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PubMed1980

Auto-immunity and intervertebral disc disease.

The immunological approach to intervertebral disc disease is based on a number of clinical and biological facts observed in human pathology. Even allowing for the fact that the number of cases reported in recent research is small, and that the methods of clinical and biological investigation have not been standardised, and that there are differences of opinion concerning the nature of the disc antigen, encouraging results have nonetheless been reached in support of the immunity hypothesis. The importance of the immunity phenomenon in the multifactorial pathogenesis of disc disease still remains open to discussion. In the present paper the immunological data recently acquired on disc disease is reviewed.

Adult↗
PubMed1998

Matrix metalloproteinases: the clue to intervertebral disc degeneration?

STUDY DESIGN: A review of the current literature on the role of matrix metalloproteinases in intervertebral disc degeneration. OBJECTIVE: To detail the characteristics of matrix metalloproteinases (classification, structure, substrate specificity and regulation) and to report previous studies of intervertebral discs. SUMMARY OF BACKGROUND DATA: Degeneration of the intervertebral disc, a probable prerequisite to disc herniation, is a complex phenomenon, and its physiopathologic course remains unclear. Matrix metalloproteinases probably play an important role but have received sparse attention in the literature. METHODS: A systematic review of studies reporting a role of matrix metalloproteinases in intervertebral disc degeneration. RESULTS: In several studies, investigators have reported the presence of proteolytic enzymes from disc culture systems and disc tissue extracts in degenerated human intervertebral discs, especially collagenase-1 (MMP-1) and stromelysin-1 (MMP-3). The matrix metalloproteinases are regulated by specific inhibitors (tissue inhibitors of metalloproteinases, or TIMPS), cytokines (interleukin-1), and growth factors. CONCLUSIONS: This field of application is of particular interest because conventional treatments are disappointing in chronic low back pain. Clinical trials with specific inhibitors of metalloproteinases are beginning in osteoarthritis.

Extracellular Matrix↗
PubMed2002

New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration.

STUDY DESIGN: A new rabbit model was developed that produces disc degeneration through the application of controlled and quantified axial mechanical load. OBJECTIVES: To characterize the changes associated with disc degeneration, and to evaluate the feasibility of local transfer of agents to the compressed discs to stimulate disc regeneration. SUMMARY OF BACKGROUND DATA: Studies have shown that accelerated degeneration of the intervertebral disc results from altered mechanical loading conditions. The development of methods for the prevention of disc degeneration and the restoration of disc tissue that has already degenerated is needed. METHODS: New Zealand white rabbits (n = 33) were used for this study. The discs in five animals remained unloaded and served as controls, whereas in 28 animals the discs were axially compressed using a custom-made external loading device. After 1 (n = 7), 14 (n = 7), and 28 (n = 7) days of dynamic loading, or 28 (n = 7) days of loading followed by 28 days of unloaded recovery time, the animals were killed and the lumbar spine was harvested for tissue preparation. Disc height, disc morphology, cell viability, disc stiffness, and load to failure were measured. Recombinant adenovirus encoding for two different marker genes (Ad-Luciferase and Ad-LacZ) was injected into the discs in loaded specimens and the gene expression was measured. RESULTS: The unloaded intervertebral discs of the rabbits consisted of a layered anulus fibrosus, a cartilaginous endplate, and a nucleus pulposus comparable with those of humans. After 14 and 28 days of loading, the discs demonstrated a significant decrease in disc space. Histologically, disorganization of the architecture of the anulus occurred. The number of dead cells increased significantly in the anulus and cartilage endplate. These changes were not reversible after 28 days of unloading. The stiffness and the load to failure did not change significantly in the discs after 28 days of loading, as compared with the unloaded control discs. Adenovirus-mediated gene transfer to discs was tolerated by all the animals. LacZ gene expression was found 2 weeks after injection of AdLacZ in loaded disc cells. CONCLUSIONS: The results of this study suggest that disc degeneration can be induced by axial dynamic loading in the rabbit intervertebral disc. The compressed rabbit intervertebral discs were large enough for the application of local transmitters through a percutaneous approach. We anticipate that this animal model could be used as a basic model to study intervertebral disc degeneration and to investigate new local therapeutic strategies for maintaining disc health or initiating tissue repair.

Adenoviridae↗
PubMed1999

The effect of hydrostatic pressure on intervertebral disc metabolism.

STUDY DESIGN: By the use of pressure vessels, hydrostatic pressure was applied to intervertebral disc cells cultured in an alginate. OBJECTIVE: To test the hypothesis that hydrostatic pressure directly affects the synthesis of collagen and proteoglycan by the intervertebral disc cells. SUMMARY OF BACKGROUND DATA: The influence of compression (both hydrostatic and mechanical) on chondrocyte metabolism was examined in a number of earlier studies. However, in most of these studies, articular cartilage, not intervertebral disc, was used, and in none of these was hydrostatic pressure applied to intervertebral disc cells cultured in alginate. METHODS: Fresh cells were harvested from the lumbar intervertebral discs of dogs. Before their suspension in an alginate gel system, the cells were plated and expanded until they reached confluence. Then, by use of the alginate gel system, the cells were exposed (for up to 9 days) to specific values of hydrostatic pressure inside two stainless steel pressure vessels. One vessel was kept at 1 MPa and the other at atmospheric pressure. The effects of 1 MPa were compared against atmospheric pressure by measuring the incorporation of [3H]-proline and [35S]-sulfate into collagen and proteoglycans, respectively, for the anulus cells and nucleus cells separately, and by determining whether this incorporation was reflected by changes in the levels of mRNA for aggrecan and Types I and II collagen. RESULTS: Comparisons with atmospheric pressure yielded the following findings: 1) In the incorporation studies, the nucleus and anulus cells exhibited a differential response to a hydrostatic pressure of 1 MPa. Collagen and proteoglycan syntheses were stimulated in the nucleus cells and inhibited in the anulus cells. 2) There was no significant increase in cell proliferation, as measured by DNA content, at 1 MPa for either the anulus or nucleus cells. 3) The mRNA levels of collagen (Col 1A1 and Col 2A1) and aggrecan increased at 1 MPa in both the nucleus and anulus cells. CONCLUSIONS: Hydrostatic pressure directly affects the synthesis of collagen and proteoglycan by the intervertebral disc cells.

Aggrecans↗
PubMed2002

Improving the fixation of an artificial intervertebral disc.

The fixation of an artificial intervertebral disc has been studied especially with respect to the dimensions, the convexity of the endplates and the size of the fixation elements. From literature and cadaveric vertebrae, the dimensions and shape of the lumbar vertebral endplates were determined and the dimensions of fixation ribs for the artificial intervertebral disc were calculated. To withstand shear forces and prevent dislocation, two sagittal ribs, each 3.5 mm in height and at least 20 mm in length and four transversal ribs, each 1.5 mm in height and with a total length of 60 mm are sufficient. A range of five different sagittal diameters was selected as sufficient for all patients. At least 72.6 % of the endplate of the vertebrae is covered. A convexity with a radius of 140 mm limits the gap to 0.62 mm.

Biomechanical Phenomena↗
PubMed1999

Strain on intervertebral discs after anterior cervical decompression and fusion.

STUDY DESIGN: An analysis of the change in strain distribution of intervertebral discs present after anterior cervical decompression and fusion by an original method. The analytical results were compared to occurrence of herniation of the intervertebral disc on magnetic resonance imaging. OBJECTIVES: To elucidate the influence of anterior cervical decompression and fusion on the unfused segments of the spine. SUMMARY OF BACKGROUND DATA: There is no consensus regarding the exact significance of the biomechanical change in the unfused segment present after surgery. METHODS: Ninety-six patients subjected to anterior cervical decompression and fusion for herniation of intervertebral discs were examined. Shear strain and longitudinal strain of intervertebral discs were analyzed on pre- and postoperative lateral dynamic routine radiography of the cervical spine. Thirty of the 96 patients were examined by magnetic resonance imaging before and after surgery, and the relation between alteration in strains and postsurgical occurrence of disc herniation was examined. RESULTS: In the cases of double- or triple-level fusion, shear strain of adjacent segments had increased 20% on average 1 year after surgery. Thirteen intervertebral discs that had an abnormally high degree of strain showed an increase in longitudinal strain after surgery. Eleven (85%) of the 13 discs that showed an abnormal increase in longitudinal strain had herniation in the same intervertebral discs with compression of the spinal cord during the follow-up period. Relief of symptoms was significantly poor in the patients with recent herniation. CONCLUSIONS: Close attention should be paid to long-term biomechanical changes in the unfused segment.

Adult↗
PubMed1996

Human group II phospholipase A2 in normal and diseased intervertebral discs.

We measured calcium-dependent phospholipase A2 (PLA2) activity and immunoreactive group II PLA2 levels of 54 normal discs obtained from cadavers and 73 disc samples surgically obtained from patients with spinal disorders, including intervertebral disc herniations, spondylosis, and spondylolisthesis. Both cadaveric and surgical disc specimens contained about two-fold greater PLA2 activity than the ileal mucosa, one of the richest sources of group II PLA2. Discs of middle-aged cases had significantly higher activity than those of younger and elder cases. In cadaveric normal discs, calcium-dependent PLA2 activity was significantly higher in females than in males. Annulus fibrosus and nucleus pulposus contained the same PLA2 levels. In diseased disc, herniated fragments that had extruded or protruded out of the discs possessed lower activity than other parts of discs in the intervertebral space. Immunoreactive group II PLA2 levels of intervertebral discs closely correlated with PLA2 enzymatic activity. We purified a PLA2 from human intervertebral disc to homogeneity to further identify the isozymic nature of discal PLA2. Its NH2-terminal amino acid sequences and molecular weight were identical to those of human group II PLA2. Immunohistochemical analysis using a monoclonal anti-group II PLA2 antibody showed that in both annulus fibrosus and nucleus pulposus chondrocytes contained intense group II PLA2 immunoreactivity in their cytoplasm, and that the matrix contained no substantial immunoreactivity. These results suggest that group II PLA2 in chondrocytes has important physiological roles in discal ordinary metabolism, maintaining discal homeostasis.

Adolescent↗
PubMed2004

A diffusion and T2 relaxation MRI study of the ovine lumbar intervertebral disc under compression in vitro.

The ovine lumbar intervertebral disc is a useful model for the human lumbar disc. We present preliminary estimates of diffusion coefficients and T2 relaxation times in a pilot MRI study of the ovine lumbar intervertebral disc during uniaxial compression in vitro, and identify factors that hamper the ability to accurately monitor the temporal evolution of the effective diffusion tensor at high spatial resolution.

Animals↗
PubMed2003

Cyclic tensile stretch modulates proteoglycan production by intervertebral disc annulus fibrosus cells through production of nitrite oxide.

Degeneration of the intervertebral disc is the main pathophysiological process implicated in low back pain and is a prerequisite to disc herniation. Clinically, mechanical forces are important modulators of the degeneration, but the underlying molecular mechanism is not known and needs investigation to identify the biological target. The aim of this work was to study, at the molecular level, the effects of cyclic tensile stretch (CTS) on the production of proteoglycan by intervertebral disc annulus fibrosus cells since proteoglycans seem to be implicated in the dynamic process of intervertebral disc degeneration. Such cells of rabbit were cultured at high density on plates with a flexible bottom. CTS was applied with use of a pressure-operated instrument to deform the plates. With CTS at 1% elongation (1 Hz frequency), the level of (35)S-labeled neosynthesized proteoglycans that accumulated in the cellular pool or were secreted in the culture medium did not change, but at 5% elongation, the level was significantly reduced after 8 h of stimulation (30 and 21%, respectively) and further reduced at 24 h (43 and 41%, respectively). Introducing the protein synthesis inhibitor cycloheximide had no effect on this result. Neither aggrecan and biglycan expression nor proteoglycan physical properties were modified. The level of nitrite oxide production significantly increased by 3.5 times after 8 h of 5% elongation. Introducing the nitric oxide synthase (NOS) inhibitors N(G)-methyl-l-arginine or N-omega nitro-l-arginine diminished the effects of CTS on the production of nitrite oxide and proteoglycans. By contrast, introducing N-iminoethyl-l-lysine (a more specific inhibitor of inductible NOS [iNOS]) had little or no effect. Taken together, these results suggest that cNOS activation seems to be more implicated in the 5% CTS modulation of proteoglycan production than iNOS activation. These results suggest that CTS can help regulate the intervertebral disc matrix by decreasing proteoglycan production through a post-translational regulation involving nitrite oxide. This result could be of interest in the development of local therapeutic strategies aimed at controlling intervertebral disc degeneration.

Animals↗
PubMed1997

Treatment of canine intervertebral disc displacement with chondroitinase ABC.

STUDY DESIGN: This study demonstrated the therapeutic value of chemonucleolysis with chondroitinase ABC to canine intervertebral disc displacement. OBJECTIVES: To determine the efficacy of Chondroitinase ABC in the management of canine intervertebral disc displacement. SUMMARY OF BACKGROUND DATA: No previous study has assessed the chemonucleolysis with chondroitinase ABC in the displaced discs. The changes of intervertebral disc syndrome were evaluated in this study. METHODS: Fifty-nine dogs with symptoms and signs of intervertebral disc displacement were treated with Chondroitinase ABC by a single intradisc injection. The changes in symptoms and signs of disc herniation in the dogs were followed from 7 days to 3 years after treatment. RESULTS: Forty-eight dogs were evaluated for the efficacy of the chemonucleolytic treatment with chondroitinase ABC. At 1 week after injection, 45 of 48 dogs showed some improvement in symptoms and signs. No adverse reactions were observed. There was no recurrence of symptoms in nine dogs who were observed from 14 months to 3 years after injection. CONCLUSION: Chemonucleolytic treatment with chondroitinase ABC is an effective and safe method for the management of canine intervertebral disc displacement.

Animals↗
PubMed1992

Changes seen on magnetic resonance imaging in the intervertebral disc space after chemonucleolysis: a hypothesis concerning regeneration of the disc after chemonucleolysis.

Measurements of the intervertebral disc space were made by magnetic resonance imaging and plain film examinations over a period of 2 years in 26 patients who had undergone chemonucleolysis. The height of the posterior portion of the disc decreased after 3 months and never recovered; the height of the anterior portion also decreased but recovered slightly over the same period. The angle of lordosis and the range of motion in the treated segment were decreased, but recovered. Marked decrease in signal from the disc was observed after 2 weeks which did not recover till 2 years after chemonucleolysis. We suspect that the disc degenerated markedly after chemonucleolysis and changed into a type of scar tissue, maturation of which could stabilize the affected segment.

Adolescent↗
PubMed2004

Gene expression profile of degenerated cervical intervertebral disc tissues in rats.

OBJECTIVE: To analyze the gene expression profile of degenerated cervical intervertebral disc of Sprague Dawley rats on a large scale. METHODS: Degenerated models of Sprague Dawley rats of 9 months old (degeneration group, n=9) and normal Sprague Dawley rats of 3 months old (control group, n=9) were prepared, respectively. mRNA was obtained from the cervical intervertebral disc of rats in both groups, respectively, and then labelled by Cy5 and Cy3 fluorescence respectively after reverse transcription to obtain intervertebral disc cDNA probes. cDNA probes were hybridized with BiostarR-40s gene expression profile chips and scanned by laser scanner. The results were treated with portrait analysis, standardization management, and ratio analysis with softwares. RESULTS: Compared with the rats in the control group, 9.6% (381 pieces in total) gene expression changed obviously in the rats in the degeneration group, among which, the gene expression quantities of 171 pieces increased significantly (r=the ratio of the degeneration group to the control group>2.0), 52 pieces of which had certain function. While the gene expression quantities of 211 pieces decreased significantly (r<0.5), 41 pieces of which had certain function. CONCLUSIONS: Gene chip technology can be used to analyze the gene expression profile of degenerated intervertebral disc of rats in parallel, in quantity and on a large scale, which helps to testify the representative genes and protein expression, and plays an important role in clarifying the pathogenesis of degenerated intervertebral disc.

Animals↗
PubMed1976

Elastic fibers in human intervertebral discs.

Although previous studies failed to demonstrate elastic fibers in intervertebral discs, electron microscopy of twenty human intervertebral discs obtained at autopsy and operation revealed characteristic elastic fibers in both the annulus fibrosus and the nucleus pulposus. Their contribution to the mechanical properties of the intervertebral disc remains to be determined.

Adolescent↗
PubMedDate not supplied

Intervertebral disc abnormalities associated with vertebral metastasis: observations in patients and cadavers with prostatic cancer.

Abnormalities of intervertebral discs associated with vertebral metastasis from prostatic carcinoma are described in an investigation utilizing patient and cadaveric material. Radiographic and pathologic findings indicate that discal abnormality in this situation relates to three potential processes: intervertebral disc degeneration (intervertebral osteochondrosis); cartilaginous (Schmorl's) nodes; discal invasion by tumor. In most patients with vertebral metastasis, the adjacent intervertebral disc appears normal, a useful radiographic finding suggesting the presence of tumor rather than infection. Occasional patients with vertebral metastasis demonstrate roentgen abnormalities of the adjacent intervertebral disc indicating the occurrence of one or more of the above processes.

Humans↗
PubMed2005

[Effects of Yiqi Huayu Recipe on gene expression pattern of normal and apoptotic chondrocytes in cervical intervertebral disc in rats].

OBJECTIVE: To study the effects of Yiqi Huayu Recipe on the gene expression pattern in normal and apoptotic chondrocytes in the cervical intervertebral disc of rats. METHODS: The intervertebral disc endplates of rats were digested enzymatically. The apoptosis of the chondrocytes was induced by anti-Fas antibody. BiostarR-40s microarray chips were used to investigate the gene expression pattern in chondrocytes in the normal control, apoptosis and Yiqi Huayu Recipe groups. The results were scanned with Scan Array 4000 and analyzed with GenePix Pro 3.0, and then subjected to standardization and ratio analysis. RESULTS: In the apoptosis group, 30 kinds of genes expressed in cervical intervertebral disc chondrocytes were screened out, in which 10 were up-regulated (ratio>2) and 20 down-regulated (ratio<0.5) as compared with the normal control group. On the other hand, in the Yiqi Huayu Recipe group, 97 kinds of genes expressed in cervical intervertebral disc chondrocytes were screened out, in which 44 were up-regulated (ratio>2) and 53 down-regulated (ratio<0.5) as compared with the apoptosis group. CONCLUSION: There are some signal transduction pathways that control the apoptosis of the intervertebral disc chondrocytes. Yiqi Huayu Recipe regulates the gene express of the apoptotic chondrocytes in intervertebral disc. The study gives a further understanding to the mechanism of the cervical spondylosis and enriches the theories of qi and blood of traditional Chinese medicine.

Animals↗
PubMed1991

Immunohistochemical demonstration of sensory nerve fibers and endings in lumbar intervertebral discs of the rat.

Although it is accepted that the intervertebral disc has a sensory component, it has not been previously shown by any specific method. Immunoreactivity of the physiologically active neuropeptide, calcitonin gene-related peptide (CGRP), was used as a specific marker of sensory nerve fibers and their endings in the intervertebral disc of the rat. In this study, positive fiber immunoreactivity was taken as an indication that those fibers were of sensory, and not sympathetic, origin. Immunoreactivity was found in the outer annulus fibrosus of all intervertebral discs studied. The CGRP-like immunoreactivity was also found in structures that resembled nerve endings. To the authors' knowledge, this is the first report presenting detailed positive evidence of sensory fibers and their endings in the lumbar intervertebral disc of any mammalian species.

Animals↗
PubMed2006

Frequency of unexpected and important histopathological findings in routine intervertebral disc surgery.

OBJECT: The value of routine histopathological examination of intervertebral disc tissue has been questioned, but sufficient numbers of studies have yet to be conducted to provide a definitive sense of its importance. The aim of this study was to investigate the nature and frequency of unexpected histopathological findings in intervertebral disc surgery. METHODS: The authors conducted a retrospective examination of consecutive surgical specimens obtained in patients with benign indication for discectomy at four neurosurgical centers. Surgical specimens obtained during 2102 operations (2177 intervertebral discs) in 2017 patients were evaluated. In addition to one case of cavernous malformation, two specimens (obtained in 0.1% of patients) revealed unexpected pathological diagnoses of malignancy (metastasized prostate carcinoma and diffuse large B-cell lymphoma). CONCLUSIONS: The results of this retrospective study suggest that routine histopathological examination of specimens obtained during intervertebral disc procedures is both justified and cost effective.

Adult↗
PubMed1992

Cost-effectiveness analysis of extended conservative therapy versus surgical intervention in the management of herniated lumbar intervertebral disc.

The management of herniated lumbar intervertebral disc for patients not responding to an initial trial of conservative therapy is generally surgical. Little is known about the effect of continued conservative therapy on patients who have not improved or have deteriorated within the first 3 months. This study assessed which form of treatment, surgical or continued conservative therapy, is more cost-effective once an adequate trial of conservative therapy has failed. The study is a retrospective chart review of 55 white male truck drivers who presented with acutely herniated nucleus pulposus between 1985 and 1989. Twenty-five patients underwent surgery, and 30 underwent continued conservative therapy after initial rehabilitation. No significant difference was found in outcome (80% good or fair in both the surgical and conservative groups) or costs ($55,000 +/- $1,000/case during a 5-year period), hence no difference in the cost-effectiveness between the two treatment modalities (each $63,000 +/- $2,000/adjusted outcome). Conservatively treated patients, however, missed significantly more work. It was concluded that, for a patient not responding to the initial trial of conservative therapy, the option to undergo continued conservative treatment should be made available.

Adult↗