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A simple model for the function of proteoglycans and collagen in the response to compression of the intervertebral disc.

The nucleus pulposus of the intervertebral disc exerts a pressure which enables it to support axial compression when contained by the annulus fibrosus. The disc was modelled as a thick-walled cylindrical pressure vessel in which the nucleus was contained radially by the annulus. As a result, the stress in the annulus had radial (compressive) as well as tangential (tensile) components. The radial stress at a given point in the annulus was considered to be balanced by the internal pressure which is expected to arise from the attraction of water by proteoglycans. There was a reasonable agreement between the calculated radial stress distribution and published results on the distribution of water within the annulus. As the internal pressure is expected to be isotropic, the annulus was expected to contribute to the axial resistance to compression of the disc; this contribution would be equal, in magnitude, to the radial stress. Predictions of the pressure distribution within the annulus were similar to published experimental measurements made in the radial and axial directions. The tangential stress within the annulus was considered to arise from the restoring stress in its strained collagen fibrils.

Biomechanical Phenomena↗

Magnetic resonance evaluation of the intervertebral disc, spinal ligaments, and spinal cord before and after closed traction reduction of cervical spine dislocations.

STUDY DESIGN: A prospective clinical study using magnetic resonance imaging of the cervical spine in a consecutive series of patients with cervical spine dislocations. OBJECTIVES: To determine the incidence of intervertebral disc herniations and injury to the spinal ligaments before and after awake closed traction reduction of cervical spine dislocations. SUMMARY OF BACKGROUND DATA: Prior series in which the prereduction imaging of disc herniations in the dislocated cervical spine are described have been anecdotal and have involved small numbers of patients. In addition, no uniform clinical criteria to define the presence of an intervertebral disc herniation in the dislocated cervical spine has been described. The incidence of disc herniations in the unreduced dislocated cervical spine is unknown. METHODS: Eleven consecutive patients with cervical spine dislocations who met the clinical criteria for an awake closed traction reduction had prereduction and postreduction magnetic resonance imaging. Using strict clinical criteria for the definition of an intervertebral disc herniation, the presence or absence of disc herniation, spinal ligament injury, and cord injury was determined. Neurologic status before, during, and after the closed reduction maneuver was documented. RESULTS: Disc herniations were identified in 2 of 11 patients before reduction. Awake closed traction reduction was successful in 9 of the 11 patients. Of the nine patients with a successful closed reduction, two had disc herniations before reduction, and five had disc herniations after reduction. No patient had neurologic worsening after attempted awake closed traction reduction. CONCLUSIONS: The process of closed traction reduction appears to increase the incidence of intervertebral disc herniations. The relation of these findings, however, to the neurologic safety of awake closed traction reduction remain unclear.

Adolescent↗

Molecular therapy of the intervertebral disc.

Disc degeneration is the loss of the normal nucleus pulposus disc matrix to a more fibrotic and less cartilaginous structure. This change in disc micro-anatomy can be associated with pain and deformity, however, prevention and treatment options of disc degeneration are currently limited. Much research is going on to understand intervertebral discs at a molecular/ cellular level in hopes of creating clinically applicable options for treating disc degeneration. This review article will give insight into the current and developing status of treating intervertebral disc degeneration from a molecular standpoint.

Collagen↗

A feasibility study of in vivo T1rho imaging of the intervertebral disc.

PURPOSE: Recent studies have proposed that magnetic resonance (MR) T1rho relaxation time is associated with loss of macromolecules. The depletion of macromolecules in the matrix of the intervertebral disc may be an initiating factor in degenerative disc disease. The purpose of this study was to test the feasibility of quantifying T1rho relaxation time in phantoms and intervertebral discs of healthy volunteers using in vivo MR imaging at 3 T. MATERIALS AND METHODS: A multislice T1rho spiral sequence was used to quantify T1rho relaxation time in phantoms with different agarose concentrations and in the intervertebral discs of 11 healthy volunteers (mean age=31.3 years; age range=23-60 years; gender: 5 females, 6 males). RESULTS: The phantom studies demonstrated the feasibility of using spiral imaging at 3 T. The in vivo results indicate that the median T1rho value of the nucleus (116.6+/-21.4 ms) is significantly greater (P<0.05) than that of the annulus (84.1+/-11.7 ms). The correlations between the age of the volunteers and T1rho relaxation time in the nucleus (r2=-0.82; P=0.0001) and the annulus (r2=-0.37; P=0.04) were significant. A trend of decreasing T1rho values from L3-4 to L4-5 to L5-S1 was evident. CONCLUSION: The results of this study suggest that in vivo T1rho quantification is feasible and may potentially be a clinical tool in identifying early degenerative changes in the intervertebral disc.

Adult↗

Neuropeptides in the human intervertebral disc.

The innervation of the human intervertebral disc was investigated by immunochemical methods. Immunoreactivity to the general nerve marker protein gene product (PGP 9.5) was found in the outer annulus fibrosus of 11 of 12 discs removed during anterior arthrodesis for back pain. PGP 9.5-immunoreactive fibres ran between and across the collagenous lamellae, both in association with blood vessels and distant from them, and extended at least 3 mm into the disc. No innervation was observed in the nucleus pulposus. Fine fibres (< 1 micron in diameter) immunoreactive to calcitonin gene-related peptide and substance P (neuropeptides located in sensory and possibly nociceptive nerves) were identified in eight and four of the annuli fibrosi, respectively. Nerve fibres immunoreactive to vasoactive intestinal peptide and to the c-flanking peptide of neuropeptide Y were found in the majority of specimens of annulus fibrosus that were examined.

Adult↗

Gradient of mineral contents of vertebral column with special reference to intervertebral discs.

To study quantitatively the mineral elements in the vertebral column, we examined the vertebrae and intervertebral discs resected from three normal cadavers which died at middle age, by inductively coupled plasma atomic emission spectrometry. The relative contents of calcium, phosphorus, and sodium in vertebrae were high in the order from cervical to lumbar vertebrae. The ratios of calcium per phosphorus were 1.80 +/- 0.25 in cervical vertebrae, 1.59 +/- 0.22 in thoracic vertebrae, and 1.23 +/- 0.24 in lumbar vertebrae. The ratio of cervical vertebrae was the highest among them. In regard to intervertebral discs, both the relative contents of calcium and phosphorus were very much higher in the intervertebral discs between the 4th and 8th thoracic vertebrae than the others.

Bone Density↗

Positive feedback loop of interleukin-1beta upregulating production of inflammatory mediators in human intervertebral disc cells in vitro.

OBJECT: Interleukin-1beta (IL-1beta) induces neurological symptoms in intervertebral disc herniation (IDH). Recently, the existence of a positive feedback loop of IL-1beta, which encourages an inflammatory reaction or degeneration in the cells of tendon, has been reported. The authors hypothesized that there is a positive feedback loop of IL-1beta in the cells of IDH. METHODS: Eight human intervertebral disc specimens were harvested during spinal surgery for lumbar disc herniation. The cells were stimulated in serum-free medium with or without exogenous IL-1beta. The messenger RNA (mRNA) was extracted for reverse-transcription polymerase chain reaction (PCR) and real-time PCR to quantify the mRNA of endogenous IL-1beta, IL-6, cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs). The cells were then stimulated in serum-free medium with or without exogenous IL-1beta, and then exogenous IL-1beta was removed. After 2, 4, and 6 days, the medium was collected, and enzyme-linked immunosorbent assay was used to measure the protein concentration of endogenous IL-1beta. The mRNA expressions of endogenous IL-1beta, IL-6, COX-2, and MMPs were increased significantly depending on the concentration of exogenous IL-1beta. The protein concentration of endogenous IL-1beta was increased over time. CONCLUSIONS: There was a positive feedback loop of IL-1beta in the cells of IDH. Furthermore, the productions of IL-6, COX-2, MMP-1, and MMP-3 were upregulated as a result of the increasing concentration of IL-1beta in a positive feedback loop of IL-1beta. The authors concluded that this positive feedback loop of IL-1beta upregulated the production of mediators and thus can cause cessation of symptoms in IDH.

Adolescent↗

Outcome of one-level posterior lumbar interbody fusion for spondylolisthesis and postoperative intervertebral disc degeneration adjacent to the fusion.

STUDY DESIGN: Review of the clinical and radiologic records of patients who underwent one-level posterior lumbar interbody fusion (PLIF) at L4-L5. OBJECTIVE: To determine whether adjacent intervertebral disc degeneration after PLIF affects the clinical results, and whether preoperative caudal disc (L5-S1) degeneration affects postoperative clinical results. SUMMARY OF BACKGROUND DATA: There is little reliable information in the literature regarding clinical results and adjacent disc degeneration after PLIF. METHODS: Forty-five patients who underwent L4-L5 PLIF for spondylolisthesis with more than 5 years of postoperative observation were included in this study. PLIF was performed in conjunction with posterior instrumentation. The posterior lumbar intervertebral grafting was performed using both autograft and a ceramic spacer. Intervertebral disc heights at L2-L3, L3-L4, and L5-S1 were measured before and after surgery. The patients were divided into two groups based on the presence or absence of the preoperative L5-S1 narrowing. Correlation between clinical status evaluated by the recovery rate of the Japanese Orthopedic Association (JOA) score and disc heights were determined. RESULTS: All intervertebral disc heights adjacent to the fusion decreased after surgery (P < 0.05). However, no significant correlation was seen between clinical results estimated by the recovery rate and postoperative disc narrowing. There was also no significant difference in clinical results between patients with or without preoperative L5-S1 narrowing. CONCLUSIONS: There is no evidence from the results that postoperative narrowing of the adjacent disc and preoperative narrowing of the L5-S1 disc affects the clinical outcome of L4-L5 PLIF.

Adult↗

[Diagnosis and surgical management of Hangman's fracture combined with intervertebral disc injury].

OBJECTIVE: To study the pathology characteristics and management of Hangman's fracture combined with intervertebral disc injury. METHODS: Twenty-one patients suffered from this special injury were converged in this study. All patients underwent anterior C(2 - 3) discectomy and fusion, 18 cases were fixed by anterior cervical plate. The type of fractures, radiology characteristics, and clinical outcomes were investigated. RESULTS: No graft displacement or absorption, infection and neurologic deterioration occurred. All fresh dislocation of axis and C(2 - 3) angulation were corrected. Fusion of C(2 - 3) intervertebral space and pedicle fracture were acquired in all of the patients. After a mean follow-up of 31 months, ranging from 8 to 48 months, nearly all of the complains disappeared after operation. CONCLUSIONS: Hangman's fracture is not restricted at pedicle of the axis. Fracture combined with intervertebral disc injury is a special type of Hangman's fracture. Anterior discectomy and fusion of C(2 - 3) intervertebral disc is an effective operation method in accord with the pathophysiology of this special injury.

Adult↗

The changes in the intervertebral disc after chemonucleolysis demonstrated by magnetic resonance imaging.

Magnetic resonance imaging (MRI) of the spine produces images which reflect the chemical composition of the intervertebral disc. We have conducted a prospective study of the serial changes in the MRI appearance of the intervertebral disc after chemonucleolysis with the enzyme chymopapain. Fourteen patients were studied after single-level chemonucleolysis and the results compared with a control group of 17 discs in six patients who had diagnostic discography without enzyme insertion. A consistent pattern of gradual loss of signal from the nucleus pulposus culminating in complete loss of nuclear signal was seen in all cases after chemonucleolysis. Chymopapain therefore produced MRI changes analogous with premature gross disc degeneration. The rate at which this occurred varied; complete loss of signal took at least six weeks. Transitory minor end-plate changes were present in five patients, probably representing a mild chemical discitis. No similar changes were seen in the discography group.

Acute Disease↗

Biologic treatment for intervertebral disc degeneration: summary statement.

In past decades, the biomechanics of intervertebral disc degeneration have received much attention. More recent research efforts have focused on understanding the biology of the disc degenerative process. The ability to manipulate disc architecture and biology by direct application of growth factors or by gene therapy techniques may present an opportunity to halt or slow disc degeneration. Preliminary studies using these strategies have confirmed their ability to replenish essential disc matrix components that are known to decrease with disc degeneration.

Aging↗

A new method of creating intervertebral disc disruption of various grades.

BACKGROUND: The purpose of this study was to develop a model of intervertebral disc disruption capable of (1) internal disruption without excessive disruption to the disc surface, (2) user-defined disruption magnitude and location and (3) interrogation by magnetic resonance imaging. Present models of disc disruption may have some, but not all, of these features. METHODS: Intravenous tubes were inserted into the intervertebral discs of a cadaveric porcine lumbar spine. Tube placement in the inner annulus was confirmed by magnetic resonance imaging. Each disc was then injected through the intravenous tube with nitrogen gas at pressures of 69 kPa, 172 kPa, 345 kPa and 690 kPa. Before and after injection, edge detection analysis of magnetic resonance imaging images was used to quantify tissue disruption. These values were then multiplied by the thickness of the slices and summed to determine disruption volume for individual discs. Four additional discs were injected with the addition of ink, sectioned and then inspected visually. RESULTS: As the injection pressure increased, the gas volume within the annulus increased significantly as did visualized annular disruption. No significant difference in gas volume was observed between different discs injected with equal pressure. INTERPRETATION: As confirmed by magnetic resonance imaging and dissection, gas volume and tissue disruption within the annulus fibrosus were proportional to the pressure of injected nitrogen. This model of disc disruption promises to provide several advantages in the investigation of disc pathology including (1) user-controlled magnitude of inner annulus disruption, (2) user-controlled tissue disruption localization, (3) minimal disruption of the exterior annulus, (4) independence between the magnitude of external and internal disruption and (5) the ability to visualize resulting disruptions with magnetic resonance imaging.

Animals↗

[Correlation between shape and direction of small articular surface in lower lumbar vertebrae and degeneration of intervertebral disc].

To assess the possible correlation between the shape and the direction of the small articular surface in the lower lumbar vertebrae and the degeneration of the intervertebral disc, we investigated with computed tomography (CT) and evaluated with statistics the small articular surface and the transverse interface-joint angle (TIFA) of the L4-5 and the L5-S1 in 152 cases who had normal or degenerative discs verified through CT, MRI or operation. The small articular surface was found arc in 69.1% of the L4-5 and in 23.0% of the L5-S1. The TIFA of the L4-5 was less than that of the L5-S1. There was no correlation between the ratio of degeneration of the intervertebral disc at the L4-5 and the TIFA of the L4-5 and the L5-S1, but the ratio of degeneration of the intervertebral disc at the L5-S1 had postive correlation with the TIFA of the L4-5, negative correlation with the TIFA of the L5-S1, and particular correlation with the TIFA of the L5-S1 and L4-5. These results suggest that the shape and direction of the lower lumbar facet joint are related to the lumbar degeneration of intervertebral disc and the causes of degeneration at the L4-5 disc differ from those at the L5-S1 disc in biomechanics.

Adolescent↗

Innervation of the rabbit lumbar intervertebral disc and posterior longitudinal ligament.

STUDY DESIGN: The present study sought to determine to what extent the lumbar intervertebral disc and posterior longitudinal ligament are innervated in the New Zealand white rabbit. The intent is to use this disc model in future neurophysiology studies. OBJECTIVE: To characterize the distribution of nerve fibers and endings in the lumbar intervertebral disc and posterior longitudinal ligament in an animal model. SUMMARY OF BACKGROUND DATA: The results of previous disc innervation reports are somewhat conflicting regarding the density and depth of innervation into the anulus. METHODS: A silver impregnation technique was used to analyze sections from lumbar intervertebral disc and posterior longitudinal ligament of the New Zealand white rabbit. RESULTS: Numerous fine profiles of nerve fibers were demonstrated in the lumbar disc anulus and posterior longitudinal ligament. In the disc, the nerves were limited to the superficial anulus and anular surface. The nerve axons typically were 1 to 3 microns in diameter and were found around the entire periphery of the disc. No encapsulated endings were seen within the anulus, while occasional encapsulated endings were seen on the anular surface and posterior longitudinal ligament. CONCLUSION: This study demonstrates an extensive distribution of small nerve fibers in the size range of C and A-delta fibers throughout the peripheral anulus and provides an illustration of this distribution. These findings support a role for the disc as a source of low back pain.

Animals↗

Localization of cathepsins G and L in spontaneous resorption of intervertebral discs in a rat experimental model.

To determine the involvement of cathepsins G and L in the mechanism of spontaneous resorption of herniated intervertebral discs, localization of these cathepsins in this process was examined immunohistochemically using a rat model of autologous transplantation of coccygeal discs. Rat coccygeal discs were resected and autotransplanted into the subcutaneous space of the skin of the back. Paraffin-embedded sections of intervertebral disc tissue, harvested at various post-transplantational periods, were immunohistochemically stained with antibodies for cathepsin G, cathepsin L, MMP-1, MMP-3 and ED-2. The number of positive cells was counted in each part of the transplanted discs. Immunolocalization of cathepsins G and L in various types of disc cells was first observed early in the post-transplantation period. From two days after the operation, histology showed invasion by granulation tissue, with many macrophages, in all sections. Subsequently, the number of macrophages in granulation tissue was observed to increase, along with a gradual increase in the percentage of cells positive for MMP-1 and MMP-3. In addition to the ability of cathepsins G and L to degrade major extracellular matrix components of intervertebral discs, cathepsin G is capable of activating latent pro-MMPs. The up-regulation of cathepsins G and L in the intervertebral disc tissue in this spontaneous resorption model suggests that these proteinases may be involved in degradation of extracellular matrix, leading to the natural resorption of herniated discs.

Journal Article↗

Identification of heterogeneous cell populations in normal human intervertebral disc.

There is clear evidence that tissues related to the intervertebral disc, such as articular cartilage, contain several phenotypically different chondrocytic cell populations. Histological data for the disc suggest the same may be true for the annulus fibrosus and nucleus pulposus, but this has not been shown directly. For the first time, cells from adult human nondegenerative nucleus pulposus and annulus fibrosus were recovered after enzymatic digestion and maintained in an alginate bead culture system for up to 6 wk. The cells remained viable and produced matrix, but did not divide. Cultured cells were stained simultaneously for the presence of chondroitin sulphate and keratan sulphate, or types I and II collagen. The majority of the cells from both the annulus fibrosus and the nucleus pulposus produced both keratan sulphate and chondroitin sulphate (> 60%), a few only detectable levels of one or the other, but a significant population produced neither. This is an indication of a population of cells with a nonchondrocytic phenotype. In nondegenerative discs, the majority of the annulus fibrosus cells produced both types I and II collagen but the majority of nucleus pulposus cells produced only type II collagen. These observations are consistent with the presence of at least 2 phenotypically stable populations of cells in the adult human intervertebral disc and with the view that the phenotype of the major population of the annulus is different from that of the nucleus.

Adult↗

[Controlled distraction as a therapeutic option in moderate degeneration of the intervertebral disc -- an in vivo study in the rabbit-spine model].

AIM: The aim of this study was to investigate the effects of temporary distraction on a degenerated intervertebral disc to characterize regenerative changes associated with disc distraction. METHOD: New Zealand white rabbits (n = 32) were used for this experimental animal study. The rabbits were randomly assigned to one of five groups. 6 animals were loaded for 28 days using a custom-made external loading device to stimulate disc degeneration (G2). In 6 animals the discs were first loaded for 28 days and after 28 days loading time the discs in six animals were treated as dynamic distraction with an external distraction device (G1). In six animals the discs were distracted for 28 days without previous loading (G5) and in six animals the discs were loaded for 28 days and afterwards the loading device was removed for 28 days for recovery without distraction (G3). Six animals were sham operated (G4) without application of axial load. After 28 to 56 days loading and distraction time, the animals were sacrificed and the lumbar spine was harvested for histological and radiographic analysis. Histology was performed according to a degeneration score and disc height was calculated radiographically. For the cell viability examination, the number of apoptotic cells was determined. RESULTS: After 28 days of loading (G2), the discs showed a significant decrease in disc space of the treated segment. Histologically, a disorganization of the architecture of the annulus occurred. The number of dead cells increased significantly in the annulus and cartilage endplate. These changes were reversible after 28 days of distraction (G1). The disc thickness increased significantly to physiological levels as compared to the specimens from the 28 days loading group without distraction. Histologically, the discs showed signs of tissue regeneration after 28 days of distraction (G1). The number of apoptotic cells decreased significantly in comparison to the loaded discs without distraction (G2). CONCLUSION: The results of this study suggest that disc regeneration can be induced by axial dynamic distraction in the moderately degenerated rabbit intervertebral disc. The decompressed rabbit intervertebral discs showed signs of tissue recovery at the cellular and histological levels after temporary disc distraction.

Animals↗