JOR SpinePub Date : 2025-05-27DOI: 10.1002/jsp2.70076
Karthikeyan Rajagopal, Thomas P. Schaer, Kyle D. Meadows, Madeline Boyes, Rachel Hilliard, John C. O'Donnell, George R. Dodge, Dmitriy Petrov, Dawn M. Elliott, Robert L. Mauck, Lachlan J. Smith, Neil R. Malhotra
{"title":"In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration","authors":"Karthikeyan Rajagopal, Thomas P. Schaer, Kyle D. Meadows, Madeline Boyes, Rachel Hilliard, John C. O'Donnell, George R. Dodge, Dmitriy Petrov, Dawn M. Elliott, Robert L. Mauck, Lachlan J. Smith, Neil R. Malhotra","doi":"10.1002/jsp2.70076","DOIUrl":"https://doi.org/10.1002/jsp2.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Intervertebral disc degeneration is strongly implicated as a cause of low back pain. Although the precise pathophysiological mechanisms remain elusive, perturbations in nutrition that adversely impact the cellular microenvironment of the central nucleus pulposus (NP) may be contributing factors. A comprehensive understanding of this microenvironment, including changes in nutrient availability as a function of degeneration, is critical for the development of effective cell-based treatments. The goal of this study was to adapt brain tissue oxygen probes and microdialysis catheters for in situ determination of relative NP oxygen, glucose, and lactate levels in a preclinical goat model of disc degeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Following ex vivo technical refinement in bovine caudal discs, baseline metabolite measurements were performed in vivo in the lumbar discs of 3 large frame goats. Degeneration was then induced via injection of chondroitinase ABC (ChABC) into the NP, and measurements were repeated after 12 weeks. Degeneration severity was graded using magnetic resonance imaging (MRI) and histology, and vertebral endplate porosity was assessed using microcomputed tomography.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Oxygen and lactate levels in goat NPs were significantly higher in degenerate compared to healthy discs, while glucose levels were not significantly different. ChABC-injected discs exhibited higher vertebral endplate porosity, worse histological and MRI grades, and a spectrum of cartilage endplate damage compared to healthy discs. There were significant positive correlations between MRI grade and both NP oxygen and lactate levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>We successfully adapted techniques including surgical placement, equilibration time, flow rate, and detection method for in situ measurement of oxygen, glucose, and lactate in a goat model of disc degeneration. Interestingly, while increased lactate with degeneration was expected, increased oxygen levels were unexpected. Our findings may, in part, be explained by associated alterations in disc and endplate structure, and motivate future studies to comprehensively establish the underlying mechanisms in this model.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2025-05-19DOI: 10.1002/jsp2.70077
Laura Guarnaccia, Laura Begani, Silvana Pileggi, Mauro Pluderi, Stefano Borsa, Claudia Fanizzi, Massimiliano Domenico Rizzaro, Giorgio Fiore, Laura Fontana, Rolando Campanella, Chiara Cordiglieri, Chiara Gaudino, Giovanni A. Alotta, Monica Miozzo, Emanuele Garzia, Emanuela Barilla, Lorenzo Fassina, Laura Riboni, Marco Locatelli, Giovanni Marfia, Stefania E. Navone
{"title":"In Vitro Validation of Pulsed Electromagnetic Field (PEMF) as an Effective Countermeasure Against Inflammatory-Mediated Intervertebral Disc Degeneration","authors":"Laura Guarnaccia, Laura Begani, Silvana Pileggi, Mauro Pluderi, Stefano Borsa, Claudia Fanizzi, Massimiliano Domenico Rizzaro, Giorgio Fiore, Laura Fontana, Rolando Campanella, Chiara Cordiglieri, Chiara Gaudino, Giovanni A. Alotta, Monica Miozzo, Emanuele Garzia, Emanuela Barilla, Lorenzo Fassina, Laura Riboni, Marco Locatelli, Giovanni Marfia, Stefania E. Navone","doi":"10.1002/jsp2.70077","DOIUrl":"https://doi.org/10.1002/jsp2.70077","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration (IDD) is the main contributor to chronic low back pain (LBP), the leading cause of disability worldwide, with a significant impact on the quality of life and health of common people. The etiology of IDD is still unclear, but it has been largely demonstrated the crucial role of inflammation and neuroinflammation in the pathological and degenerative cascade of events characterizing IVD degeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In this study, we evaluated the potential therapeutic effect of pulsed electromagnetic field (PEMF) on human degenerated IVD (D-IVD) cells collected from patients who underwent discectomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials & Methods</h3>\u0000 \u0000 <p>The experimental plan to test our hypothesis, involved viability assay, reactive oxide species/nitrite production, gene, and protein expression. To recapitulate the pro-inflammatory disc microenvironment occurring during IDD, interleukin-1β (IL-1β) was administered to IVD cell culture. Then, to dissect the contribution of neuroinflammatory condition to immune component, microglial cells were co-cultured with IVD-conditioned media, and viability and expression of inflammatory markers were detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our data prove that in the IVD degenerative microenvironment, the increase of pro-inflammatory mediators, extracellular matrix degradative enzymes, and neuroinflammatory markers could be reduced by PEMF therapy, resulting in an overall improvement of degenerative condition and LBP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results represent an impactful novelty for the management of people suffering from LPB, in terms of symptom relief and reduction of social-health system burden.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2025-05-19DOI: 10.1002/jsp2.70070
Timothy D. Jacobsen, S. Olga Yiantsos, Jennifer Gansau, James Meyers, Damien Laudier, James C. Iatridis
{"title":"TNFα Receptor 1 and Not Receptor 2 Affect Annulus Fibrosus and Nucleus Pulposus Response to Cytokine Challenge in a Rat Model","authors":"Timothy D. Jacobsen, S. Olga Yiantsos, Jennifer Gansau, James Meyers, Damien Laudier, James C. Iatridis","doi":"10.1002/jsp2.70070","DOIUrl":"https://doi.org/10.1002/jsp2.70070","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Painful intervertebral disc (IVD) degeneration (IVDD) involves chronic inflammation. Developing translational immunomodulatory strategies for IVDD is a priority with tumor necrosis factor alpha (TNFα) signaling an important target. TNFα binds to 2 receptors (TNFRs), with TNFR1 signaling promoting catabolism and apoptosis and TNFR2 signaling promoting anabolism and proliferation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study developed translational strategies to evaluate and modulate TNFR1 and TNFR2 signaling in rat in vivo and in vitro IVDD models. We used blocking antibodies, the TNFR2-activator Atsttrin, and small molecule inhibitors of TNFR1 to discern distinct TNFR1 and TNFR2-effects on annulus fibrosus (AF) and nucleus pulposus (NP) cells and to identify effective strategies for modulating specific TNFRs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TNFR1 was significantly increased with IVDD in vivo in the NP while TNFR2 was unaffected with very faint staining. TNFR1-specific small molecule inhibitors were effective in reducing catabolic effects of TNFα, highlighting the efficacy of this small molecule strategy for TNFR1 signaling modulation. Meanwhile, TNFR1 and TNFR2 inhibition in vitro was not effective with blocking antibodies on NP or AF cells, likely due to species-specificity of available blocking antibodies. Further, TNFR2 activation with Atsttrin was similarly ineffective, likely due to extremely low TNFR2 levels in both AF and NP cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>TNFα receptor-specific signaling is important in rat IVDD in vivo and in vitro. TNFR1 inhibition was more effective with small molecules than using blocking antibodies. Low levels of TNFR2 in rat AF and NP cells and lack of efficacy of TNFR2-activator Atsttrin suggest native AF and NP cells have little capacity for TNFR2-dependent IVD repair.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2025-05-15DOI: 10.1002/jsp2.70073
David J. Lillyman, Evie C. Reddick, Kayla E. Ney, Sydney M. Caparaso, Rebecca A. Wachs
{"title":"An Extracellular Matrix Hydrogel Restores Disc Volume and Alleviates Axial Hypersensitivity in a Rat Model of Disc-Associated Pain","authors":"David J. Lillyman, Evie C. Reddick, Kayla E. Ney, Sydney M. Caparaso, Rebecca A. Wachs","doi":"10.1002/jsp2.70073","DOIUrl":"https://doi.org/10.1002/jsp2.70073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic low back pain is a global socioeconomic crisis, and the majority of those treated for this condition fail to reach long-term remission. Intervertebral disc degeneration is the predominant associative factor in chronic low back pain. Degenerated discs present with mechanical instability, inflammation, and nerve sprouting. Patients treated with spinal stabilizing procedures often report pain alleviation indicating aberrant spinal mechanics, could be causative in the production of pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>With this knowledge, a therapeutic was engineered from decellularized healthy porcine nucleus pulposus tissue mixed with type I collagen and a chemical crosslinker, genipin, to treat mechanical instability and pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vitro, this hydrogel, termed dNP+, was spontaneously fibrillogenic at 37°C and cytocompatible with primary human disc cells and exhibited the capacity to improve the intervertebral disc storage modulus after injury. In vivo, in a rat model of discogenic low back pain, dNP+ proved effective at restoring degenerated disc volume, decreasing axial hypersensitivity, and decreasing spontaneous pain-like behavior when administered 9 weeks after disc degeneration was initiated. However, dNP+ did not alter nerve presence or restore disc morphology when compared to injured discs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Conclusion: Altogether, the data collected in this study concluded that dNP+ was an effective treatment for pain-like behavior in a robust animal model of chronic disc-associated low back pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2025-05-15DOI: 10.1002/jsp2.70072
Jeffrey L. Hutchinson, Amalie J. Hutchinson, Joy Feng, Cheryle A. Séguin
{"title":"The Role of Sex Hormones in Cartilaginous Tissues: A Scoping Review","authors":"Jeffrey L. Hutchinson, Amalie J. Hutchinson, Joy Feng, Cheryle A. Séguin","doi":"10.1002/jsp2.70072","DOIUrl":"https://doi.org/10.1002/jsp2.70072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The use of sex hormones in the clinic for the management of musculoskeletal conditions is increasingly common. Despite this, the role of sex hormones in various joint tissues such as the intervertebral disc (IVD), temporomandibular joint (TMJ), and articular cartilage remains poorly understood. Here, we employ a database search strategy to critically examine the available literature in this field through a scoping review.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using a 4-step protocol, primary research articles pertaining to sex hormones and the IVD, TMJ, or articular cartilage were identified and reviewed by two independent reviewers. ~3900 articles were identified in our initial search, and after review, ~140 were identified to be relevant to our tissues of interest and the effects of sex hormones.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Within all joint tissues investigated here, there were limited investigations on the effects of testosterone. Studies reported here for these tissues indicate that sex hormones are likely beneficial in the context of age-associated joint diseases, but there are important limitations to how this translates to the clinic given that various animal models can display distinct responses to sex hormone exposure. Direct comparisons of sex hormone therapies are limited between biological sexes, but evidence indicates that the molecular responses are likely similar. Current evidence indicates that sex hormone exposure likely has anti-inflammatory effects within joint tissues at the level of gene and protein expression, but the mechanism is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Sex hormones such as testosterone and estrogen play an important role in inflammatory signaling within joint tissues, which could lead to novel interventions within the clinic for joint degeneration. However, understanding the biological mechanisms of hormones in these distinct tissues, between sexes, and with age is imperative for their proper implementation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2025-05-15DOI: 10.1002/jsp2.70071
Sabina M. Pinto, Jason P. Y. Cheung, Dino Samartzis, Jaro Karppinen, Yong-Ping Zheng, Marco Y. C. Pang, Maryse Fortin, Arnold Y. L. Wong
{"title":"Relationship Between Lumbar Multifidus Morphometry and Pain/Disability in Individuals With Chronic Nonspecific Low Back Pain After Considering Demographics, Fear-Avoidance Beliefs, Insomnia, and Spinal Degenerative Changes","authors":"Sabina M. Pinto, Jason P. Y. Cheung, Dino Samartzis, Jaro Karppinen, Yong-Ping Zheng, Marco Y. C. Pang, Maryse Fortin, Arnold Y. L. Wong","doi":"10.1002/jsp2.70071","DOIUrl":"https://doi.org/10.1002/jsp2.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although individuals with chronic low back pain (CLBP) show increased fatty infiltration in the lumbar multifidus muscle (LMM), it remains unclear whether LMM changes are related to clinical outcomes (such as pain and disability) after considering confounders (spinal phenotypes, fear-avoidance beliefs [FABs] and insomnia). This study examined: (1) differences in confounders and LMM characteristics between individuals with and without CLBP; and (2) associations between confounders, LMM parameters, and clinical outcomes in the CLBP group alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants (CLBP = 70 and asymptomatic people = 67) underwent lumbar magnetic resonance imaging. Outcome measures comprised the numeric pain rating scale, the Roland–Morris Disability Questionnaire, the Fear-Avoidance Beliefs Questionnaire (FABQ), and the Insomnia Severity Index (ISI) Scale. LMM morphometry at L3-S1 (cross-sectional area, total volume, and fatty infiltration) was measured using a customized MATLAB program. Spinal phenotypes (disc degeneration, high-intensity zones, Modic changes [MCs], Schmorl's nodes, facet joint degeneration [FJD], and facet tropism [FT]) were scored. The between-group differences were analyzed using linear mixed models and chi-squared/Fisher's exact tests. Univariate and multivariate analyses evaluated associations between clinical outcomes and other outcome measures in the CLBP group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The CLBP group demonstrated more severe disc degeneration and FJD at all levels, and greater FT at L5/S1 than asymptomatic participants (<i>p</i> < 0.05). The average LMM total volume at L3/4 and the percentage of fatty infiltration in LMM in the L3-S1 region were greater in the CLBP group than in asymptomatic counterparts (<i>p</i> < 0.05). The presence of MC at L4 and FJD at L4/5 and L4-S1 was significantly related to pain intensity in the CLBP group. Similarly, FABQ-Work and ISI scores were significantly related to pain intensity (explaining 37% of the variance in pain).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The CLBP group displays more fatty infiltration in the LMM, but their LMM morphometric parameters are unrelated to pain/disability after considering spinal phenotypes, FABs, and insomnia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2025-05-15DOI: 10.1002/jsp2.70074
{"title":"Correction to “Gut Microbiome and Metabolome Changes in Chronic Low Back Pain Patients With Vertebral Bone Marrow Lesions”","authors":"","doi":"10.1002/jsp2.70074","DOIUrl":"https://doi.org/10.1002/jsp2.70074","url":null,"abstract":"<p>W. Li, J. Tu, J. Zheng, et al., Gut Microbiome and Metabolome Changes in Chronic Low Back Pain Patients With Vertebral Bone Marrow Lesions. <i>JOR Spine</i> 8 (2025): e70042, https://doi.org/10.1002/jsp2.70042</p><p>In the article cited above, Affiliations 8 and 9 were mistakenly merged. This has now been corrected, and 16 author affiliations are now shown.</p><p>We apologize for this error.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2025-05-14DOI: 10.1002/jsp2.70069
William Anderst, C. James Kim, Kevin M. Bell, Tom Gale, Cate Gray, Carol M. Greco, Clarissa LeVasseur, Gina McKernan, Sabreen Megherhi, Charity G. Patterson, Sara R. Piva, Caroline Pellegrini, Michael J. Schneider, Joseph Shoemaker, Patrick Smith, Nam V. Vo, Gwendolyn A. Sowa
{"title":"Intervertebral Lumbar Spine Kinematics in Chronic Low Back Pain Patients Measured Using Biplane Radiography","authors":"William Anderst, C. James Kim, Kevin M. Bell, Tom Gale, Cate Gray, Carol M. Greco, Clarissa LeVasseur, Gina McKernan, Sabreen Megherhi, Charity G. Patterson, Sara R. Piva, Caroline Pellegrini, Michael J. Schneider, Joseph Shoemaker, Patrick Smith, Nam V. Vo, Gwendolyn A. Sowa","doi":"10.1002/jsp2.70069","DOIUrl":"https://doi.org/10.1002/jsp2.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic low back pain (cLBP) presents as a heterogeneous condition, making diagnosis and treatment challenging. Lumbar spine intervertebral kinematics may provide an objective assessment of patients with cLBP that may be used to inform treatment decisions and evaluate the efficacy of interventions. The purpose of this study was to provide a quantitative description of intervertebral motion in the lumbar spine during flexion/extension (F/E) and lateral bending (LB) in individuals with cLBP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from 125 individuals is included in this analysis (M: 53; F: 72; <i>n</i> = 66 < 60 years of age; average BMI: 25.7 ± 3.6 kg/m<sup>2</sup>). Dynamic biplane radiography (DBR) and a validated volumetric model-based tracking system were used to assess intervertebral motion at every lumbar level (L1-L2 through L5-S1) during active F/E and LB movements in individuals with cLBP. The outcome measures were the intervertebral translation and rotation range of motion (ROM), the contribution of each motion segment to lumbar motion, the anterior–posterior slip per degree of flexion (SPDF), and trial-to-trial repeatability as assessed by the standard deviation in continuous kinematics waveforms over 3 trials of each movement. Outcomes were calculated for the entire group as well as for the subgroups of men, women, individuals less than 60 years of age, and individuals 60 or more years of age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean intervertebral F/E ROM progressively increased from 6.8° ± 3.1° at the L1-L2 through the L4-L5 motion segments, then decreased from 9.7° ± 5.2° at L4-L5 to 8.4° ± 4.9° at L5-S1. However, substantial variability among individuals was observed, and only 7 participants (5.6%) followed this ROM pattern. The mean intervertebral LB ROM increased from 8.8° ± 3.2° at L1-L2 to 9.1° ± 4.2° at L2-L3 and then progressively decreased from the L2-L3 through the L5-S1 motion segments to 2.7° ± 1.8°. However, only 13 participants (10.4%) followed this ROM pattern. On average, the L1-L2, L2-L3, and L5-S1 motion segments were the main contributors to F/E when the torso was near the upright neutral position. L2-L3, L3-L4, and L4-L5 were the main contributors to midrange flexion and extension, and L3-L4, L4-L5, and L5-S1 were the main contributors to lumbar motion when the trunk was near full flexion. L1-L2 and L2-L3 were the main contributors to lumbar LB near the neutral position and through the midrange. The contributions from L4-L5 and L5-S1 peaked at the neutral position and at maximum bending. SPDF was similar in the L1-L2, L2-L3, and L3-L4 motion segmen","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms and Therapeutic Strategies of Macrophage Polarization in Intervertebral Disc Degeneration","authors":"Kaiyuan Zheng, Siyu Wang, Meng Deng, Yaomin Luo, Wen Li, Lianlin Zeng, Yinxu Wang","doi":"10.1002/jsp2.70065","DOIUrl":"https://doi.org/10.1002/jsp2.70065","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP), contributing significantly to global disability and productivity loss. Its pathogenesis involves complex processes, including inflammation, cellular senescence, angiogenesis, fibrosis, neural ingrowth, and sensitization. Emerging evidence highlights macrophages as central immune regulators infiltrating degenerated discs, with macrophage polarization implicated in IVDD progression. However, the mechanisms linking macrophage polarization to IVDD pathology remain poorly elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature review was conducted by searching major databases (PubMed, Web of Science, and Scopus) for studies published in the last decade (2014–2024). Keywords included “intervertebral disc degeneration,” “macrophage polarization,” “inflammation,” “senescence,” and “therapeutic strategies.” Relevant articles were selected, analyzed, and synthesized to evaluate the role of macrophage polarization in IVDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Macrophage polarization dynamically influences IVDD through multiple pathways. Pro-inflammatory M1 macrophages exacerbate disc degeneration by amplifying inflammatory cytokines (e.g., TNF-α, IL-1β), promoting cellular senescence, and stimulating abnormal angiogenesis and neural ingrowth. In contrast, anti-inflammatory M2 macrophages may mitigate degeneration by suppressing inflammation and enhancing tissue repair. Therapeutic strategies targeting macrophage polarization include pharmacological agents (e.g., cytokines, small-molecule inhibitors), biologic therapies, gene editing, and physical interventions. Challenges persist, such as incomplete understanding of polarization triggers, lack of targeted delivery systems, and limited translational success in preclinical models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Macrophage polarization is a pivotal regulator of IVDD pathology, offering promising therapeutic targets. Future research should focus on elucidating polarization mechanisms, optimizing spatiotemporal control of macrophage phenotypes, and developing personalized therapies. Addressing these challenges may advance innovative strategies to halt or reverse IVDD progression, ultimately improving clinical outcomes for LBP patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JOR SpinePub Date : 2025-05-14DOI: 10.1002/jsp2.70067
Manmeet S. Dhiman, Mohammed A. Salaam, Taylor J. Bader, Fred Nicholls, W. Bradley Jacobs, Kenneth C. Thomas, Jacques Bouchard, Paul T. Salo, David A. Hart, Ganesh Swamy, Neil A. Duncan
{"title":"Human Disc Degeneration Is Accompanied by a Loss of Anterior Annulus Fibrosus Interlamellar Matrix Integrity as Assessed by Peel Tests","authors":"Manmeet S. Dhiman, Mohammed A. Salaam, Taylor J. Bader, Fred Nicholls, W. Bradley Jacobs, Kenneth C. Thomas, Jacques Bouchard, Paul T. Salo, David A. Hart, Ganesh Swamy, Neil A. Duncan","doi":"10.1002/jsp2.70067","DOIUrl":"https://doi.org/10.1002/jsp2.70067","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Disc degeneration (DD) is accompanied by biomechanical changes in the intervertebral discs. The lamellae of the annulus fibrosus (AF) are interconnected through the interlamellar matrix (ILM). The ILM contains interlamellar cross-bridges, connecting the lamellae radially in three dimensions. Weakening of the ILM and the cross-bridges could contribute to delamination between the lamellae, reducing their ability to resist loads and thus contributing to loss of AF integrity associated with the development and progression of degeneration. The objective of the present study was to quantify the differences in interlamellar mechanical properties of fresh AF samples from surgical DD individuals compared to AF samples from non-DD donors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An interlamellar peel test was performed on fresh AF tissue collected from DD surgeries (<i>n</i> = 36) and non-DD organ donors (<i>n</i> = 13). The tissue was peeled at 0.5 mm/s until complete separation. Interlamellar mechanical properties were calculated from the force-displacement curve.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Samples from DD individuals had lower Peel Stiffness (<i>p</i> = 0.001), Peel Strength (<i>p</i> = 0.001), Peel Toughness (<i>p</i> = 0.0009), and Standard Deviation of the Peel Stress (<i>p</i> = 0.02) compared to the tissue from non-DD organ donors. Age had moderate negative correlations with Peel Stiffness (<i>R</i> = −0.59), Peel Strength (<i>R</i> = −0.66), and Peel Toughness (<i>R</i> = −0.69) for non-DD samples only.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The mechanical integrity of the ILM was determined to be lower in surgical DD individuals compared to non-DD donors. Aging alone may not have affected the results, and rather, loss of the integrity of ILM during disease progression appeared to have significantly contributed to the differences observed. This study provides new mechanical insights into the delamination often observed in the AF of surgical DD individuals. Future biochemical and immunolocalization studies, integrated with mechanical data, will aim to understand the role of collagen and elastin structure and composition in the decreased mechanical integrity of affected tissues.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}