Unraveling the mechanisms of intervertebral disc degeneration: an exploration of the p38 MAPK signaling pathway

Intervertebral disc (IVD) degeneration (IDD) is a worldwide spinal degenerative disease and a major cause of low back pain (LBP), leading to significant personal and societal burdens. IDD arises from complex factors including senescence, genetics, and trauma, with resulting dysfunction linked to extracellular matrix (ECM) degradation, cellular differentiation, inflammation, oxidative stress, mechanical stress, and senescence. Current IDD treatments largely alleviate symptoms without addressing underlying pathophysiology. The p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway participates in key processes of IDD, including inflammation, ECM degradation, apoptosis, senescence, proliferation, oxidative stress, and autophagy, all of which contribute to degeneration. Thus, p38 MAPK represents a promising therapeutic target. This review summarizes how p38 MAPK governs pathophysiological alterations in IVD during IDD and outlines potential avenues for targeted therapies.