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PubMed1997

The role of phospholipase A2 and nitric oxide in pain-related behavior produced by an allograft of intervertebral disc material to the sciatic nerve of the rat.

STUDY DESIGN: To elucidate the pathomechanisms of radicular pain secondary to lumbar disc herniation. OBJECTIVES: To evaluate whether intervertebral disc material applied to the sciatic nerve produces hyperalgesia, and if the hyperalgesia in influenced by inhibitors of phospholipase A2 and nitric oxide synthase. SUMMARY OF BACKGROUND DATA: Previously, the authors reported that application of nucleus pulposus and anulus fibrosus material to the lumbar epidural space produces different forms of hyperalgesia (mechanical versus thermal), with different and distinct histologic changes. Additional pharmacologic studies showed that phospholipase A2 and nitric oxide are involved in the mechanisms that produce the mechanical and thermal hyperalgesia, respectively, N omega-nitro-L-arginine methyl ester and mepacrine are relatively selective inhibitors of nitric oxide synthase and phospholipase A2, respectively. However, it is not known what the relation is between the hyperalgesia produced and the activation and involvement of phospholipase A2 and production of nitric oxide, or why the application of nucleus pulposus and nucleus pulposus with anulus fibrosus produces different types of hyperalgesia. METHODS: Experiments were performed in five groups of rats: The control group (no treatment), the sham group (exposure of the sciatic nerve only), the fat group (allografted fat on the sciatic nerve), the nucleus pulposus group (allografted nucleus pulposus) and the nucleus pulposus + anulus fibrosus group (allografted nucleus pulposus and anulus fibrosus). Withdrawal threshold and latency from mechanical pressure and a radiant heat to hind paws were measured preoperatively and postoperatively. After local sciatic nerve administration of N theta-nitro-L-arginine methyl ester or mepacrine into the operated site, sensitivities to noxious stimuli were reevaluated after treatment. RESULTS: Only rats in the nucleus pulposus group showed evidence of mechanical hyperalgesia. However, injection of N theta-nitro-L-arginine methyl ester resulted in evidence of mechanical hyperalgesia in the nucleus pulposus + anulus fibrosus group. Mechanical hyperalgesia was produced in the nucleus pulposus group and after injection of N theta-nitro-L-arginine methyl ester in the nucleus pulposus+anulus fibrosus group, both of which returned to normal after mepacrine injection. There were no significant changes in sensitivity to thermal stimuli in any of the experimental groups. CONCLUSION: It appears that phospholipase A2 and nitric oxide play important but different roles in pathomechanisms of radicular pain in lumbar disc herniation.

Animals↗
PubMed1990

Herniated intervertebral discs associated with unstable spinal injuries.

To examine the occurrence of traumatic herniated intervertebral discs associated with unstable spinal injuries, the authors reviewed the records of all patients with spinal cord level unstable spine injuries managed at their institution over a 26-month period. Ninety-three patients were identified. All patients had roentgenographic and computed tomographic (CT) evaluation. Magnetic resonance imaging was performed in 48 patients, and revealed the presence of a herniated intervertebral disc in 16, with the highest incidence being in the cervical spine. In the patients who had only plain film and CT scans, no disc pathology was identified. Magnetic resonance imaging provides a noninvasive means of examining intervertebral disc damage in unstable spinal injuries that might otherwise be unidentified and result in spinal cord injury at the time of surgery.

Adult↗
PubMed2006

Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs.

While there is consensus in the literature that blood vessels are confined to the outer anulus fibrosus of normal adult intervertebral disc, debate continues whether there is a vascular in-growths into inner parts of the intervertebral disc during degeneration. We therefore tested the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. The specific endothelial cell marker CD 31 (PECAM) was used to immunohistochemically investigate 42 paraffin-embedded complete mid-sagittal human intervertebral disc sections of various ages (0-86 years) and varying extent of histomorphological degeneration. Additionally, 20 surgical disc samples from individuals (26-69 years) were included in this study. In discs of fetal to infantile age, blood vessels perforated the cartilaginous end plate and extended into the inner and outer anulus fibrosus, but not into the nucleus pulposus. In adolescents and adults, no blood vessels were seen except for the outer zone of the anulus fibrosus adjacent to the insertion to ligaments. The cartilaginous end plate remained free of vessels, except for areas with circumscribed destruction of the end plate. In advanced disc degeneration, no vessels were observed except for those few cases with complete, scar-like disc destruction. However, some rim lesions and occasionally major clefts were surrounded by a small network of capillary blood vessels extending into deeper zones of the anulus fibrosus. A subsequent morphometric analysis, revealed slightly "deeper" blood vessel extension in juvenile/adolescent discs when compared to young, mature and senile adult individuals with significantly "deeper" extension in the posterior than anterior anulus. The analysis of the surgical specimens showed that only sparse capillary blood vessels which did not extend into the nucleus pulposus even in major disc disruption. Our results show that vascular invasion deeper than the periphery was not observed during disc degeneration, which supports the hypothesis that vascular in-growth is not a distinct feature of disc degeneration.

Adolescent↗
PubMed1990

Histological changes in aging lumbar intervertebral discs. Their role in protrusions and prolapses.

To study the relationships between the changes due to aging in lumbar intervertebral discs and the development of protrusion or prolapse, we carried out histological studies on operative specimens of thirty-one discs, of which twenty-two had been protruded and nine, prolapsed. The specimens were obtained during twenty-nine operations for herniation of a lumbar intervertebral disc in patients who were sixty years old or older. Changes in the anulus fibrosus were more extensive in the nine prolapsed discs than in the twenty-two protruded discs. Of the nine prolapsed discs, myxomatous degeneration, fibrosis, and swollen anular fibers were found in all nine, and cysts were seen in five. Of the twenty-two protruded discs, only five showed myxomatous degeneration; ten, fibrosis; one, a cyst; and sixteen, swollen fibers. For comparison, we also studied specimens that had been obtained at operation from twenty-one other patients, twenty to fifty-nine years old, who had a prolapsed disc. The anulus showed myxomatous degeneration in all twenty-one specimens, cysts in eight, and fibrosis in ten. In addition, we examined 368 autopsy specimens from people who had been between twenty-five and eighty-five years old at the time of death. In many of the subjects who had died in the sixth decade of life or later, we found that the orientation of the inner fiber bundles of the anulus fibrosus was reversed, so that they bulged inward. The reversal appeared to be the result of myxomatous degeneration of the middle fibers of the anulus, atrophy of the nucleus, and narrowing of the disc space. These histological findings suggest explanations for the predominance of protrusions of the nucleus pulposus in patients who are less than sixty years old and of prolapse of the anulus fibrosus in the few patients who are more than sixty years old who have herniation of an intervertebral disc.

Adolescent↗
PubMed1994

Gadolinium-enhancement characteristics of magnetic resonance imaging in distinguishing herniated intervertebral disc versus scar in dogs.

STUDY DESIGN: This study is an experimental investigation on the gadolinium contrast magnetic resonance imaging (MRI) in distinguishing sequestered disc fragment versus scar in dogs. The conspicousness of the disc fragment and signal intensities of the disc fragment and laminectomy scar were evaluated using gadolinium-enhanced MRI and histology. OBJECTIVES: This study investigated the effects of timing of gadolinium injections, gadolinium doses, and aging of scar or disc on the enhancement characteristics and conspicuousness of disc fragment in MRI. SUMMARY OF BACKGROUND DATA: Contrast-enhanced MRI has been frequently used as a procedure to evaluate patients with suspected recurrent herniated discs. In contrast-enhanced MRI, the postoperative scar tissue enhances to a greater extent than disc fragments. Previous reports suggest different contrast enhancement characteristics of scar depending on doses, timing of gadolinium, or maturity of scar. There are different compounds of gadolinium agents and different doses are becoming available. There is no previous report on the evaluation of gadolinium enhancement characteristics in dogs with concurrent herniated disc and scar. METHODS: Six conditioned Beagle dogs underwent hemilaminectomies and discectomies at the L3-L4 level. An autogenous disc fragment was obtained from the intervertebral disc of the tail. This disc fragment was placed anterolateral to the thecal sac, simulating a sequestered disc herniation. Three control animals underwent hemilaminectomies and discectomies alone. Each dog underwent MRI on a 1.5 Tesla scanner (3.0 mm slice in sagittal and axial projections with TR 500, TE 30 msec and high dose 0.3 mmol/kg of gadoteridol). Images were obtained at 15 days, 30 days, 60 days, and 90 days after surgery. At each imaging session, contrast enhancement was measured at 2 minutes, 25 minutes, and 45 minutes after gadolinium injection for kinematic analysis. Two animals at a time were killed on 30 days, 60 days, and 90 days postoperatively. Magnetic resonance imaging was done with conventional low dose 0.1 mmol/kg of gadopentetate at 15 days and before death. RESULTS: Results revealed that the difference of enhancement between disc and the scar and therefore conspicuousness of disc fragment was greater on 2-23-minute images as compared with 45- minute images, and the distinction decreased with aging of the scar. The high dose contrast-enhanced MRI increased signal intensities for both disc and scar. Conspicuousness of disc fragment seemed to be better with the high-dose gadolinium compound. CONCLUSIONS: In conclusion, contrast enhancement characteristics in MRI may depend on the timing of MRI after gadolinium injection, doses of gadolinium, and aging of scar or disc.

Animals↗
PubMed1991

Immunolocalisation of type VI collagen in the intervertebral disc.

Type VI collagen has been isolated from many connective tissues, including the intervertebral disc. Distribution of this collagen, however, varies considerably within different tissues. In adult mammalian nasal and articular cartilage it is localised preferentially in the matrix immediately surrounding the cell. Intervertebral discs from various species and of various ages were studied and a similar pericellular localisation was found. When antisera to type VI collagen were used staining was seen around the cells of all sections of intervertebral disc, being particularly prominent in the nucleus pulposus. Staining on or around the cells was also seen in the adjacent cartilaginous end plate and bone.

Adult↗
PubMed2003

Effect of dynamic hydrostatic pressure on rabbit intervertebral disc cells.

The pathogenesis of vibration-induced disorders of intervertebral disc at the cellular level is largely unknown. The objective of this study was to establish a method to investigate the ranges of constructive and destructive hydrostatic loading frequencies and amplitudes in preventing or inducing extracellular disc matrix degradation. Using a hydraulic chamber, normal rabbit intervertebral disc cells were tested under dynamic hydrostatic loading. Monolayer cultures of disc outer annulus cells and 3-dimensional (3-D) alginate cultures of disc nucleus pulposus cells were tested. Effects of different loading amplitudes (3-D culture, 0-3 MPa; monolayer, 0-1.7 MPa) and frequencies (1-20 Hz) on disc collagen and protein metabolism were investigated by measuring 3H-proline-labeled proteins associated with the cells in the extracellular matrix and release of 3H-proline-labeled molecules into culture medium. High frequency and high amplitude hydrostatic stress stimulated collagen synthesis in cultures of outer annulus cells whereas the lower amplitude and frequency hydrostatic stress had little effect. For the same loading duration and repetition, neither treatment significantly affected the relative amount of protein released from the cell layers, indicating that protein degradation and stability were unaffected. In the 3-D nucleus culture, higher amplitude and frequency increased synthesis rate and lowered degradation. In this case, loading amplitude had a stronger influence on cell response than that of loading frequency. Considering the ranges of loading amplitude and frequency used in this study, short-term application of high loading amplitudes and frequencies was beneficial in stimulation of protein synthesis and reduction of protein degradation.

Animals↗
PubMed1989

Intradural herniation of a lumbar intervertebral disc.

Intradural disc herniation of an intervertebral disc is a rare occurrence. The clinical presentation varies in severity and a high level of suspicion is necessary to determine the diagnosis. This is a case report of an intradural disc herniation in a young male. A review of the literature identifying the pathophysiologic mechanisms of intradural disc herniation, diagnostic imaging techniques, and treatment is presented.

Adult↗
PubMed2000

Direction-dependent constriction flow in a poroelastic solid: the intervertebral disc valve.

We hypothesize that a direction-dependent flow resistance exists in the intervertebral disc due to constriction flow in the cartilage endplates. A comparison of the hydrostatic pressure in the nucleus of the healthy intervertebral disc during daily loading with the relatively low osmotic swelling pressure during rest, suggests the necessity of such direction-dependent flow resistance to ensure that all the fluid exuded from the disc during loading is recovered during rest. A physical model demonstrating the direction-dependent resistance of constriction flow in a poroelastic solid is presented. A finite element model was developed and validated against this physical model. The finite element model showed that decrease of the constriction hole area not only increases the resistance to fluid flow, but also causes the direction-dependency of flow resistance to decrease. Through this mechanism, endplate sclerosis could affect normal daily fluid exchange in the intervertebral disc, resulting in decreased mass transport and/or dehydration of the disc.

Biological Transport↗
PubMed1999

An in vivo magnetic resonance imaging study of changes in the volume (and fluid content) of the lumbar intervertebral discs during a simulated diurnal load cycle.

STUDY DESIGN: Magnetic resonance imaging was used to measure the changes in volume of the lumbar intervertebral disc in vivo during a load cycle. OBJECTIVES: To measure changes in volume of the lumbar intervertebral disc during a load cycle and relate these changes to changes in fluid content. SUMMARY OF BACKGROUND DATA: There have been very few experiments conducted to measure the volume and fluid changes in intervertebral discs in vivo. METHODS: Five healthy subjects were recruited (aged 27, 29, 31, 34, and 52 years) in a study using magnetic resonance imaging to measure the changes in volume of the lumbar intervertebral disc in vivo, during a load cycle. The experiment was designed to simulate a diurnal load cycle, but over less time. The load cycle consisted of bed rest, followed by walking with a 20-kg backpack for 3 hours, followed by bed rest for 3 hours. Magnetic resonance imaging scans of the lumbar spine were obtained 10 times during this load cycle. The disc volume was calculated by summing the disc area contained in each slice of the scan. The changes in volume of the discs (L2-L3, L3-L4, and L4-L5) recorded at the 10 times were then related to the fluid changes. RESULTS: Load-induced changes in disc volume can be detected and measured using MR imaging. The average volume increase 3 hours after removing a highly compressive load was 5.4%. The water content of the nucleus and anulus in the disc of the young human is said to be approximately 80% and 70%, respectively. If the disc gained 5.4% of its initial total volume, and assuming that the initial fluid content was approximately 75%, then it gained approximately 7% (i.e., 5.4%/75% x 100% approximately 7%) of its fluid. CONCLUSIONS: Load-induced changes in disc volume can be detected and measured using magnetic resonance imaging.

Adult↗
PubMedDate not supplied

Design and evaluation of the FlexiCore metal-on-metal intervertebral disc prosthesis.

BACKGROUND CONTEXT: The technical difficulties associated with the development of an intervertebral disc prosthesis include endurance demands on the device, lack of consensus concerning the biomechanical principles governing the articulation of the spinal joint and the performance of materials available for implantation. PURPOSE: Although biologically based disc prostheses and augmentations may be the endpoint of spinal disc replacements, these devices and associated technologies will still require decades of work in order to achieve fruition. The more immediate solution will require a durable, biocompatible device capable of restoring range of motion. The evaluation of such a device must include failure testing of critical components as well as a series of fatigue experiments under overloaded conditions. STUDY DESIGN/SETTING: Recent literature citing adjacent level degeneration associated with segmental mobilization and a lack of correlation between successful fusion and clinical success has prompted the need for a dynamic intervertebral disc prosthesis. METHODS: Combined with a better understanding of the biomechanics and the prospect of an increasing percentage of more elderly patients, the future of spinal fusion for pain and instability may need to be reexamined. The authors propose a novel metal-on-metal design for an intervertebral device that features a fixed center of rotation, a mechanical torsional limit, a unique feature to allow for the location of the device in a patient-specific manner, and means by which the device may be implanted directly anterior or anterolaterally. RESULTS: Physiological ranges of motion are retained by the prosthesis. In addition, initial and long-term fixations are achieved through spines and bone ingrowth coating. The device comprises a retained ball and socket positioned between two baseplates. The ball and socket joint permits articulation through the appropriate physiological range of motion and center of rotation as the baseplates provide a stable platform for implantation. CONCLUSIONS: An intervertebral disc prosthesis has been designed and has demonstrated mechanical performance beyond what is required physiologically under preliminary testing.

Alloys↗
PubMed1985

Anatomical basis of intervertebral disc puncture with chemonucleolysis.

Transparietal puncture of the lumbar intervertebral discs is done to achieve enzymatic nucleolysis. This technique requires firm understanding of the morphology and topography of the anatomical structures traversed by the needle as well as those to be avoided. Vertebral disc puncture with chemonucleolysis has been done by the author for four years. The aim of this study was to identify the parameters allowing facilitation of this procedure, thereby leading to a decreased X-ray exposure. To achieve this goal an analytical study of the target structure and its neurovascular, osseous and visceral relations was carried out. The results of this study led to practical conclusions regarding especially the parameters of disc puncture, their preoperative identification and the risks encountered in case of erroneous puncture.

Chymopapain↗
PubMed1993

Neutral proteinases in human intervertebral disc. Role in degeneration and probable origin.

Neutral proteinases were partially purified from human intervertebral disc by extraction with guanidine hydrochloride followed by Sephadex G-75 column chromatography. They showed gelatinolytic and elastolytic activities at neutral pH. The apparent molecular weights of these enzymes were 70 KD and 25 KD, the former being the complexed form of the latter. The sensitivity to various synthetic inhibitors indicated these enzymes to be serine elastases. Furthermore, they were considered to be leukocyte elastases because anti-leukocyte elastase antibody inhibited the proteinase activity of these enzymes. Proteinase activity was not detected in normal discs, except for some slight activity in the end-plate. In contrast, the degenerated discs showed high activity, especially in the nucleus pulposus and end-plate. Similar high levels of proteinase activity were found in the vertebral body adjacent to normal as well as degenerated discs. These findings suggest that leukocyte elastase, which is normally present in the vertebral body, flows into and degrades the matrix of the intervertebral disc under pathologic conditions.

Adolescent↗
PubMed2005

Immunohistochemical demonstration of lumbar intervertebral disc innervation in the dog.

Low back pain is a common ailment in dogs, particularly in specific breeds such as the German shepherd dog. A number of structures such as facet joint capsules, ligaments, dorsal root ganglia, periosteum, vertebral endplates and meninges have been associated with this condition. Yet, in spite of all diagnostic efforts, the origin of pain remains obscure in a substantial proportion of all cases. A further structure often being involved in vertebral column disorders is the intervertebral disc. The presence of nerves, however, is a precondition for pain sensation and, consequently, structures lacking innervation can be left out of consideration as a cause for low back pain. Nerve fibres have been demonstrated at the periphery of the intervertebral disc in man, rabbit and rat. With regard to the dog, however, the extent of intervertebral disc innervation is still being disputed. The goal of the present study, therefore, was to substantiate and expand current knowledge of intervertebral disc innervation. Protein gene product (PGP) 9.5 was used for immunohistochemical examination of serial transversal and sagittal paraffin sections of lumbar discs from adult dogs. This general marker revealed nerve fibres to be confined to the periphery of the intervertebral discs. These results indicate that even limited pathological processes affecting the outer layers of the intervertebral disc are prone to cause low back pain.

Animals↗
PubMedDate not supplied

Cell-based tissue engineering for the intervertebral disc: in vitro studies of human disc cell gene expression and matrix production within selected cell carriers.

BACKGROUND CONTEXT: Little is known about how disc cells attach, proliferate and form extracellular matrix (ECM) within carrier materials. Such information is needed to help formulate criteria for successful cell-carrier interactions in tissue engineering. PURPOSE: To compare proliferation, ECM production and gene expression in annulus cells cultured in a variety of cell carrier materials with potential application in tissue engineering of the disc. STUDY DESIGN: Human intervertebral disc cells from the annulus were used in a prospective study of proliferation, ECM production and gene expression within selected cell carriers. METHODS: Annulus cells from discs of 29 individuals were tested in collagen sponge, collagen gel, agarose, alginate or fibrin gel formulations. In situ hybridization assessed ECM gene expression of Types I and II collagen, aggrecan and chondroitin-6 sulfotransferase. Cell proliferation, cell shape, attachment and ECM production were evaluated. RESULTS: Collagen sponges provided the best microenvironment for disc cell ECM production and gene expression. Although collagen gels often could support good cell growth, such constructs did not result in either abundant ECM production or ECM gene expression, as shown by in situ hybridization. Growth and ECM production and gene expression in alginate, agarose and fibrin microenvironments were inferior. CONCLUSIONS: Tissue engineering techniques open new therapeutic possibilities for use of autologous disc cells, but fundamental questions on how these cells interact with cell carriers are unexplored. Results provide novel data on disc cell gene expression within diverse microenvironments. The collagen sponge proved to be a superior microenvironment.

Absorbable Implants↗
PubMed2001

Histology of intervertebral disc protrusion: an experimental study using an aged rat model.

STUDY DESIGN: In vitro experimental intervertebral disc ruptures of aged rats were examined histologically. OBJECTIVES: To clarify the mechanism of intervertebral disc herniations by microscopic investigation of ruptured discs. SUMMARY OF BACKGROUND DATA: Clinically, disc herniations have been classified into two types: extrusion and protrusion. However, the pathogenesis of protrusion type herniations has not yet been demonstrated by any studies. To clarify this issue, it is essential to establish an appropriate model producing disc herniations, and to examine the sequential changes in the structure of herniated discs. METHODS: Lumbar discs of 2-year-old rats were examined histologically and compared with human lumbar discs. To examine structural changes in discs subjected to repetitive motion stress, 400 repetitions of a sequence of flexion (30 degrees ) and axial rotation (6 degrees ) were applied in vitro to the lumbar discs of the animals. RESULTS: The microstructure of normal lumbar discs in aged rats was similar in many ways to the human lumbar discs in a 20- to 40-year-old adult. Of 10 discs subjected to repetitive stress, 4 were ruptured at the junction between the posterior anulus fibrosus and the sacral cartilage endplate. One had an extruded nucleus pulposus, and three had a protruded anulus fibrosus, which displayed disorganized structure containing widened and flaccid lamellae. CONCLUSIONS: The results from this study indicate that disc protrusion can be caused by disorganization of the ruptured annular lamellae, not by focal compression of the nucleus pulposus.

Adult↗
PubMed1988

Metaplastic proliferative fibrocartilage as an alternative concept to herniated intervertebral disc.

It is hypothesized on the basis of experimental intervertebral disc degeneration that herniated disc is actually newly synthesized proliferative metaplastic fibrocartilage and not herniation of pre-existing disc tissue, particularly that of the nucleus pulposus. Human material in selected surgical tissues was examined to test this concept. Histology revealed evidence for proliferative fronts of fibroblastic cells in herniated discs with hypocellular interiors. Hydroxypyridinium cross-link assay was used to determine the maturity of the collagen. Results indicated, with statistical significance, that herniated disc is a younger tissue than in situ annulus fibrosis, and that herniated disc is not from the nucleus pulposus, thus supporting the hypothesis.

Adult↗
PubMed1997

Lumbar intervertebral disc herniation in children less than 16 years of age. Long-term follow-up study of surgically managed cases.

STUDY DESIGN: In this retrospective study, the long-term clinical results of lumbar intervertebral disc herniation in children less than 16 years of age were reviewed. OBJECTIVES: To evaluate the effectiveness of surgical treatment including posterior discectomy, extraperitoneal anterolateral discectomy, and anterior interbody fusion for lumbar intervertebral disc herniation in children less than 16 years of age. SUMMARY OF BACKGROUND DATA: Although previous follow-up studies on surgically managed lumbar intervertebral disc herniation in children and adolescents generally reveal good outcomes, few reports have focused on the time course of clinical findings and the long-term results. METHODS: The outcome of subjective symptoms, clinical signs, and time-related change of the intervertebral disc space in 11 patients were evaluated with an average follow-up period of 9 years (range, 5-12 years). RESULTS: The posterior discectomy procedure relieved clinical symptoms quickly. In the case of central herniation with or without intervertebral instability, extraperitoneal anterolateral discectomy or anterior interbody fusion led to favorable long-term results. Clinical symptoms (lower back pain, leg pain) and neurologic disturbance disappeared within 3 months after surgery. Recovery of normal straight leg raising test results (tight hamstrings), however, required much more time than recovery of other symptoms. Narrowing of the intervertebral disc space progressed up to 3-6 months after discectomy, but then disc space widening occurred. CONCLUSIONS: Satisfactory long-term clinical results and early return to school life were obtained with each surgical procedure. It is important to aim toward an early return to school via surgical treatment.

Adolescent↗