Cytokines, Neuroplasticity Modulators, and Biomarkers in Spinal Canal Stenosis and Endoscopic Decompression

Research Rationale and Study Design Lumbar spinal stenosis (LSS) is a common degenerative musculoskeletal disorder characterized by narrowing of the spinal canal, often leading to pain and disability. One of the primary contributors to this condition is hypertrophy (thickening) of the ligamentum flavum (LF), along with facet joint degeneration, intervertebral disc herniation, and ligament ossification. However, the pathophysiological mechanisms behind these changes remain incompletely understood. Histological changes in hypertrophied LF include fibrocartilaginous metaplasia, type II collagen proliferation, ossification, calcium crystal deposition, and degeneration of elastic and collagen fibers. Both mechanical stress and inflammatory processes, particularly macrophage infiltration, are considered key contributors to degeneration, especially in the aging population. Yet, inflammation linked to systemic metabolic disorders-such as obesity and sarcopenia-may also significantly influence the degeneration of spinal structures. Metabolic Inflammation and the Role of Adipokines Recent research has highlighted the role of adipokines in the pathogenesis of degenerative spinal and joint diseases. Disrupted lipid metabolism and chronic low-grade inflammation contribute to tissue remodeling, extracellular matrix (ECM) degradation, and ectopic fat deposition in spinal structures. Epidural fat, normally present in the spinal canal, can become inflamed and secrete pro-inflammatory cytokines, potentially affecting adjacent tissues such as muscles and ligaments. Conditions like spinal epidural lipomatosis, which is associated with obesity, exemplify this pathological mechanism. While adipokines like leptin and visfatin have been previously associated with LF ossification and degeneration, the presence and role of others-such as adipsin, vaspin, resistin, lipocalin-2, progranulin, chemerin, omentin-1, and GDF-15-have not yet been studied in LF or epidural fat. Given their known