Cytokine’s mechanisms of intervertebral disc degeneration
Degeneration of the intervertebral disc is the major cause of lumbar and radicular pain and is the one of the most common reasons for missed work days. Intervertebral disc alteration is characterized by an elevation of inflammatory cytokines levels: tumor necrosis factor alfa (TNF-α) and interleukins (IL-1 α/β, IL-6 and IL-17) secreted by the disc cells. These cytokines promote extracellular matrix degradation, induce chemokine production and produce cells phenotype changes. The resulting imbalance between catabolic and anabolic responses leads to disc degeneration, herniation of disc material and produce radicular pain. Chemokines released from the degenerated discs promote infiltration and activation of neutrophils, macrophages, T and B cells, and mast cells further amplifying the inflammatory cascade. Migration of immune cells into the disc is accompanied by the development of microvasculature and nerve fibers arising from the dorsal root ganglion (DRG). In this inflammatory milieu, neurogenic factors in particular nerve growth factor (NGF) and brain-derive neurotrophic factor (BDNF) generated by disc and immune cells induce expression of pain associated cation channels in DRGs. Depolarization of these channels is likely to promote discogenic and radicular pain and reinforce the cytokine- mediated degenerative cascade. Complex approach for studying the role of cytokines in the degeneration of the intervertebral disc extracellular matrix will aid revealing the mechanisms and potential targets for therapeutic application in the treatment of patients with degenerative diseases of the spine.