Neck Solutions

Intervertebral disc degeneration in a primate model

Intervertebral disc degeneration in a naturally occurring primate model: radiographic and biomechanical evidence

From: J Orthop Res. 2008 Sep;26(9):1283-8

Classic degenerative disc disease is a serious health problem worldwide, whose etiological basis mechanical stimulus, biochemical changes, or natural aging is poorly understood. Animal models are critical to the study of degenerative disc disease initiation and progression and for attempts to regulate, ameliorate, or eliminate it. The macaque represents a primate model with natural disc degeneration that might serve to advance the field; we aimed to provide radiographic (morphologic) and biomechanical evidence of natural disc degeneration in this model. A factorial study design was used to examine the relationship between the radiographic appearance of disc degeneration and its biomechanical consequences. Eighteen macaques of advanced age (22.3 +/- 0.9 years) had radiographs taken to assess the degree of thoracolumbar intervertebral disc degeneration using a standard atlas method. Each spine was harvested and dynamic biomechanical tests were performed. Advancing disc degeneration (degree of disc space narrowing and osteophytosis) was associated with increased stiffness, decreased energy absorption, and increased natural frequency of the intervertebral disc. These associations linking the dynamics of the intervertebral disc and its degree of degeneration are similar to those found in humans. Our results indicate the macaque model with morphologic and biomechanical efficacy could aid in understanding the progression of disc degeneration and in developing therapeutic strategies to prevent or inhibit its course.

Association between cervical pillar hyperplasia and degenerative joint disease

Segment-specific association between cervical pillar hyperplasia and degenerative joint disease

From: Chiropractic & Osteopathy 2006, 14:21

Cervical pillar hyperplasia is a radiological finding which first made its appearance in the literature less than 30 years ago. Its etiology and clinical significance are presently unknown; nevertheless, studies have shown that cervical pillar hyperplasia is a frequently overlooked etiology for the loss of the cervical lordosis. While these findings were disputed by several authors, other consequences of cervical pillar hyperplasia are not known at the present time. It has been theorized that the architectural difference that the presence of hyperplasia introduces into the cervical pillar may cause segmental biomechanical changes and may lead to a higher prevalence of degenerative joint disease at the hyperplastic or adjacent cervical levels. The clinical significance of this phenomenon, if found to be related to degenerative joint disease, should prompt an astute clinician into evaluating the articular pillars on all cervical spine radiographs – particularly because there could be a chance that the patient may develop degeneration at the specific cervical levels and may experience associated neck pain. The architecture of the cervical pillars cannot be modified by conservative therapy; therefore, clinicians should be aware that some of the symptoms may be attributed to degeneration and may influence the expected prognosis of the management of neck pain in those particular patients.

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Magnetic Resonance Imaging for the assessment of degenerative disc disease of the lumbar spine

Advances in Magnetic Resonance Imaging for the assessment of degenerative disc disease of the lumbar spine

From: Semin Spine Surg. 2007 June; 19(2): 65–71

The intervertebral disc is characterized by a tension-resisting annulus fibrosus, and a compression-resisting nucleus pulposus composed largely of proteoglycan. Both the annulus and the nucleus function in concert to provide the disc with mechanical stability. Early disc degeneration begins in the nucleus with proteoglycan depletion. Quantitative MRI techniques have been developed to non-invasively quantify the earliest degenerative changes that occur within the disc. Our ability to identify and quantify these early biochemical changes will provide a better understanding of the pathophysiology of disc degeneration and facilitate the study of interventions that aim to halt or reverse the degenerative process.

Degenerative disc disease of the intervertebral disc is the most common cause of back-related disability among North American adults. This sometimes debilitating condition affects nearly 12 million people in the United States, and may generate direct and indirect costs exceeding 50 billion dollars annually in health-related expenditures. The radiographic evaluation of patients with degenerative disc disease often begins with plain film radiography and a standard T1- and T2-weighted MRI to assess for structural changes within the nucleus and annulus indicative of disc degeneration including a loss of T2-weighted MRI signal, loss of disc height, disc bulge or herniation, posterior element arthrosis, stenosis, and potential vertebral body compromise. While standard MRI is able to detect these later stage developments, it is not able to provide a quantitative measure of the early changes that characterize early degenerative disc disease. This limitation has led to the search for quantitative, non-invasive measures to evaluate the earliest changes involved in the initiation of the degenerative cascade. Such an imaging tool will be important for the evaluation of the patients with early degenerative disc disease, and also in the assessment of disc regenerative or restorative technologies that aim to halt or reverse the degenerative process.

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Subendplate microcirculation disturbance in intervertebral disc degeneration

Subendplate microcirculation disturbance directly contributes to intervertebral disc degeneration

From: Zhonghua Wai Ke Za Zhi. 2008 Feb 1;46(3):213-6 Article in Chinese

To build subendplate microcirculation disturbance animal model and to investigate the potential pathogenesis of intervertebral disc degeneration. Twenty four New Zealand white rabbits were divided into treatment group (Group A) and control group (Group B). In Group A, animals received endotoxin and corticosteroid application to build subendplate microcirculation disturbance animal model, validated by microthrombus staining. In Group B, animals were given no drug, but standard feeding. After 3 month, the extent of intervertebral disc degeneration was evaluated by the water content, biochemistry analysis, and morphology. Subendplate microthrombus staining confirmed the exist of microcirculation disturbance.

The water content and biochemistry components content of disc in Group A were lower than those of disc in Group B, and intervertebral disc degeneration was observed in morphology. Subendplate microcirculation disturbance can directly contribute to intervertebral disc degeneration, the nutrients diffusion barrier is the potential pathogenesis of intervertebral disc degeneration.

Caveolin-1 stress induced premature senescence in intervertebral disc degeneration

Caveolin-1 expression and stress induced premature senescence in human intervertebral disc degeneration

From: Arthritis Res Ther. 2008 Aug 5;10(4):R87 [Epub ahead of print]

Chronic and debilitating low back pain is a common condition and a huge economic burden. Many cases are attributed to age related degeneration of the intervertebral disc, however, age related degeneration appears to occur at an accelerated rate in some individuals. We have previously demonstrated biomarkers of cellular senescence within the human intervertebral disc and suggested a role for senescence in intervertebral disc degeneration. Senescence occurs with ageing, but can also occur prematurely in response to stress. We hypothesised that stress induced premature senescence occurs within the intervertebral disc and here we have investigated the expression and production of caveolin-1, a protein that has been shown previously to be upregulated in stress induced premature senescence.

Caveolin-1 gene expression in human nucleus pulposus cells was assessed by conventional and quantitative real-time PCR and caveolin-1 protein expression examined within human intervertebral discs using immunohistochemistry. Correlation between caveolin-1 and p16INK4a biomarker of cellular senescence gene expression was investigated using quantitative real-time PCR.

Caveolin-1 gene and protein expression were demonstrated within the human intervertebral disc for the first time. Nucleus pulposus cells from degenerate discs exhibited elevated levels of caveolin-1 that did not relate to increasing chronological age. A negative correlation was observed between gene expression for caveolin-1 and donor age and no correlation was found between caveolin-1 protein expression and age. A positive correlation was identified between gene expression of caveolin-1 and biomarker of cellular senescence.

Our findings are consistent with a role for caveolin-1 in degenerative rather than age induced changes in the nucleus pulposus. Its expression in intervertebral disc tissue and its association with the senescent phenotype suggests that caveolin-1 and stress induced premature senescence may play a prominent role in the pathogenesis of intervertebral disc degeneration.

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Painful disc lesion in biplanar magnetic resonance imaging and discography

Painful Disc Lesion: Can Modern Biplanar Magnetic Resonance Imaging Replace Discography?

From: J Spinal Disord Tech 2008; 21:430–435

Internal disc disruption’’ is one of the prominent somatic sources of low back pain. MRI is the most common investigation performed to evaluate discogenic pain. Though MRI has advantages of being a sensitive investigation for identifying pathologic anatomy of disc degeneration, its value is limited by its inability to evaluate the physiologic status of the disc. Studies have questioned the specificity of MRI in diagnosing discogenic pain and have reported degenerative changes in 26% to 57% of asymptomatic volunteers. Discography is a useful tool to identify the painful disc responsible for patient’s symptoms. In evaluation of discogenic low back pain there has been a debate as to whether discography should replace MRI. Proponents of discography believe that it is an invaluable tool for identifying the pathologic disc producing pain. Critics believe that discography is an invasive investigation and has no place in modern practice.

Over the last decade there has been a vast improvement in the quality of MR images. Attempts have been made to identify features on MRI scans that would correlate with patient’s symptoms and would potentially eliminate the need for discography. Such features are the vertebral end plate changes described by Modic and the high intensity zone described by Aprill and Bogduk. The implications of these findings have been a subject of controversy.

This is a prospective study aimed at correlating the results of discography with new MRI classification in a consecutive series of patients with disabling low back pain considered for spinal surgery. In addition, we also aimed to compare vertebral end plate changes and high intensity zones seen on MRI with discography findings.

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Characterization of intervertebral disc aging

Characterization of intervertebral disc aging: longitudinal analysis of a rabbit model by magnetic resonance imaging, histology, and gene expression

From: Spine. 2008 Aug 1;33(17):1821-8.

A cohort of young, healthy New Zealand White rabbits was followed longitudinally with serial magnetic resonance imaging analysis and terminal analysis of histologic changes and gene expression to examine the changes observed during normal aging in the intervertebral disc. Although there is a correlation between aging and the onset of intervertebral disc degeneration, evidence suggests that distinct pathways are involved in these processes. Our group has characterized a reproducible rabbit model of intervertebral disc degeneration by magnetic resonance imaging, radiograph, histology, and mRNA expression. However, no similar analysis has been performed longitudinally for intervertebral disc aging to allow comparison of these 2 important processes.

Four skeletally mature female NZW rabbits were housed for 122 weeks, and lumbar spine MRIs were characterized serially. Histologic and quantitative gene expression analysis of the nucleus pulposus of these aging animals was performed, and compared with adult and young rabbits. Mean magnetic resonance imaging index decreased by <25% through 120 weeks. The histologic analysis showed changes in cell composition, with abundant notochordal cells in the young, chondrocyte-like cells and notochordal cells in the adult, and clusters of hypertrophic chondrocytes in the aging discs. The PCR analysis of the nucleus pulposus showed that gene expression of collagen decreased, whereas that for proteoglycans increased with aging. BMP-2, TIMP-1, and SOX-9 expression was significantly lower in the young compared with adult discs and TGF-beta1 demonstrated lower gene expression in young and aging animals.

Although dramatic cellular changes were observed, age-related magnetic resonance imaging changes occurred in this rabbit model of normal aging at a much slower rate than in a previous injury model of degeneration. In addition, the gene expression analysis of the nucleus pulposus demonstrated remarkable differences between aging and injury induced degeneration. These results suggest that aging and injury contribute uniquely to the process of intervertebral disc degeneration.

Lumbar disc degeneration: association between osteophytes, end-plate sclerosis and disc space narrowing

Lumbar disc degeneration: association between osteophytes, end-plate sclerosis and disc space narrowing

From: Annals of the Rheumatic Diseases 2007;66:330-333

Peripheral joint osteoarthritis is characterised radiologically by the presence of osteophytes, subchondral sclerosis and joint space narrowing. Joint space narrowing is due to cartilage loss, whereas both subchondral sclerosis and osteophytes are hypertrophic responses of bone, thought to arise directly either to cartilage loss or to biomechanical stress. The pathophysiology and hence the inter-relationship of these features are however not well understood. Recently, strong associations between the presence of enthesophytes, osteophytes and bone sclerosis at various joint sites have been shown. Partly on the basis of these observations, it has been suggested that some individuals may be more likely to develop bone formation in response to disease occurrence. We looked at a series of lumbar spine radiographs and characterised the severity of the component radiographic features. Although the pathology of disc degeneration differs from peripheral joint osteoarthritis, we hypothesised that if there was a predisposition to develop new bone formation in the form of osteophyte or sclerosis in response to mechanical stress, there would be a strong association between increasing severity of the features of new bone formation. The aim of this study was to determine the strength of the association between increasing severity of osteophytes and end-plate sclerosis, and the association between both these features and disc space narrowing in the lumbar spine.

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Segmental instability in cervical spondylotic myelopathy with severe disc degeneration

Segmental instability in cervical spondylotic myelopathy with severe disc degeneration

From: Spine. 2006 May 20;31(12):1327-31

A retrospective study was conducted to investigate relationships between severe disc degeneration and segmental instability in cervical spondylotic myelopathy and to discuss surgical treatment for cervical spondylotic myelopathy with severe disc degeneration. Information on relationships between segmental instability and spinal cord compression in cervical spondylotic myelopathy with severe disc degeneration is scarce. Radiographs and magnetic resonance images of patients with cervical spondylotic myelopathy with (n = 42) and without (n = 75) severe disc degeneration were reviewed retrospectively. Cervical instability and spinal cord compression factors were analyzed. Outcomes of anterior cervical decompression and fusion and expansive laminoplasty were evaluated in medical records of follow-up clinics.

Segmental instability was found in 71.4% of patients with severe disc degeneration and 22.7% of patients without severe disc degeneration. Spinal cord compression was found at the intervertebral space of severe disc degeneration and upper adjacent disc space. The recovery rate of anterior cervical decompression and fusion and expansive laminoplasty was 60.8% and 57.1%, respectively. The upper adjacent vertebra above severe disc degeneration has inclination of segmental instability. There is static spinal cord compression in intervertebral spaces of severe disc degeneration and dynamic compression in upper adjacent intervertebral spaces. Multilevel anterior cervical decompression and fusion or expansive laminoplasty should be used for surgical treatment.

The pathogenesis of discogenic low back pain

The pathogenesis of discogenic low back pain

From: J Bone Joint Surg Br. 2005 Jan;87(1):62-7.

Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament and neuropeptides such as substance P and vasoactive-intestinal peptide in the nerve fibres. The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. Substance P, neurofilament and vasoactive-intestinal peptide immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain.