The article reviews the role of cytokines in the degeneration of intervertebral discs and the resulting pain. Degeneration of the intervertebral disc is a major contributor to back and neck pain, characterized by elevated levels of inflammatory cytokines such as TNF-α, IL-1α/β, IL-6, and IL-17. These cytokines promote matrix degradation, chemokine production, and changes in cell phenotype, leading to an imbalance between catabolic and anabolic responses. The release of chemokines from degenerating discs attracts immune cells like T and B cells, macrophages, neutrophils, and mast cells, further amplifying the inflammatory cascade. The migration of immune cells into the disc is accompanied by the appearance of microvasculature and nerve fibers, which, along with neurogenic factors like NGF and BDNF, induce the expression of pain-associated cation channels in dorsal root ganglion (DRG) neurons. This depolarization of these channels likely promotes discogenic and radicular pain, reinforcing the cytokine-mediated degenerative cascade. The enhanced understanding of the contribution of cytokines and immune cells to catabolic and nociceptive processes provides new targets for treating symptomatic disc disease.The article reviews the role of cytokines in the degeneration of intervertebral discs and the resulting pain. Degeneration of the intervertebral disc is a major contributor to back and neck pain, characterized by elevated levels of inflammatory cytokines such as TNF-α, IL-1α/β, IL-6, and IL-17. These cytokines promote matrix degradation, chemokine production, and changes in cell phenotype, leading to an imbalance between catabolic and anabolic responses. The release of chemokines from degenerating discs attracts immune cells like T and B cells, macrophages, neutrophils, and mast cells, further amplifying the inflammatory cascade. The migration of immune cells into the disc is accompanied by the appearance of microvasculature and nerve fibers, which, along with neurogenic factors like NGF and BDNF, induce the expression of pain-associated cation channels in dorsal root ganglion (DRG) neurons. This depolarization of these channels likely promotes discogenic and radicular pain, reinforcing the cytokine-mediated degenerative cascade. The enhanced understanding of the contribution of cytokines and immune cells to catabolic and nociceptive processes provides new targets for treating symptomatic disc disease.