Etiology and pathological mechanisms of degenerative disc disease
WU Zong-you
WANG Kai-xiong
KONG Qing-quan
Abstract：Low back pain (LBP), defined as the pain localized between the 12th thoracic rib and the gluteal sulcus, has shown a rising global prevalence, affecting approximately 600 million individuals in 2024, with nonspecific LBP being the most common presentation. Current evidence identifies intervertebral disc degeneration (IVDD) as a primary contributor to nonspecific LBP. IVDD arises from extrinsic factors (acute trauma, repetitive mechanical stress) and intrinsic factors (aging, genetic predisposition, metabolic dysregulation), which triggers inflammatory cascades, extracellular matrix (ECM) degradation (notably proteoglycans and type II collagen), disc dehydration, and mechanical instability. Abnormal innervation, particularly via sinuvertebral nerve ingrowth, further exacerbates chronic pain. Traditional therapies and primarily analgesics alleviate symptoms but fail to halt IVDD progression. Recent advances highlight the roles of inflammation, cellular senescence, oxidative stress, metabolic dysfunction, and autonomic sensitization in IVDD pathogenesis. Emerging interventions, such as senolytics, M2 macrophage polarization, and targeted anti-inflammatory therapies, offer potential to modify IVDD progression. This review synthesizes IVDD etiology, molecular mechanisms, and novel therapeutic strategies, providing a foundation for future research aimed at reversing or halting disc degeneration.
Keywords：Intervertebral disc degenerationLow back painInflammationOxidative stressCellular senescence
Publication Date：2025-07-19
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 577-583 )