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...

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Main Authors: Małgorzata Sobańska, Dawid Sobański, Rafał Staszkiewicz, Paweł Gogol, Damian Strojny, Tomasz Pawłaszek, Werner Dammerman, Beniamin Oskar Grabarek
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/5/1102
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author Małgorzata Sobańska
Dawid Sobański
Rafał Staszkiewicz
Paweł Gogol
Damian Strojny
Tomasz Pawłaszek
Werner Dammerman
Beniamin Oskar Grabarek
author_facet Małgorzata Sobańska
Dawid Sobański
Rafał Staszkiewicz
Paweł Gogol
Damian Strojny
Tomasz Pawłaszek
Werner Dammerman
Beniamin Oskar Grabarek
author_sort Małgorzata Sobańska
collection DOAJ
description <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.
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issn 2227-9059
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spelling doaj-art-1732ea694ffb41bea902616b657c3e652025-08-20T03:14:42ZengMDPI AGBiomedicines2227-90592025-05-01135110210.3390/biomedicines13051102Modulation of Neurturin Expression by Lumbosacral Spinal Stenosis, Lifestyle Factors, and Glycemic DysregulationMałgorzata Sobańska0Dawid Sobański1Rafał Staszkiewicz2Paweł Gogol3Damian Strojny4Tomasz Pawłaszek5Werner Dammerman6Beniamin Oskar Grabarek7Department of Neurosurgery, Szpital sw. Rafala in Cracow, 30-693 Cracow, PolandDepartment of Neurosurgery, Szpital sw. Rafala in Cracow, 30-693 Cracow, PolandCollegium Medicum, WSB University, 41-300 Dabrowa Gornicza, PolandCollegium Medicum, WSB University, 41-300 Dabrowa Gornicza, PolandCollegium Medicum, WSB University, 41-300 Dabrowa Gornicza, PolandCollegium Medicum, WSB University, 41-300 Dabrowa Gornicza, PolandCenter of Internal Medicine II, University Hospital Brandenburg, 03048 Brandenburg, GermanyCollegium Medicum, WSB University, 41-300 Dabrowa Gornicza, Poland<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.https://www.mdpi.com/2227-9059/13/5/1102lumbosacral spinal stenosisneurturinlifestylediabetes
spellingShingle Małgorzata Sobańska
Dawid Sobański
Rafał Staszkiewicz
Paweł Gogol
Damian Strojny
Tomasz Pawłaszek
Werner Dammerman
Beniamin Oskar Grabarek
Modulation of Neurturin Expression by Lumbosacral Spinal Stenosis, Lifestyle Factors, and Glycemic Dysregulation
Biomedicines
lumbosacral spinal stenosis
neurturin
lifestyle
diabetes
title Modulation of Neurturin Expression by Lumbosacral Spinal Stenosis, Lifestyle Factors, and Glycemic Dysregulation
title_full Modulation of Neurturin Expression by Lumbosacral Spinal Stenosis, Lifestyle Factors, and Glycemic Dysregulation
title_fullStr Modulation of Neurturin Expression by Lumbosacral Spinal Stenosis, Lifestyle Factors, and Glycemic Dysregulation
title_full_unstemmed Modulation of Neurturin Expression by Lumbosacral Spinal Stenosis, Lifestyle Factors, and Glycemic Dysregulation
title_short Modulation of Neurturin Expression by Lumbosacral Spinal Stenosis, Lifestyle Factors, and Glycemic Dysregulation
title_sort modulation of neurturin expression by lumbosacral spinal stenosis lifestyle factors and glycemic dysregulation
topic lumbosacral spinal stenosis
neurturin
lifestyle
diabetes
url https://www.mdpi.com/2227-9059/13/5/1102
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