Human Annulus Fibrosus Lamellae Generate Significant Multi-Axial Forces and Moments in Biaxial Extension

2013 ◽  
Author(s):  
Tina M. Nagel ◽  
Mikhail Golman ◽  
David J. Nuckley ◽  
Victor H. Barocas
Keyword(s):  
Public Health ◽  
Low Back Pain ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Annulus Fibrosus ◽  
Public Health Issue ◽  
Low Back ◽  
Biaxial Extension ◽  
Axial Forces ◽  
Ivd Degeneration

Low back pain is a widespread public health issue affecting about 75% of Americans in their lifetime [1]. In many individuals, the origin remains unknown in spite of decades of research. However, intervertebral disc (IVD) degeneration has been theorized as a major precursor to nonspecific low back pain [2,3].

Quantification of In Vivo Deformation of Healthy Lumbar Intervertebral Discs in Flexion

2012 ◽  
Author(s):  
Tina M. Nagel ◽  
Victor H. Barocas ◽  
David J. Nuckley
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Annulus Fibrosus ◽  
Intervertebral Discs ◽  
Low Back ◽  
Ivd Degeneration ◽  
Level 2 ◽  
Walled Cylinder

Intervertebral disc (IVD) degeneration is hypothesized to be the precursor to non-specific low back pain, which is a widespread problem [1]. However, before disc degeneration can be understood, a better understanding of healthy discs must be gained. The disc is a short thick-walled cylinder with a gelatinous center, the nucleus pulposus, and a largely concentric, layered collagenous ring, the annulus fibrosus, Figure 1. The layers are referred to as lamella. The IVD is integral to the strength and flexibility of the spine. Whole disc mechanics have been widely studied, but degeneration occurs at the fiber level [2]. To understand the mechanics of degeneration, testing needs to be performed at a finer level where degenerative / injury effects occur. These effects such as tears occur in the annular lamella.

scholarly journals Reactive Oxygen Species Mediate Low Back Pain by Upregulating Substance P in Intervertebral Disc Degeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jiancheng Zheng ◽  
Jian Zhang ◽  
Xingkai Zhang ◽  
Zhiping Guo ◽  
Wenjian Wu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Low Back Pain ◽  
Back Pain ◽  
Substance P ◽  
Intervertebral Disc ◽  
Reactive Oxygen ◽  
Alternative Methods ◽  
Low Back ◽  
Oxygen Species ◽  
Ivd Degeneration

Reactive oxygen species (ROS) are thought to have a strong correlation with a number of intervertebral disc (IVD) diseases. Here, we aimed to determine whether ROS represent an etiology of low back pain (LBP) during IVD degeneration. Thirty degenerated intervertebral disc samples were obtained from patients, and ROS levels were quantified using dihydroethidium (DHE) staining. The results suggested a significant correlation between the ROS level and the severity of LBP. Subsequently, a puncture-induced LBP model was established in rats, and ROS levels significantly increased compared with those in the sham surgery group, accompanied with severe puncture-induced IVD degeneration. In addition, when ROS levels were increased by H2O2 administration or decreased by NAC treatment, the rats showed increased or decreased LBP, respectively. Based on this evidence, we further determined that stimulation with H2O2 in nucleus pulposus cells (NPCs) in vivo or in vitro resulted in upregulation of substance P (SP), a peptide thought to be involved in the synaptic transmission of pain, and that the severity of LBP decreased when SP levels were increased by exogenous SP administration or neutralized via aprepitant treatment in the IVDs of rats. In conclusion, ROS are primary inducers of LBP based on clinical and animal data, and the mechanism involves ROS stimulation of NPCs to secrete SP, which is a critical neurotransmitter peptide, to promote LBP in IVDs. Therefore, reducing the level of ROS with specific drugs and inhibiting SP may be alternative methods to treat LBP in the clinic.

Mechanical Consequence of Induced Intervertebral Disc Degeneration in the SPARC-Null Mouse

2020 ◽  
Vol 143 (2) ◽  
Author(s):  
Mitchel C. Whittal ◽  
Sara Molladavoodi ◽  
Derek P. Zwambag ◽  
Magali Millecamps ◽  
Laura S. Stone ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Mechanical Tests ◽  
Null Mouse ◽  
Low Back ◽  
Spine Mechanics ◽  
Tension And Compression ◽  
In Series ◽  
Ivd Degeneration

Abstract Intervertebral disc (IVD) degeneration is associated with low back pain (LBP) and accompanied by mechanical changes to the spine. Secreted protein acidic and rich in cysteine (SPARC) is a protein that contributes to the functioning and maintenance of the extracellular matrix. SPARC-null mice display accelerated IVD degeneration and pain-associated behaviors. This study examined if SPARC-null mice also display altered spine mechanics as compared to wild-type (WT) mice. Lumbar spines from SPARC-null (n = 36) and WT (n = 18) mice aged 14–25 months were subjected to cyclic axial tension and compression to determine neutral zone (NZ) length and stiffness. Three separate mechanical tests were completed for each spine to determine the effect of the number of IVDs tested in series (one versus two versus three IVDs). SPARC-null spine NZs were both stiffer (p < 0.001) and smaller in length (p < 0.001) than WT spines. There was an effect of the number of IVDs tested in series for NZ length but not NZ stiffness when collapsed across condition (SPARC-null and WT). Correlation analysis revealed a weak negative correlation (r = −0.24) between age and NZ length in SPARC-null mice and a weak positive correlation (r = 0.30) between age and NZ stiffness in WT mice. In conclusion, SPARC-null mice had stiffer and smaller NZs than WT mice, regardless of the number of IVDs in series being tested. The increased stiffness of these IVDs likely influences mobility at these spinal joints thereby potentially contributing to low back pain.

scholarly journals Senotherapeutic drugs for human intervertebral disc degeneration and low back pain

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Hosni Cherif ◽  
Daniel G Bisson ◽  
Matthew Mannarino ◽  
Oded Rabau ◽  
Jean A Ouellet ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Cell Cycle Progression ◽  
Ex Vivo ◽  
Low Back ◽  
Cycle Progression ◽  
Apoptosis Gene ◽  
And Function ◽  
Ivd Degeneration

Cellular senescence is a contributor to intervertebral disc (IVD) degeneration and low back pain. Here, we found that RG-7112, a potent mouse double-minute two protein inhibitor, selectively kills senescent IVD cells through apoptosis. Gene expression pathway analysis was used to compare the functional networks of genes affected by RG-7112, a pure synthetic senolytic with o-Vanillin a natural and anti-inflammatory senolytic. Both affected a functional gene network related to cell death and survival. O-Vanillin also affected networks related to cell cycle progression as well as connective tissue development and function. Both senolytics effectively decreased the senescence-associated secretory phenotype (SASP) of IVD cells. Furthermore, bioavailability and efficacy were verified ex vivo in the physiological environment of degenerating intact human discs where a single dose improved disc matrix homeostasis. Matrix improvement correlated with a reduction in senescent cells and SASP, supporting a translational potential of targeting senescent cells as a therapeutic intervention.

A Non-Linear Model to Describe the Material Properties of Single Lamellae in the Human Annulus Fibrosus

2011 ◽  
Author(s):  
Tina M. Nagel ◽  
Ramesh Raghupathy ◽  
Arin M. Ellingson ◽  
David J. Nuckley ◽  
Victor H. Barocas
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Linear Model ◽  
Material Properties ◽  
Annulus Fibrosus ◽  
Intervertebral Disc Degeneration ◽  
Low Back ◽  
Property Data ◽  
Fundamental Understanding

Roughly three out of four people experience low back pain [1]. Causes are generally unknown, but low back pain is often attributed to intervertebral disc degeneration. To understand low back pain better, much research has focused on a fundamental understanding of the disc. Physiologically analogous material properties may support improved modeling and understanding of disease progression. Unfortunately, to date, few material property data have been collected in a realistic environment.

scholarly journals Intervertebral disc therapies for non-specific chronic low back pain: a systematic review and meta-analysis

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110280
Author(s):  
Camille Daste ◽  
Stéphanie Laclau ◽  
Margaux Boisson ◽  
François Segretin ◽  
Antoine Feydy ◽  
...  
Keyword(s):  
Systematic Review ◽  
Low Back Pain ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Chronic Low Back Pain ◽  
Meta Analysis ◽  
Activity Limitations ◽  
Low Back ◽  
Short Term

Objectives: We aim to evaluate the benefits and harms of intervertebral disc therapies (IDTs) in people with non-specific chronic low back pain (NScLBP). Methods: We conducted a systematic review and meta-analysis of randomized trials of IDTs versus placebo interventions, active comparators or usual care. EMBASE, MEDLINE, CENTRAL and CINHAL databases and conference abstracts were searched from inception to June 2020. Two independent investigators extracted data. The primary outcome was LBP intensity at short term (1 week–3 months), intermediate term (3–6 months) and long term (after 6 months). Results: Of 18 eligible trials (among 1396 citations), five assessed glucocorticoids (GCs) IDTs and were included in a quantitative synthesis; 13 assessed other products including etanercept ( n = 2), tocilizumab ( n = 1), methylene blue ( n = 2), ozone ( n = 2), chymopapaine ( n = 1), glycerol ( n = 1), stem cells ( n = 1), platelet-rich plasma ( n = 1) and recombinant human growth and differentiation factor-5 ( n = 2), and were included in a narrative synthesis. Standardized mean differences (95% CI) for GC IDTs for LBP intensity and activity limitations were −1.33 (−2.34; −0.32) and −0.76 (−1.85; 0.34) at short term, −2.22 (−5.34; 0.90) and −1.60 (−3.51; 0.32) at intermediate term and −1.11 (−2.91; 0.70) and −0.63 (−1.68; 0.42) at long term, respectively. Odds ratios (95% CI) for serious and minor adverse events with GC IDTs were 1.09 (0.25; 4.65) and 0.97 (0.49; 1.91). Conclusion: GC IDTs are associated with a reduction in LBP intensity at short term in people with NScLBP. Positive effects are not sustained. IDTs have no effect on activity limitations. Our conclusions are limited by high heterogeneity and a limited methodological quality across studies. Registration PROSPERO: CRD42019106336.

scholarly journals Author response: Senotherapeutic drugs for human intervertebral disc degeneration and low back pain

2020 ◽  
Author(s):  
Hosni Cherif ◽  
Daniel G Bisson ◽  
Matthew Mannarino ◽  
Oded Rabau ◽  
Jean A Ouellet ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Author Response ◽  
Low Back

scholarly journals Ectopic expression of Smurf2 and acceleration of age-related intervertebral disc degeneration in a mouse model

2017 ◽  
Vol 27 (1) ◽  
pp. 116-126 ◽  
Author(s):  
Qiuqian Wu ◽  
Jason H. Huang
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Transgenic Mice ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Ectopic Expression ◽  
Cell Phenotype ◽  
Low Back ◽  
Age Related

OBJECTIVELumbar intervertebral disc degeneration, an age-related process, is a major cause of low-back pain. Although low-back pain is a very common clinical problem in the aging population, no effective treatment is available, largely owing to lack of understanding of the molecular mechanisms underlying disc degeneration. The goal of this study was to characterize how ectopic expression of Smurf2 driven by the collagen Type II alpha 1 (Col2a1) promoter alters disc cell phenotype and associated cellular events, matrix synthesis, and gene expression during disc degeneration in mice.METHODSTo characterize how ectopic expression of Smurf2 in Col2a1-promoter working cells affects the disc degeneration process, the authors performed histological and immunohistochemical analysis of lumbar spine specimens harvested from wild-type (WT) and Col2a1-Smurf2 transgenic mice at various ages (n ≥ 6 in each age group). To elucidate the molecular mechanism underlying Smurf2-mediated disc degeneration, the authors isolated cells from WT and Col2a1-Smurf2 transgenic lumbar intervertebral discs and performed Western blot and real-time RT-PCR (reverse transcription polymerase chain reaction) to examine the protein and mRNA levels of interesting targets.RESULTSThe authors demonstrated that approximately 30% of WT mice at 10–12 months of age had started to show disc degeneration and that the disc degeneration process was accelerated by 3–6 months in Col2a1-Smurf2 transgenic mice. Chondrocyte-like cell proliferation, maturation, and fibrotic tissue formation in the inner annulus were often accompanied by fibroblast-to-chondrocyte differentiation in the outer annulus in transgenic discs. The chondrocyte-like cells in transgenic discs expressed higher levels of connective tissue growth factor (CTGF) than were expressed in WT counterparts.CONCLUSIONSThe findings that ectopic expression of Smurf2 driven by the Col2a1 promoter accelerated disc degeneration in Col2a1-Smurf2 transgenic mice, and that higher levels of CTGF protein and mRNA were present in Col2a1-Smurf2 transgenic discs, indicate that Smurf2 accelerates disc degeneration via upregulation of CTGF.

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