Background
Smoking is a major modifiable risk factor for low back pain and intervertebral disc degeneration (IVDD), yet the mechanisms linking tobacco exposure to disc failure remain incompletely defined. Evidence suggests that smoking impairs disc nutrition and matrix homeostasis while reshaping the nucleus pulposus (NP) microenvironment through immune infiltration and altered cellular states.
Methods
We performed a narrative synthesis of experimental, clinical, and translational studies on smoking and disc biology, integrating our mechanistic work on smoking-induced mast cell activation and single-cell transcriptomic profiling of human degenerative NP tissues.
Results
Smoking accelerates IVDD through converging mechanisms. First, it impairs vertebral endplate microcirculation, reducing oxygen and nutrient diffusion to the avascular disc and disrupting NP homeostasis. Second, nicotine and smoke-related mediators promote pathological angiogenesis and inflammatory signaling by enhancing endothelial activation, vascular endothelial growth factor expression, and matrix metalloproteinase activity. Third, smoking induces proteoglycan loss, matrix degradation, DNA damage, and cellular senescence in disc cells. Our prior work demonstrated that smoking activates mast cells, leading to tetramer tryptase release, METTL14-mediated changes, and accelerated NP degeneration. Single-cell transcriptomic data reveal cellular heterogeneity in degenerative NP, including fibroblast-like NP cells, CD90-positive progenitor-like NP cells, and infiltrating immune populations such as granulocytic myeloid-derived suppressor cells. These findings support the concept that smoking acts on a multicellular disc ecosystem rather than NP cells alone. Neutrophil-related matrikine pathways, including Pro-Gly-Pro and N-acetylated Pro-Gly-Pro, may amplify persistent inflammation and matrix breakdown.
Conclusions
Smoking drives IVDD through vascular compromise, inflammatory cell recruitment, aberrant angiogenesis, and degeneration-associated NP reprogramming. A multicellular ecosystem framework may better explain smoking-related chronic disc degeneration and pain. Targeting mast cell signaling, neutrophil-associated matrikines, and degeneration-related NP subpopulations may offer new therapeutic strategies, while smoking cessation remains critical for spine health preservation.