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Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats.

STUDY DESIGN: The authors studied the origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats by resection of the sympathetic trunks. OBJECTIVE: To understand discogenic low back pain from the innervation of the lumbar intervertebral discs. SUMMARY OF BACKGROUND DATA: The afferent pathways of discogenic low back pain have not been studied thoroughly. It has been reported that stimulation of an inflamed lower spinal nerve root elicits leg pain but not low back pain and that stimulation of the posterior portion of lumbar intervertebral discs evokes only low back pain. These facts suggest that pain sensation from the posterior portion of lumbar discs is not transmitted via the lower spinal nerve roots. METHODS: Forty-five Wistar rats were used. Seven days after the resection of sympathetic trunks with ganglia at different levels, the whole lumbar spine was stained by an acetylcholinesterase histochemical method. The posterior portions of lumbar intervertebral discs were observed. RESULTS: The dense nerve network on the posterior portion of lumbar intervertebral discs had disappeared almost completely after total resection of bilateral sympathetic trunks at L2-L6. However, there was a slight decrease in the network after bilateral single-level resection or unilateral multisegmental resection. CONCLUSIONS: The results showed that the posterior portion of lumbar intervertebral discs was innervated by the sympathetic nerves multisegmentally and bilaterally.

Afferent Pathways↗

Two-level intervertebral disc herniation in an adolescent.

A two-level intervertebral disc prolapse is a rare circumstance in adolescents. We describe the case of a 19-year-old man who suffered a deceleration traum and developed simultaneous large intervertebral disc herniations at L4/5 and L5/S1. The aetiology is discussed and, in accordance with the current literature, it is pointed out that clinical findings due to intervertebral disc herniations in young people do not necessarily correspond with the extent of the disease.

Accidents, Occupational↗

Proteoglycans of human infant intervertebral disc. Electron microscopic and biochemical studies.

The ground substance of the intervertebral disc consists primarily of proteoglycans, which give the tissue its stiffness to compression and its resiliency. To investigate the structure and composition of these molecules, we extracted them from human infant nucleus pulposus under associative conditions and from human infant annulus fibrosus and cartilage end-plate under dissociative conditions. We examined the degree of aggregation, the composition, the electron microscopic appearance, and the dimensions of the proteoglycans of the intervertebral disc and compared their structure and dimensions with those of the proteoglycans from bovine hyaline cartilage. Aggregates represented 52 per cent of the proteoglycans of the nucleus pulposus between the ages of one and ten days but only 28 per cent between the ages of six and eight months. Preparations from the corresponding annuli contained 59 per cent aggregates at one to ten days and 47 per cent at six months. The corresponding cartilage end-plate preparations contained 45 and 40 per cent aggregates. The proteoglycans of the annulus fibrosus and cartilage end-plate contained more protein and less hexosamine than did those of the nucleus pulposus. Electron microscopy showed that approximately two-thirds of the aggregates from nucleus pulposus consisted of very short hyaluronate filaments with closely packed monomers. The other third had longer hyaluronate filaments and wider distances between monomers, and closely resembled the aggregates from the annulus fibrosus and cartilage end-plate. Aggregated monomers consisted of two segments: a thin segment connecting directly to the hyaluronic acid filament and a thick segment extending peripherally from the thin segment. The thin segment formed about 12 per cent of the total monomer length in the samples from all three disc tissues. The lower proportion of aggregated monomers, the lower protein content, and the smaller aggregates with closely packed monomers suggest that the nucleus pulposus may contain less link protein than do the annulus fibrosus and cartilage end-plate. Compared with proteoglycan aggregates from bovine hyaline cartilage, proteoglycan aggregates from human intervertebral disc were shorter and had fewer monomers and wider spacing between monomers. The aggregated monomers from the three components of the intervertebral disc had an average length of 209 +/- 90 nanometers, compared with 210 +/- 114 nanometers for monomers from hyaline cartilage of skeletally mature cows, 250 +/- 116 nanometers for monomers from hyaline cartilage of skeletally immature calves, and 288 +/- 108 nanometers for monomers from fetal animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Cartilage↗

Does long-term compressive loading on the intervertebral disc cause degeneration?

STUDY DESIGN: Coil springs were stretched and attached to produce a compressive force across the lumbar intervertebral discs of dogs for up to 53 weeks. OBJECTIVE: To test the hypothesis that compressive forces applied to the intervertebral disc for a long period of time cause disc degeneration in vivo in a dog model. SUMMARY OF BACKGROUND DATA: It is a commonly held belief that high forces applied to the intervertebral disc, and to joints in general, play a role in causing degeneration. METHODS: Coil springs were stretched and attached to produce a compressive force across the lumbar intervertebral discs (L3/L4) of 12 dogs. After up to a year, the dogs were killed, and their lumbar spines were removed and radiographed. The L3/L4 disc and the controls (T13/L1 and L4/L5) were excised and examined for visible signs of degeneration. The discs then were assessed using immunohistochemical analysis and enzyme-linked immunosorbent assay. Disc chondrocytes also were assayed for apoptosis. RESULTS: No obvious signs of degeneration in the discs (L3/L4) that had been under compression for up to a year could be observed. There was no disc bulging, anular fissures, or disc space narrowing. Some changes were observed at the microscopic level, although no thickening of the endplate was apparent. The enzyme-linked immunosorbent assay analysis provided significant data for all three regions of the disc (nucleus, inner anulus, and outer anulus). When comparing the compressed disc (L3/L4) with either of the control discs (T13/L1 and L4/L5), in the compressed disc: 1) the nucleus contained less proteoglycan and more collagen I and II; 2) the inner anulus contained less proteoglycan and collagen I; and 3) the outer anulus contained more proteoglycan and less collagen I. The collagen II differences for the inner and outer anulus were not significant. CONCLUSION: Compression applied to the lumbar intervertebral discs of dogs for up to a year does not produce degeneration in any visible form. It does produce microscopic changes and numerical changes, however, in the amounts of proteoglycan and collagen in the nucleus, inner anulus, and outer anulus. The present results add no credence to the commonly held belief that high compressive forces play a causative role in disc degeneration.

Animals↗

Effects of chondroitinase ABC on degenerative intervertebral discs.

The effects of chondroitinase ABC on surgically induced degenerative rabbit intervertebral discs were determined during a 12-week period by magnetic resonance imaging, radiography, and histologic examination. Rabbit intervertebral discs were surgically extruded, inducing disc degeneration 12 weeks before injection of chondroitinase ABC. Magnetic resonance imaging showed a hypointense area in the center of the surgically induced disc degeneration. After injection of chondroitinase ABC, the hypointense area became more intense, but reversed somewhat by the end of the 12-week period. Additional evidence of the effects of chondroitinase ABC on a surgically induced degenerative disc model was shown by radiographic evidence of shrinkage of the disc after injection. Histologic examination revealed a fibrous degenerative disc induced by surgical extrusion. However, the staining properties of the matrix of the nucleus pulposus was similar to that of normal discs before chondroitinase ABC injection, but diminished after the injection, with slight recovery at 12 weeks. The results suggest that chondroitinase ABC induces chemonucleolysis in the degenerated disc. Also, chondroitinase ABC does not destroy the degenerative disc matrix ability to regenerate after 12 weeks.

Animals↗

Identification of human intervertebral disc stromelysin and its involvement in matrix degradation.

Human intervertebral disc when maintained in organ culture released a latent casein-degrading metalloproteinase into the medium in a manner analogous to cultures of human cartilage. This enzyme was demonstrated to be immunologically identical to prostromelysin. It was also found that the amount of procollagenase secreted by both cartilage and disc cells was considerably less than that of prostromelysin. Tissue extraction confirmed that the low level of procollagenase observed was not due to retention of the enzyme within the tissue. Human intervertebral disc link proteins were found to possess the same N-termini as those of their counterparts in human articular cartilage, where it appears that stromelysin is responsible for generating molecular heterogeneity. These results suggest that intervertebral disc cells are capable of secreting prostromelysin, which can become activated within the extracellular matrix and hence contribute to the age-related and degenerative changes in the disc.

Adult↗

Intervertebral disc infection after lumbar chemonucleolysis: report of a case.

Intervertebral disc space infection can be a serious and disabling complication of any procedure that affords entry for bacteria into the susceptible disc space. Most disc space infections occur after cervical or lumbar laminectomies. Discitis has been reported after myelography, lumbar puncture, paravertebral injection, and obstetrical epidural anesthesia. A case of septic discitis occurring after intradiscal therapy with chymopapain is presented. Patients who return for evaluation of recurrent spinal pain after chemonucleolysis, especially those with paravertebral muscle spasm, should be evaluated for the possibility of disc space infection by obtaining an erythrocyte sedimentation rate, peripheral white count, differential cell count, and plain roentgenograms. Radionuclide bone scans, although not specific, may provide further objective evidence leading to the diagnosis of an intervertebral disc space infection.

Blood Sedimentation↗

[A histopathological study on the intervertebral discs of idiopathic and paralytic scoliosis--abnormalities in transition from the notochordal nucleus to the fibrocartilaginous nucleus].

To elucidate morphologic events, 105 intervertebral discs in 22 patients with idiopathic scoliosis and 14 in four patients with paralytic scoliosis were histopathologically compared with 13 control intervertebral discs in 13 cases, including three fetuses. In control intervertebral discs, the notochordal area became smaller with age, and was almost completely occupied by fibrocartilagenous matrix at 16 years of age or more. In intervertebral discs of patients aged 19-33 with idiopathic scoliosis, many notochordal cells were seen and many areas without fibrocartilagenous matrix were found. In contrast, in intervertebral discs of patients aged 21-35 with paralytic scoliosis, there was no notochordal cells or defect of the fibrocartilagenous matrix. The results suggest an impairment of transition from the notochordal nucleus to the fibrocartilagenous nucleus in intervertebral discs in patients with idiopathic scoliosis, and that such abnormalities are related to the onset of idiopathic scoliosis.

Adolescent↗

Nitric oxide mediates the change of proteoglycan synthesis in the human lumbar intervertebral disc in response to hydrostatic pressure.

STUDY DESIGN: This in vitro study clarifies the role of nitric oxide (NO) in human lumbar intervertebral disc metabolism. OBJECTIVE: To investigate the effects of NO on proteoglycan synthesis in human lumbar discs and to test the hypothesis that NO is a mediator of the changes in proteoglycan synthesis in response to hydrostatic pressure. SUMMARY OF BACKGROUND DATA: The authors have clarified that hydrostatic pressure has an apparent effect on proteoglycan synthesis as well as matrix metalloproteinase production in the intervertebral disc. The cellular mechanisms underlying the response of disc cells to hydrostatic pressure remain to be clarified. Herniated lumbar discs produce NO in response to interleukin (IL)-1 beta. In articular cartilage, NO mediates the change of proteoglycan synthesis by IL-1 or shear stress. METHODS: Fifty-eight lumbar intervertebral disc specimens were obtained from patients who had undergone posterior discectomy. The specimens were chopped into 1-2-mm cubes and were incubated in a plastic syringe with 1 mL Dulbecco's modified Eagle's medium (DMEM). The syringes were placed in a water-filled pressure vessel kept at 37 C. Hydrostatic pressures of 1 (control), 3, and 30 atmospheres (atm) were applied. Proteoglycan synthesis was determined from (35)S-sulfate incorporation rates. Nitrite (the stable oxidation product of NO) concentration in DMEM was determined by a spectrophotometric method based on the Griess reaction. As a competitive inhibitor of NO synthases, N(G)-methyl-l-arginine (l-NMA, 10-1000 micromol) and as an organic donor of NO, S-nitroso-N-acetylpenicillamine (SNAP, 1-200 micromol) were used. RESULTS: Addition of l-NMA suppressed NO production and increased proteoglycan synthesis rates in the intervertebral disc specimens in a dose-dependent fashion. Addition of SNAP increased exogenous NO content in the medium significantly and suppressed proteoglycan synthesis rates in a dose-dependent fashion. Three-atmosphere hydrostatic pressure stimulated the proteoglycan synthesis rates. Rates were approximately 1.3-fold greater than at 1 atm, whereas 30-atm pressure inhibited proteoglycan synthesis rates. However, the hydrostaticpressure had inverse effect on NO production. At 3 atm, NO production decreased slightly relative to 1 atm, whereas at a pressure of 30 atm, NO production was increased and was approximately 1.32-fold greater than at 1 atm. L-NMA enhanced the 3-atm pressure-induced increase in proteoglycan synthesis and also relieved the suppression of proteoglycan synthesis at a pressure of 30 atm. CONCLUSION: The current study confirmed the previous finding that human herniated lumbar disc cultures spontaneously produce NO. Endogenously generated and exogenously supplied NO inhibited proteoglycan synthesis in the intervertebral disc. Hydrostatic pressure influenced NO production by disc cells, and NO is one of the mediators that changes proteoglycan synthesis in response to hydrostatic pressure. These results may show that autocrine and paracrine mechanisms of NO play an important role in the regulation of disc cell metabolism under mechanical stress and in the pathophysiology of intervertebral disc degeneration.

Adolescent↗

Proteoglycans and collagen in the intervertebral disc of the rhesus monkey (Macaca mulatta).

The different varieties of supportive tissues in the intervertebral discs of the rhesus monkeys (Macaca mulatta) were investigated with regard to morphology of the collagen fibrils and distribution and localization of proteoglycans (PG). The annulus fibrosus and the nucleus pulposus of the intervertebral disc were structurally closely integrated into the cartilaginous endplates of the vertebral bodies. The collagen fibrils in the intervertebral disc fell into two categories; i.e. thick (70-110 nm) and thin (40-50 nm) ones. In the outer zone of the annulus fibrosus only thick fibrils occurred, while in the regions of the inner part of the annulus fibrosus, in the periphery of the nucleus pulposus and in the cartilaginous endplates both types of fibrils were found. PG were found free in the matrix and in great numbers in association with collagen fibrils in all regions of the intervertebral disc. They interconnected neighbouring fibrils and decorated the surface of the collagen fibrils in irregular orientation. Only the thick fibrils of the annulus fibrosus contained small regularly arranged intrafibrillar PG precipitates. The free precipitates were usually longer and thicker than the collagen-associated PG, in addition they could be branched. Since rhesus monkeys are closely related to humans, they can serve as model organisms and the findings presented may be of relevance to the understanding of the human intervertebral discs.

Animals↗

An immunohistochemical study of nerve structures in the anulus fibrosus of human normal lumbar intervertebral discs.

STUDY DESIGN: The innervation of the anulus fibrosus of human macroscopically normal intervertebral discs from five patients was investigated immunohistochemically. OBJECTIVES: Immunoreactivity to general nerve markers (synaptophysin and protein gene product 9.5) and to neuropeptides (substance P and C-flanking peptide of neuropeptide Y) was studied. SUMMARY OF BACKGROUND DATA: In the lumbar disc of a newborn, free nerve endings have been demonstrated in the outer layers of anulus fibrosus. In degenerated and herniated discs, nerve structures have been shown to penetrate deeper into the anulus fibrosus. There are only a few studies on the innervation of normal adult intervertebral disc tissue. METHODS: Thin frozen sections of human normal lumbar intervertebral disc tissue were immunostained for general nerve markers and neuropeptides. RESULTS: Synaptophysin and protein gene product 9.5 immunoreactive nerve structures were observed penetrating 3.5 mm and 1.1 mm into the anulus, respectively. Immunoreactivity to C-flanking peptide of neuropeptide Y and substance P were observed at a maximum depth of 0.9 and 0.5 mm in the anulus, respectively. Antibodies to the former have been used to study sympathetic nerves, whereas substance P is a transmitter present in sensory nerves. CONCLUSIONS: In anulus fibrosus samples from macroscopically normal discs, a general marker for nerve endings can be found at a depth of a few millimeters, whereas neuropeptide markers show nerves only in the outermost layers of the anulus fibrosus. This absence of demonstrable nerves in deeper anulus fibrosus in normal discs is probably not a methodologic artifact, because blood vessels have also been demonstrated only at the disc surface. It is, however, possible that neuropeptide nerves also penetrate to a depth of a few millimeters, but that methodologic limitations permit the visualization of only the neuropeptide nerves closest to the disc surface. The results of the present study lend support to previous suggestions that, except at the surface, a normal intervertebral disc is almost without innervation.

Adolescent↗

Investigation of anulus fibrosus morphology in human fetus intervertebral discs.

OBJECTIVE: To determine whether the thickness of the anulus fibrosus (AF) structure of the intervertebral disc plays a role in disc herniation etiology, an important pathology. METHODS: We performed this study between February 2000 and May 2001 at Karadeniz Technical University Medical Faculty, Turkey. We used 20 human fetus cadavers with intrauterine ages between 22 and 41 weeks, taking into consideration the highest, lowest, and average frequencies, with 3 each of cervical, thoracal, and lumbar parts of the vertebral column, using a total of 9 intervertebral discs. We measured the thickness of the AF layer in each intervertebral disc in anterior, posterior, postero-dexter, and postero-sinister locations. We performed comparisons among the values obtained at the same level, and of comparative thicknesses at the same location at other levels. RESULTS: It was determined that there was no difference between the thickness of the AF in the same location at the various levels of intervertebral discs, but that at almost all levels, the thickness in posterior and anterior locations was significantly less compared to that in posterolateral locations. CONCLUSION: Anulus fibrosus thickness is not directly related to the incidence of disk hernia at different levels of the vertebral column according to the values obtained from this study.

Cadaver↗

Experimental study of temperature distributions and thermal transport during radiofrequency current therapy of the intervertebral disc.

STUDY DESIGN: The authors measured the temperature changes within the human intervertebral disc during transient intradisc heating with a radiofrequency current lesion generator. OBJECTIVES: The study was undertaken to evaluate the efficacy of thermal denervation of the intervertebral disc from intradisc radiofrequency lesion treatment. SUMMARY OF BACKGROUND DATA: Intradisc radiofrequency heating has emerged recently as a nonoperative treatment for chronic lower back pain. However, no literature exists regarding the temperature distributions within the disc and the consequent efficacy of denervation. METHODS: Vertebral segments obtained at autopsy were instrumented with thermocouples, and intradisc heating was performed according to standard clinical protocols. The tip was maintained at 70 C and the temperature monitored at various distances from the tip. RESULTS: The temperature changes at distances further than 11 mm were insufficient to raise the tissue temperature to the 42 C needed for neuronal cell death. Using the thermal transient data, the authors calculated the thermal diffusivity of the human intervertebral disc and found it to vary from approximately 1.7 x 10(-7) +/- 0.4 x 10(-7) m2/sec in the disc from a 61-year-old man to approximately 4.5 x 10(-7) +/- 1.4 x 10(-7) m2/sec in the disc from a 32-year-old man. CONCLUSIONS: The authors concluded that the mechanism of observed clinical improvement from radiofrequency heating of intervertebral discs is not thermal denervation of the disc and that the physicochemical state of the disc is important to consider when designing a therapeutic heating protocol if thermal denervation is clinically desired.

Adult↗

Residual chymopapain activity after chemonucleolysis in normal intervertebral discs in dogs.

Studies were carried out to demonstrate residual chymopapain activity in intervertebral discs after chemonucleolysis; protease assay, enzyme-linked immunosorbent assay, and immunohistochemical localization of the chymopapain in the disc tissue were done. Chymopapain, one milligram per level, was injected into the normal lumbar intervertebral discs of adult mongrel dogs and the discs were excised after two weeks. Proteolytically active chymopapain was still present in the extract of intervertebral disc at this time. The proteolytic activity was decreased by sulfhydryl inhibitors but not by inhibitors of metalloproteases or serine proteases. Protease and enzyme-linked immunosorbent assays showed that 0.60 +/- 0.48 per cent and 0.49 +/- 0.38 per cent of the original dose was present two weeks after the injection. Chymopapain was shown by immunohistochemical staining to be diffusely located throughout the extracellular matrix of the anulus fibrosus and the nucleus pulposus. Some cells, located mainly in the inner portion of the anulus, contained vacuoles filled with immunoreactive product.

Animals↗

Neovascularization of nucleus pulposus. A diagnostic feature of intervertebral disc prolapse.

STUDY DESIGN: Seventy-five surgically excised prolapsed intervertebral discs were histopathologically evaluated. Fifteen prospective normal cadaveric discs were used as control specimens. OBJECTIVE: To compare the morphologic features between the prolapsed and normal discs. SUMMARY OF BACKGROUND DATA: The histologic criteria were edge neovascularization of the fibrocartilage, chondrocyte cloning, fibrillation with fraying, and granular change. METHODS: Sections stained with hematoxylin and eosin, Van Gieson's, and toluidine blue were studied. The presence or absence of edge neovascularization was noted. The other criteria were graded based on a semiquantitative scoring system. RESULTS: Edge neovascularization was observed in 56% of the discs in the test group and in none of the control specimens. Fibrillation with fraying was the most significant finding in the test group (P < 0.001). Although the mean grades were higher in the test group, they did not predict the presence of edge neovascularization. CONCLUSIONS: Edge neovascularization was the most significant finding to confirm disc prolapse. Fibrillation with fraying, was observed more frequently in prolapsed intervertebral discs and the grades of fibrillation with fraying, chondrocyte cloning, and granular change were significantly higher in the test group. Pathologists can usually agree on the presence or absence of a particular histologic characteristic but are rarely consistent when they estimate the degree. Simple, reproducible agreed-on criteria are needed before semiquantitative evaluations become reliable.

Adolescent↗

Lumbar intervertebral disc cyst as a cause of radiculopathy.

BACKGROUND CONTEXT: Lumbar radiculopathy is commonly caused by degenerative conditions such as a herniated disc or lumbar spinal stenosis. Less common etiologies include intraspinal extradural masses such as synovial cysts and gas-containing ganglion cysts. Intraspinal extradural cysts that communicate with the intervertebral disc are a rare entity and thus, an uncommon cause of lumbar radiculopathy. There are only ten cases of an intervertebral disc cyst reported in the literature. PURPOSE: To document the first reported case of an intervertebral disc cyst in North America. Two series of Japanese patients with intervertebral disc cyst confirmed radiographically and intraoperatively have recently been reported. STUDY DESIGN: A case report of an intervertebral disc cyst at L4-5 causing an L5 radiculopathy. OUTCOME MEASURES: Japanese Orthopaedic Association score for low back pain. METHODS: The patient and the authors involved in the patient's management were interviewed. All medical records, radiographic imaging studies, intraoperative findings, and pertinent literature were also reviewed. RESULTS: Preoperative magnetic resonance imaging (MRI) scan demonstrated a well-localized cyst compressing the ventral aspect of the thecal sac at L4-L5. Discography and subsequent computed tomographic (CT) scanning demonstrated the cyst communicating with an intervertebral disc herniation via an annular rupture. Decompressive discectomy and surgical excision of the disc cyst from the spinal canal resulted in complete recovery and resolution of the preoperative radiculopathy. Clinical improvement was documented using the JOA scoring system. Patient's preoperative score was 4/15, and postoperative score was 15/15. CONCLUSION: Although exceedingly rare, an intervertebral disc cyst should remain in the differential diagnosis of any extradural intraspinal mass ventral to the thecal sac. Diagnosis of an intervertebral disc cyst requires recognition of this uncommon entity and a high index of suspicion. Discography and post-discography computerized tomography (CT) scan confirm the diagnosis. Operative treatment includes decompression, and excision of the cyst and is reserved only for cases in which the cyst results in clinical symptoms unresponsive to nonoperative management.

Adult↗

The ligaments and annulus fibrosus of human adult cervical intervertebral discs.

STUDY DESIGN: Descriptive, microdissection study. OBJECTIVE: To determine the morphology of the human adult cervical intervertebral disc and its ligaments. SUMMARY OF BACKGROUND DATA: Some studies indicate that the cervical disc is distinctly different from the lumbar intervertebral disc, yet most clinical and anatomic texts appear content with extrapolating data from the lumbar spine. A detailed three-dimensional description of the cervical intervertebral disc and its surrounding ligaments is currently unavailable. METHODS: Whole cervical spinal columns were freed from 12 human adult embalmed cadavers, and the posterior elements and soft tissues were removed. Using microdissection, the longitudinal ligaments and the fibrous components of 59 cervical intervertebral disc were resected systematically. The orientation, location, and attachments of each stripped bundle of collagen were recorded photographically and in sketches. RESULTS: The cervical anulus fibrosus does not consist of concentric laminae of collagen fibers as in lumbar discs. Instead, it forms a crescentic mass of collagen thick anteriorly and tapering laterally toward the uncinate processes. It is essentially deficient posterolaterally and is represented posteriorly only by a thin layer of paramedian, vertically orientated fibers. The anterior longitudinal ligament covers the front of the disc, and the posterior longitudinal ligament reinforces the deficient posterior anulus fibrosus with longitudinal and alar fibers. CONCLUSIONS: The three-dimensional architecture of the cervical anulus fibrosus is more like a crescentic anterior interosseous ligament than a ring of fibers surrounding the nucleus pulposus.

Adult↗

Gene therapy approaches for intervertebral disc degeneration.

STUDY DESIGN: Review of the literature concerning the development of gene therapy approaches for the treatment of intervertebral disc degeneration. OBJECTIVES: To provide an overview of gene therapy principles, summarize the results of completed gene therapy studies, and discuss considerations for the direction of future research. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration is characterized by progressive loss of the proteoglycan matrix in the nucleus pulposus. Exogenous growth factors have been shown to transiently increase matrix synthesis. Gene therapy offers exciting potential to induce and sustain endogenous production of growth factors within the intervertebral disc and thus possibly alter the degenerative course. METHODS: Published and presented scientific literature was examined. RESULTS/CONCLUSIONS: Several in vitro and in vivo studies have documented the capacity of gene therapy to favorably modify the biologic functions of intervertebral disc cells with the delivery of the cDNA for various growth factors. Currently, investigators are exploring the efficacy and safety of gene therapy in animal models of degeneration. With promising initial results and an immense potential clinical impact, gene therapy approaches for treatment of intervertebral disc degeneration will continue to receive dedicated research efforts.

Animals↗