Acute mechanical injury of the human intervertebral disc: link to degeneration and pain

Alkhatib, Bashar; Dh, Rosenzweig; Krock, Emerson; Pj, Roughley; Beckman, Lorne; Steffen, Thomas; Mh, Weber; Ja, Ouellet; Haglund, Lisbet

doi:10.22203/ecm.v028a08

Cited by 96 publications

(77 citation statements)

References 60 publications

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“…Therefore, we conclude that the additional loss in cell viability in the posterolateral region with static overloading is not restricted to cell apoptosis alone, but–at least in part- also due to cell necrosis or autophagy. This is in accordance with others reports showing high inflammatory and necrotic activity with mechanical overloading and degeneration [30,53–56]. This is a particularly important finding in the light future targeted therapeutics, as it shows that implication of an agent with a broad-spectrum anti-inflammatory function is more likely to succeed, than a very specific single-target agent.…”

Section: Discussionsupporting

confidence: 91%

Static axial overloading primes lumbar caprine intervertebral discs for posterior herniation

et al. 2017

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IntroductionLumbar hernias occur mostly in the posterolateral region of IVDs and mechanical loading is an important risk factor. Studies show that dynamic and static overloading affect the nucleus and annulus of the IVD differently. We hypothesize there is also variance in the effect of overloading on the IVD’s anterior, lateral and posterior annulus, which could explain the predilection of herniations in the posterolateral region. We assessed the regional mechanical and cellular responses of lumbar caprine discs to dynamic and static overloading.Material and methodsIVDs (n = 125) were cultured in a bioreactor and subjected to simulated-physiological loading (SPL), high dynamic (HD), or high static (HS) overloading. The effect of loading was determined in five disc regions: nucleus, inner-annulus and anterior, lateral and posterior outer-annulus. IVD height loss and external pressure transfer during loading were measured, cell viability was mapped and quantified, and matrix integrity was assessed.ResultsDuring culture, overloaded IVDs lost a significant amount of height, yet the distribution of axial pressure remained unchanged. HD loading caused cell death and disruption of matrix in all IVD regions, whereas HS loading particularly affected cell viability and matrix integrity in the posterior region of the outer annulus.ConclusionAxial overloading is detrimental to the lumbar IVD. Static overloading affects the posterior annulus more strongly, while the nucleus is relatively spared. Hence, static overloading predisposes the disc for posterior herniation. These findings could have implications for working conditions, in particular of sedentary occupations, and the design of interventions aimed at prevention and treatment of early intervertebral disc degeneration.

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Section: Discussionsupporting

confidence: 91%

Static axial overloading primes lumbar caprine intervertebral discs for posterior herniation

et al. 2017

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“…Of note, PKCe is also the only peripheral mediator that was probed. There is strong evidence across a variety of pain models of different tissue injuries that spinal neuroimmune responses are correlated with pain [2,27,29,60,61,65,67,81,[87][88][89]. Importantly, similar pain pathways are initiated by WBV, suggesting potential therapeutic targets and/or helping to identify treatments for patients with these symptoms.…”

Section: Discussionmentioning

confidence: 99%

Whole-body Vibration at Thoracic Resonance Induces Sustained Pain and Widespread Cervical Neuroinflammation in the Rat

Zeeman

Kartha

Jaumard

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Whole-body vibration (WBV) is associated with back and neck pain in military personnel and civilians. However, the role of vibration frequency and the physiological mechanisms involved in pain symptoms are unknown. Questions/purposes This study asked the following questions: (1) What is the resonance frequency of the rat spine for WBV along the spinal axis, and how does frequency of WBV alter the extent of spinal compression/ extension? (2) Does a single WBV exposure at resonance induce pain that is sustained? (3) Does WBV at resonance alter the protein kinase C epsilon (PKCe) response in the dorsal root ganglia (DRG)? (4) Does WBV at resonance alter expression of calcitonin gene-related peptide (CGRP) in the spinal dorsal horn? (5) Does WBV at resonance alter the spinal neuroimmune responses that regulate pain? Methods Resonance of the rat (410 ± 34 g, n = 9) was measured by imposing WBV at frequencies from 3 to 15 Hz. Separate groups (317 ± 20 g, n = 10/treatment) underwent WBV at resonance (8 Hz) or at a nonresonant frequency (15 Hz). Behavioral sensitivity was assessed throughout to measure pain, and PKCe in the DRG was quantified as well as spinal CGRP, glial activation, and cytokine levels at Day 14. Results Accelerometer-based thoracic transmissibility peaks at 8 Hz (1.86 ± 0.19) and 9 Hz (1.95 ± 0.19, mean difference [MD] 0.290 ± 0.266, p \ 0.03), whereas the video-based thoracic transmissibility peaks at 8 Hz (1.90 ± 0.27), 9 Hz (2.07 ± 0.20), and 10 Hz (1.80 ± 0.25, MD 0.359 ± 0.284, p \ 0.01). WBV at 8 Hz produces more cervical extension (0.745 ± 0.582 mm, MD 0.242 ± 0.214, p \ 0.03) and compression (0.870 ± 0.676 mm, MD 0.326 ± 0.261, p \ 0.02) than 15 Hz (extension, 0.503 ± 0.279 mm; compression, 0.544 ± 0.400 mm). Pain is longer lasting (through Day 14) and more robust (p \ 0.01) after WBV at the resonant frequency (8 Hz) compared with 15 Hz WBV. PKCe in the nociceptors of the DRG increases according to the severity of WBV with greatest increases after 8 Hz WBV (p \ 0.03). However, spinal CGRP, cytokines, and glial activation are only evident after painful WBV at resonance. Conclusions WBV at resonance produces long-lasting pain and widespread activation of a host of nociceptive and neuroimmune responses as compared with WBV at a nonresonance condition. Based on this work, future investigations into the temporal and regional neuroimmune response to resonant WBV in both genders would be useful.

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“…Recently, injury-loaded IVDs by Alkhatib et al . (2014) [121] were able to induce acute mechanical trauma and to cause the catabolic cascade of disc degeneration. Thus, there is evidence that the CEP is of key importance to maintain a healthy disc and more investigations should be undertaken to better understand the relevance of disc injury/trauma for accelerated disc degeneration and the development of pain.…”

Section: Organ Culture and Endplate Fracture Modelmentioning

confidence: 99%

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

Gantenbein¹,

Illien-Jünger²,

Chan³

et al. 2015

CSCR

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In recent decades the application of bioreactors has revolutionized the concept of culturing tissues and organs that require mechanical loading. In intervertebral disc (IVD) research, collaborative efforts of biomedical engineering, biology and mechatronics have led to the innovation of new loading devices that can maintain viable IVD organ explants from large animals and human cadavers in precisely defined nutritional and mechanical environments over extended culture periods. Particularly in spine and IVD research, these organ culture models offer appealing alternatives, as large bipedal animal models with naturally occurring IVD degeneration and a genetic background similar to the human condition do not exist. Latest research has demonstrated important concepts including the potential of homing of mesenchymal stem cells to nutritionally or mechanically stressed IVDs, and the regenerative potential of “smart” biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we summarize the current knowledge about cell therapy, injection of cytokines and short peptides to rescue the degenerating IVD. We further stress that most bioreactor systems simplify the real in vivo conditions providing a useful proof of concept. Limitations are that certain aspects of the immune host response and pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc models are commonly used because of their availability and similarity to human IVDs. Although in vitro loading environments are not identical to the human in vivo situation, 3D ex vivo organ culture models of large animal coccygeal and human lumbar IVDs should be seen as valid alternatives for screening and feasibility testing to augment existing small animal, large animal, and human clinical trial experiments.

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Acute mechanical injury of the human intervertebral disc: link to degeneration and pain

Cited by 96 publications

References 60 publications

Static axial overloading primes lumbar caprine intervertebral discs for posterior herniation

Static axial overloading primes lumbar caprine intervertebral discs for posterior herniation

Whole-body Vibration at Thoracic Resonance Induces Sustained Pain and Widespread Cervical Neuroinflammation in the Rat

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

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