Intervertebral disc degeneration is a major cause of back and neck pain, characterized by elevated levels of inflammatory cytokines such as TNF-α, IL-1α/β, IL-6, and IL-17, which promote matrix degradation, chemokine production, and cell phenotype changes. These cytokines disrupt the balance between catabolic and anabolic processes, leading to disc herniation and radicular pain. Inflammatory responses are amplified by immune cell infiltration, which also promotes nerve fiber growth and the release of neurotrophic factors like NGF and BDNF, enhancing pain signaling through ion channels in the dorsal root ganglion (DRG). Understanding the role of cytokines and immune cells in disc degeneration provides new therapeutic targets for treating symptomatic disc disease. Inflammatory cytokines such as TNF-α and IL-1 play critical roles in disc degeneration by promoting matrix breakdown, recruiting immune cells, and inducing gene expression for matrix-degrading enzymes. IL-1β is particularly significant, as it is highly expressed in degenerate discs and is more abundant than TNF-α. IL-6 also contributes to disc degeneration by enhancing catabolic processes and inducing TNF-α expression and neuronal apoptosis in the DRG. IL-17 and IFN-γ further exacerbate inflammation and recruit immune cells, contributing to disc degeneration and pain. Inflammatory cytokines and neurotrophins influence pain through changes in nociceptive channel activity and apoptosis in DRG cells. The interplay between these factors is crucial for the development of discogenic and radicular pain. Clinical studies have shown that targeting cytokines such as TNF-α and IL-6 can alleviate symptoms in patients with disc degeneration, herniation, and spinal stenosis. However, the effectiveness of cytokine inhibitors varies, and more research is needed to develop targeted therapies that address the complex regulatory network of cytokines and immune cells in disc disease. Understanding the role of cytokines in disc degeneration, inflammation, and pain is essential for identifying novel therapeutic targets.Intervertebral disc degeneration is a major cause of back and neck pain, characterized by elevated levels of inflammatory cytokines such as TNF-α, IL-1α/β, IL-6, and IL-17, which promote matrix degradation, chemokine production, and cell phenotype changes. These cytokines disrupt the balance between catabolic and anabolic processes, leading to disc herniation and radicular pain. Inflammatory responses are amplified by immune cell infiltration, which also promotes nerve fiber growth and the release of neurotrophic factors like NGF and BDNF, enhancing pain signaling through ion channels in the dorsal root ganglion (DRG). Understanding the role of cytokines and immune cells in disc degeneration provides new therapeutic targets for treating symptomatic disc disease. Inflammatory cytokines such as TNF-α and IL-1 play critical roles in disc degeneration by promoting matrix breakdown, recruiting immune cells, and inducing gene expression for matrix-degrading enzymes. IL-1β is particularly significant, as it is highly expressed in degenerate discs and is more abundant than TNF-α. IL-6 also contributes to disc degeneration by enhancing catabolic processes and inducing TNF-α expression and neuronal apoptosis in the DRG. IL-17 and IFN-γ further exacerbate inflammation and recruit immune cells, contributing to disc degeneration and pain. Inflammatory cytokines and neurotrophins influence pain through changes in nociceptive channel activity and apoptosis in DRG cells. The interplay between these factors is crucial for the development of discogenic and radicular pain. Clinical studies have shown that targeting cytokines such as TNF-α and IL-6 can alleviate symptoms in patients with disc degeneration, herniation, and spinal stenosis. However, the effectiveness of cytokine inhibitors varies, and more research is needed to develop targeted therapies that address the complex regulatory network of cytokines and immune cells in disc disease. Understanding the role of cytokines in disc degeneration, inflammation, and pain is essential for identifying novel therapeutic targets.