macrophages and T cells. Glial activation, including microglia, astrocytes, and oligodendrocytes, leads to the production of glial mediators that modulate pain sensitivity. Microglia are the first to respond to peripheral nerve damage, followed by astrocytes. Chemokines, such as CCL2, CXCL1, and CCL7, mediate neuron-glial interactions and are involved in neuropathic pain. CX3CL1 and CX3CR1 mediate neuron-microglia interactions, while CCL2 and CCR2 mediate neuron-microglia and astrocyte-neuron interactions. CXCL1 and CXCR2 mediate astrocyte-neuron interactions and are involved in neuropathic pain. Other chemokines, such as CCL21 and CCL7, are also involved in pain modulation. Emerging targets include pro-resolution lipid mediators, such as resolvins and protectins, which have anti-inflammatory and pro-resolution actions. These mediators, such as RvE1 and protectin D1, inhibit TNF-α signaling and reduce inflammatory pain. They also modulate synaptic plasticity and neuroinflammation, and have potential as therapeutic targets for chronic pain. Proteases, such as matrix metalloproteases (MMPs), cathepsin S, and caspase 6, are involved in neuroinflammation and pain