Modulation of Neurturin Expression by Lumbosacral Spinal Stenosis, Lifestyle Factors, and Glycemic Dysregulation

<b>Background/Objectives</b>: Lumbosacral spinal stenosis (LSS) is a degenerative condition characterized by narrowing of the spinal canal and associated neuropathic pain. While mechanical compression is well-characterized, the molecular mechanisms contributing to symptom severity remain poorly understood. Neurturin (NRTN), a member of the glial cell line-derived neurotrophic factor family, has emerged as a potential mediator of neural plasticity and nociception, but its role in spinal stenosis is largely unexplored. <b>Methods</b>: We analyzed <i>NRTN</i> mRNA and protein expression in ligamentum flavum samples from 96 patients undergoing surgery for LSS and 85 non-degenerative postmortem controls. Quantification was performed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. Pain severity Visual Analog Scale (VAS), body mass index (BMI), diabetes, smoking, and alcohol use were assessed as modulators of NRTN expression. <b>Results</b>: NRTN expression was significantly elevated in LSS patients versus controls at both transcript and protein levels (<i>p</i> < 0.05). NRTN levels positively correlated with pain intensity (VAS; ANOVA <i>p</i> = 0.032 for mRNA, <i>p</i> = 0.041 for protein). Multivariate regression identified BMI (β = 0.50, <i>p</i> = 0.015) and diabetes (β = 0.39, <i>p</i> = 0.017) as independent predictors of increased NRTN expression. Alcohol use also showed a positive association (<i>p</i> = 0.046), while smoking showed no significant independent effect. <b>Conclusions</b>: Neurturin is upregulated in ligamentum flavum tissue from LSS patients and correlates with pain severity and metabolic risk factors. These findings suggest NRTN as a potential biomarker and therapeutic target in degenerative spine disease. Further longitudinal and mechanistic studies are warranted to elucidate its role in chronic pain and neuroinflammation.