scholarly journals For whom the disc tolls: intervertebral disc degeneration, back pain and toll-like receptors

2021 ◽  
Vol 41 ◽  
pp. 355-369
Author(s):  
DG Bisson ◽  
◽  
M Mannarino ◽  
R Racine ◽  
L Haglund
Keyword(s):  
Back Pain ◽  
Intervertebral Disc ◽  
Inflammatory Cytokines ◽  
Chronic Back Pain ◽  
Proteolytic Enzymes ◽  
Treatment Modalities ◽  
Toll Like Receptors ◽  
Disc Cells ◽  
Ivd Degeneration ◽  
Pro Inflammatory Cytokines

Intervertebral disc (IVD) degeneration is characterised by catabolic and inflammatory processes that contribute largely to tissue degradation and chronic back pain. The disc cells are responsible for the pathological production of pro-inflammatory cytokines and catabolic enzymes leading to degeneration. However, this phenotypical change is poorly understood. Growing evidence in animal and human studies implicates Toll-like receptors (TLR) and their activation through danger-associated alarmins, found increasingly in degenerating IVDs. TLR signalling results in the release of pro-inflammatory cytokines and proteolytic enzymes that can directly cause IVD degeneration and back pain. This review aims to summarise the current literature on TLR activation in IVD degeneration and discuss potential treatment modalities to alleviate the inflammatory phenotype of disc cells in order to arrest IVD degeneration and back pain.

Response of Mesenchymal Stem Cells and Intervertebral Disc Cells to Inflammatory Challenge

2011 ◽  
Author(s):  
Neena Rajan ◽  
Nathaniel Stetson ◽  
Passquale Razzano ◽  
Mitchell Levine ◽  
Daniel Grande ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intervertebral Disc ◽  
Disc Disease ◽  
Clinical Model ◽  
Injury Model ◽  
Tnf Α ◽  
Disc Cells ◽  
Ivd Degeneration ◽  
Pro Inflammatory Cytokines

Human intervertebral disc (IVD) degeneration is accompanied by elevated levels of pro-inflammatory cytokines, particularly IL-1β and TNF-α [1–3]. Cytokine secretion by disc cells increases catabolic breakdown of the tissue, resulting in a positive feedback of disc integrity loss and further inflammation [4–6]. A recent study by our group has shown that severity of degeneration in an injury model can influence the therapeutic effect of cell based repair, such as treatment with mesenchymal stem cells (MSCs) [7]. The goal of this study is to measure the response of MSCs to inflammatory challenge, and to compare this response to that of differentiated disc cells from the nucleus pulposus (NP), annulus fibrosis (AF) and end plate (EP). In this study, we investigated the effects of lipopolysaccharide (LPS) on intervertebral disc cells and MSCs viability, pro-inflammatory cytokine expression and extracellular matrix (ECM) expression. LPS is an endotoxin that induces strong immune responses in animal tissue and hence widely used as a pre-clinical model of inflammation. This approach provides an opportunity to study broad aspects of the physiological inflammatory process observed in degenerative disc disease.

scholarly journals Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells

2016 ◽  
Vol 32 ◽  
pp. 123-136 ◽  
Author(s):  
BA Walter ◽  
◽  
D Purmessur ◽  
A Moon ◽  
J Occhiogrosso ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Inflammatory Cytokines ◽  
Disc Cells ◽  
Pro Inflammatory Cytokines

Experimentally Validated Computational Simulation of Lumbar Spine Intervertebral Disc Puncture

2011 ◽  
Author(s):  
Kristen E. Lipscomb ◽  
Nesrin Sarigul-Klijn
Keyword(s):  
Back Pain ◽  
Lumbar Spine ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Chronic Back Pain ◽  
Medical Condition ◽  
Computational Simulation ◽  
Element Model ◽  
Before And After ◽  
Spine Model

Back pain is a debilitating medical condition, often with an unclear source. Over time, back pain can affect the work and lifestyle of an individual by reducing job productivity and time spent on enjoyable activities. Discography of the intervertebral disc (IVD) is often used to diagnose pathology of the disc and determine if it may be a source for chronic back pain. It has recently been suggested that discography may lead to IVD degeneration, and has been a cause of controversy among spine care physicians. Using the results from a cadaveric experimental model, a finite element model was first validated. Then, a study was conducted to better understand the changes caused by discography on human spine mechanics. An anatomically accurate L3-L5 lumbar spine model was developed using computed tomography scans. Discography was simulated in the model as an area in the disc affected by needle puncture. The material properties in the nucleus pulposus were adjusted to match experimental data both before and after puncture. The results show that puncture of the IVD leads to increased deformation as well as increased stresses in the disc. Pressure in the nucleus pulposus found to decrease after puncture, and was calculated in the course of this study. Puncturing the IVD changes disc mechanics and may lead to progressive spine issues in the future such as disc degeneration. While discography has been the gold standard to determine if the disc was a source of back pain in patients for many years, the potential long-term degenerative effects of the procedure are only now coming into light, and must be closely examined.

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.

scholarly journals Synergistic Effects of Acidic pH and Pro-Inflammatory Cytokines IL-1β and TNF-α for Cell-Based Intervertebral Disc Regeneration

2020 ◽  
Vol 10 (24) ◽  
pp. 9009
Author(s):  
Chiara Borrelli ◽  
Conor T. Buckley
Keyword(s):  
Intervertebral Disc ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Cell Function ◽  
Synergistic Effects ◽  
Dominant Factor ◽  
Disc Regeneration ◽  
Tnf Α ◽  
Intervertebral Disc Regeneration ◽  
Pro Inflammatory Cytokines

The intervertebral disc (IVD) relies mainly on diffusion through the cartilaginous endplates (CEP) to regulate the nutrient and metabolites exchange, thus creating a challenging microenvironment. Degeneration of the IVD is associated with intradiscal acidification and elevated levels of pro-inflammatory cytokines. However, the synergistic impact of these microenvironmental factors for cell-based therapies remains to be elucidated. The aim of this study was to investigate the effects of low pH and physiological levels of interleukin-1ß (IL-1β) and tumour necrosis factor-α (TNF-α) on nasal chondrocytes (NCs) and subsequently compare their matrix forming capacity to nucleus pulposus (NP) cells in acidic and inflamed culture conditions. NCs and NP cells were cultured in low glucose and low oxygen at different pH conditions (pH 7.1, 6.8 and 6.5) and supplemented with physiological levels of IL-1β and TNF-α. Results showed that acidosis played a pivotal role in influencing cell viability and matrix accumulation, while inflammatory cytokine supplementation had a minor impact. This study demonstrates that intradiscal pH is a dominant factor in determining cell viability and subsequent cell function when compared to physiologically relevant inflammatory conditions. Moreover, we found that NCs allowed for improved cell viability and more effective NP-like matrix synthesis compared to NP cells, and therefore may represent an alternative and appropriate cell choice for disc regeneration.

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 Intervertebral Disc Cells Produce Interleukins Found in Patients with Back Pain

2016 ◽  
Vol 95 (6) ◽  
pp. 407-415 ◽  
Author(s):  
Yejia Zhang ◽  
Ana Chee ◽  
Peng Shi ◽  
Sherrill L. Adams ◽  
Dessislava Z. Markova ◽  
...  
Keyword(s):  
Back Pain ◽  
Intervertebral Disc ◽  
Disc Cells

scholarly journals An Update of the Systematic Appraisal of the Accuracy and Utility of Lumbar Discography in Chronic Low Back Pain

2013 ◽  
Vol 2s;16 (2s;4) ◽  
pp. SE55-SE95
Author(s):  
Laxmaiah Manchikanti
Keyword(s):  
Systematic Review ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Diagnostic Accuracy ◽  
Chronic Back Pain ◽  
Task Force ◽  
International Association ◽  
Extensive Literature ◽  
Discogenic Pain

Background: The intervertebral disc has been implicated as a major cause of chronic lumbar spinal pain based on clinical, basic science, and epidemiological research. There is, however, a lack of consensus regarding the diagnosis and treatment of intervertebral disc disorders. Based on controlled evaluations, lumbar intervertebral discs have been shown to be the source of chronic back pain without disc herniation in 26% to 39% of patients. Lumbar provocation discography, which includes disc stimulation and morphological evaluation, is often used to distinguish a painful disc from other potential sources of pain. Despite the extensive literature, intense debate continues about lumbar discography as a diagnostic tool. Study Design: A systematic review of the diagnostic accuracy of lumbar provocation and analgesic discography literature. Objective: To systematically assess and re-evaluate the diagnostic accuracy of lumbar discography. Methods: The available literature on lumbar discography was reviewed. A methodological quality assessment of included studies was performed using the Quality Appraisal of Reliability Studies (QAREL) checklist. Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were included in the analysis. However, studies scoring less than 50% are presented descriptively and critically analyzed. The level of evidence was classified as good, fair, and limited or poor based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to September 2012, and manual searches of the bibliographies of known primary and review articles. Results: Over 160 studies were considered for inclusion. Of these, 33 studies compared discography with other diagnostic tests, 30 studies assessed the diagnostic accuracy of discography, 22 studies assessed surgical outcomes for discogenic pain, and 3 studies assessed the prevalence of lumbar discogenic pain. The quality of the overall evidence supporting provocation discography based on the above studies appears to be fair. The prevalence of internal disc disruption is estimated to be 39% to 42%, whereas the prevalence of discogenic pain without assessing internal disc disruption is 26%. Conclusion: This systematic review illustrates that lumbar provocation discography performed according to the International Association for the Study of Pain (IASP) criteria may be a useful tool for evaluating chronic lumbar discogenic pain. Key words: Lumbar intervertebral disc, lumbar discography, provocation discography, analgesic discography, diagnostic accuracy

scholarly journals Immunomodulatory Responses Of Toll Like Receptors Against 2019nCoV

2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Amany Sayed Maghraby
Keyword(s):  
Inflammatory Cytokines ◽  
English Language ◽  
Toll Like Receptors ◽  
Complex Molecules ◽  
Ribonucleic Acids ◽  
Histocompatibility Complex ◽  
Tnf Α ◽  
Factor Α ◽  
Molecular Signals ◽  
Pro Inflammatory Cytokines

The present review discusses the immune signals via toll like receptors (TLRs) against 2019nCoV. We researched using different database, up to June 18th, 2020. All the included articles were published in English language. The outcome of this review, that some TLRs agonists or antagonists are progressed as drugs to combat and down regulating TLRs immune signals respectively. TLRs 3 and 4 recognized 2019nCoV spike protein through immune and molecular signals that leading to immune stimulation of pro-inflammatory cytokines and even the immune fever. While the TLRs7 and 8 recognized single-stranded ribonucleic acids (ssRNAs) leading to elevation of the tumour necrosis factor α (TNF-α), interleukin (IL)-6 and -12 levels. TLRs agonists or antagonists utilized as immunotherapeutic targets against 2019nCoV via TLRs signals. Chloroquine and hydroxychloroquine; the approval compounds for 2019nCoV therapy can be inhibiting the class II major histocompatibility complex molecules expression and antigen presentation and even immune suppressions of the pro-inflammatory cytokines profile.

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