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

Author(s):  
Tina M. Nagel ◽  
Victor H. Barocas ◽  
David J. Nuckley

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.

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jiancheng Zheng ◽  
Jian Zhang ◽  
Xingkai Zhang ◽  
Zhiping Guo ◽  
Wenjian Wu ◽  
...  

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.


2020 ◽  
Vol 143 (2) ◽  
Author(s):  
Mitchel C. Whittal ◽  
Sara Molladavoodi ◽  
Derek P. Zwambag ◽  
Magali Millecamps ◽  
Laura S. Stone ◽  
...  

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.


Author(s):  
A. M. Ellingson ◽  
D. J. Nuckley

Chronic low back pain affects an estimated 15–65% of the U.S. population. Disc degeneration is often accredited as the origin of low back pain. With degeneration comes the breakdown of proteoglycans, loss of water content, and a decrease in the height of the intervertebral disc (IVD). These changes likely affect the disc’s viscoelastic response, making modeling and subsequent prediction of degeneration mechanics difficult. Unfortunately, much of the previous mechanical testing of IVD tissues has involved excision of the tissue and disruption of annular fibers. To gain insight into the in situ viscoelastic material properties, we have developed a new methodology of hybrid confined / in situ compression. This technique also allows for the quantification of the residual stress and strain that the IVD experiences in vivo and improved viscoelastic modeling parameters. Residual measurements, to the knowledge of the authors, have yet to be reported in previous studies. Therefore, the purpose of this study was to define the viscoelastic properties of the intact intervertebral disc as well as the residual stress/strain specific to degeneration grade and location.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Hosni Cherif ◽  
Daniel G Bisson ◽  
Matthew Mannarino ◽  
Oded Rabau ◽  
Jean A Ouellet ◽  
...  

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.


Author(s):  
Tina M. Nagel ◽  
Ramesh Raghupathy ◽  
Arin M. Ellingson ◽  
David J. Nuckley ◽  
Victor H. Barocas

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.


Author(s):  
S. Wang ◽  
W. M. Park ◽  
J. Miao ◽  
K. Wood ◽  
Y. H. Kim ◽  
...  

The most common reason for occupational low back pain is the overload on the spine [1]. Determination of the load on the spine is critical for preventing low back pain, understanding injury mechanism and developing treatment techniques and surgical implants. However, due to the limitations in technology, only few in-vivo measurements were performed using pressure transducer [1] and telemeterized implants [2]. Because of the risks involved, neither of these techniques was suitable for a large healthy population. In this study, we proposed a new non-invasive technique and estimated the forces and moments on the lumbar intervertebral discs (IVDs) of three healthy subjects during a dynamic weight lifting activity.


2021 ◽  
Vol 13 ◽  
pp. 1759720X2110280
Author(s):  
Camille Daste ◽  
Stéphanie Laclau ◽  
Margaux Boisson ◽  
François Segretin ◽  
Antoine Feydy ◽  
...  

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.


2018 ◽  
Vol 25 (6) ◽  
pp. 583-596 ◽  
Author(s):  
Michael Lukas Meier ◽  
Andrea Vrana ◽  
Petra Schweinhardt

Motor control, which relies on constant communication between motor and sensory systems, is crucial for spine posture, stability and movement. Adaptions of motor control occur in low back pain (LBP) while different motor adaption strategies exist across individuals, probably to reduce LBP and risk of injury. However, in some individuals with LBP, adapted motor control strategies might have long-term consequences, such as increased spinal loading that has been linked with degeneration of intervertebral discs and other tissues, potentially maintaining recurrent or chronic LBP. Factors contributing to motor control adaptations in LBP have been extensively studied on the motor output side, but less attention has been paid to changes in sensory input, specifically proprioception. Furthermore, motor cortex reorganization has been linked with chronic and recurrent LBP, but underlying factors are poorly understood. Here, we review current research on behavioral and neural effects of motor control adaptions in LBP. We conclude that back pain-induced disrupted or reduced proprioceptive signaling likely plays a pivotal role in driving long-term changes in the top-down control of the motor system via motor and sensory cortical reorganization. In the outlook of this review, we explore whether motor control adaptations are also important for other (musculoskeletal) pain conditions.


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