Abstract
Degenerative lumbosacral spinal stenosis (DLSS) is a progressive condition characterized by narrowing of the spinal canal and subsequent neural compression, often leading to chronic pain and disability. Neurotrophins, particularly neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4), play essential roles in maintaining neuronal integrity and modulating nociceptive signaling; however, their involvement in DLSS and potential modulation by systemic and behavioral factors remain poorly understood. This study evaluated NT-3 and NT-4 expression in ligamentum flavum (LF) tissue from 96 patients undergoing surgical decompression for DLSS and compared the results to 85 postmortem control samples. Quantitative analyses were performed using RT-qPCR, ELISA, and immunohistochemistry. NT-3 transcript levels were markedly elevated in stenotic LF samples (fold change: 9.12 ± 0.56; p < 0.05), while NT-4 mRNA expression was significantly reduced (fold change: 0.33 ± 0.07; p < 0.05). At the protein level, both NT-3 (134 ± 5.78 pg/mL) and NT-4 (316.77 ± 8.19 pg/mL) concentrations were significantly increased compared to controls (p < 0.05). Although neurotrophin levels did not correlate directly with pain intensity or morphological severity, elevated NT-3 and NT-4 protein levels were significantly associated with obesity, diabetes, alcohol consumption, and tobacco use (p < 0.05). These findings demonstrate that NT-3 and NT-4 are differentially expressed in the ligamentum flavum of patients with DLSS and are influenced by systemic metabolic disturbances and lifestyle factors, suggesting their potential as biomarkers or therapeutic targets in degenerative spinal disease.