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PubMed2006

Biologic modification of animal models of intervertebral disc degeneration.

Intervertebral disc degeneration is a chronic process that can become manifest in clinical disorders such as idiopathic low back pain, sciatica, disc herniation, spinal stenosis, and myelopathy. The limited available treatment options (including discectomy and spinal fusion) for these and other disabling conditions that arise from intervertebral disc degeneration are highly invasive, achieve limited success, and only address acute symptoms while doing nothing to halt the process of degeneration. Although the precise pathophysiology of intervertebral disc degeneration has yet to be clearly delineated, the progressive decline in aggrecan, the primary proteoglycan of the nucleus pulposus, appears to be a final common pathway. Animal models as well as in vitro studies of the process of disc degeneration have yielded many potentially useful targets for the reversal of disc degeneration. One current research trend is the use of established animal models of disc degeneration to study the role of therapeutic modalities in reversing the process of degeneration, often with use of the delivery of genes or gene products that influence the anabolic and catabolic pathways of the disc. This article reviews the ability of gene-product delivery systems and gene therapy to alter biologic processes in animal models of disc degeneration and examines future trends in this field.

Animals↗
PubMed2006

Programmed cell death in intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration is largely a process of destruction and failure of the extracellular matrix (ECM), and symptomatic IVD degeneration is thought to be one of the leading causes of morbidity or life quality deterioration in the elderly. To date, however, the mechanism of IVD degeneration is still not fully understood. Cellular loss from cell death in the process of IVD degeneration has long been confirmed and considered to contribute to ECM degradation, but the causes and the manners of IVD cell death remain unclear. Programmed cell death (PCD) is executed by an active cellular process and is extensively involved in many physiological and pathological processes, including embryonic development and human degenerative diseases. Thus, the relationship between PCD and IVD degeneration has become a new research focus of interest in recent years. By reviewing the available literature concentrated on PCD in IVD and discussing the methodology of detecting PCD in IVD cells, its inducing factors, the relationship of cell death to ECM degradation, and the potential therapy for IVD degeneration by modulation of PCD, we conclude that IVD cells undergo PCD via different signal transduction pathways in response to different stimuli, that PCD may play a role in the process of IVD degeneration, and that modulation of PCD might be a potential therapeutic strategy for IVD degeneration.

Animals↗
PubMed2003

Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration.

Intervertebral disc degeneration is considered to be one of the major causes of low back pain. Despite this irreversible phenomenon, attempts to decelerate disc degeneration using various techniques have been reported. However, to date there has been no proven technique effective for broad clinical application. Based on previous studies, we hypothesize that maintenance of proteoglycan content in the disc is achieved by avoiding the depletion of nucleus pulposus and preserving the structure of the annulus is a primary factor in decelerating disc degeneration. One novel approach to solve the dilemma of intervertebral disc degeneration is found at the stem cell level. Mesenchymal stem cells (MSCs) are known to possess the ability to differentiate into various kinds of cells from mesenchymal origin. Although the majority of cells that contribute to disc formation are known to obtain chondrocyte-like phenotypes, no reported study has emphasized the correlation with mesenchymal stem cells. To evaluate the possible potential of MSCs in disc cell research and treatment of degenerative disc disease, autologous MSCs embedded in Atelocollagen gel were transplanted into the discs of rabbits which had undergone a procedure proven to induce degeneration. The results suggest that MSC transplantation is effective in decelerating disc degeneration in experimental models and provided new hopes for treatment of degenerative disc disease in humans. Atelocollagen gel served as an important carrier of MSCs in transplantation, permitting proliferation, matrix synthesis and differentiation of MSCs. This study strengthens the viable efficacy of practical application of MSCs in treatment of intervertebral disc disease.

Animals↗
PubMed2003

Gene therapy applications for intervertebral disc degeneration.

STUDY DESIGN: Review of current approaches to gene therapy as a potential treatment modality for regeneration of the degenerating intervertebral disc. OBJECTIVES: Describe recent advances in the field of gene therapy pertaining to treatment of the degenerating intervertebral disc. SUMMARY OF BACKGROUND DATA: The potential application of gene therapy to the treatment of degenerative disc disease has been an area of exciting and active research. Several in vitro studies have documented the capacity of gene therapy to favorably modify the biologic functions of the intervertebral disc cells with the delivery of the cDNA for various growth factors, whereas in vivo studies have reinforced this potential in animal models. Currently, investigators are exploring the therapeutic potential of gene delivery of the cDNA for several promising factors. METHODS: Literature review. RESULTS/CONCLUSIONS: The application of gene therapy to the treatment of the degenerating intervertebral disc holds much clinical promise and continues to expand as an area of active research. The therapeutic potential of multiple agents, as well as possible vectors, are currently being investigated with encouraging results.

Animals↗
PubMed1981

Biochemical changes in intervertebral disc degeneration.

The distribution of the principal matrix components, collagen, proteoglycans and water, across the diameter of human normal and degenerate intervertebral discs was compared. Little difference in collagen distribution was noted between normal and degenerate tissue but water and proteoglycan content decreased with degeneration, particularly in the centre of the disc. Proteoglycans of the nucleus pulposus and annulus fibrosus of normal and degenerate intervertebral discs were examined. In comparison with monomers of normal tissues, degenerate disc proteoglycans were of larger average hydrodynamic size and had a higher glucosamine to galactosamine ratio. Proteoglycans were digested with chondroitinase ABC and passed over an HS-Sepharose 2B affinity column. A greater proportion of the keratan sulphate-protein cores from degenerate disc were capable of interaction with the immobilized hyaluronate. Loss of aggregating ability was associated with diminution in size of the core. It is suggested that a large proportion of proteoglycans from normal disc have undergone a degree of degradation in the hyaluronate binding region and that proteoglycan synthesis in this tissue is slower than in degenerate tissue.

Adult↗
PubMed1998

Correlation between bone mineral density and intervertebral disc degeneration.

STUDY DESIGN: Intervertebral disc area, disc bulge ratio, and bone mineral density were measured in 86 postmenopausal women and the data analyzed. OBJECTIVE: To examine quantitatively the correlation between intervertebral disc degeneration and bone mass. SUMMARY OF BACKGROUND DATA: In results of previous studies, an inverse correlation between osteoporosis and spondylosis has been reported. In these studies, only radiographic findings were used to evaluate spondylosis; changes in the intervertebral disc itself were not investigated. METHODS: To determine bone mass, total-body bone mineral density, lumbar bone mineral density, and age-matched control values of bone mineral density were measured by dual-energy X-ray absorptiometry in all cases. To evaluate intervertebral disc degeneration, disc area and disc bulge ratio (calculated by measuring the areas protruding from lines connecting the middle points of the anterior and posterior borders of the vertebral bodies) were obtained from four discs, using magnetic resonance images of the lumbar spine. The correlation between bone mass data and disc area data was analyzed. RESULTS: Bone mineral density showed a significant decrease with increasing age. Disc area and disc bulge ratio had no relation to age. There was a negative correlation between total-body bone mineral density, lumbar bone mineral density, and age-matched control values versus disc area, and a positive correlation between all bone mineral density data and the disc bulge ratio. CONCLUSIONS: According to the results of the analysis by disc morphology and bone mass, especially total body bone mineral density, bone mass has an inverse correlation to intervertebral disc degeneration--i.e., reduction and disc bulge--which is important when considering degenerative spinal diseases and osteoporosis.

Absorptiometry, Photon↗
PubMed2005

2004 Young Investigator Award Winner: vertebral endplate marrow contact channel occlusions and intervertebral disc degeneration.

STUDY DESIGN: Intervertebral disc degeneration was evaluated by morphologic appearance, magnetic resonance imaging, and by biochemical matrix composition. Caliber and distribution of openings of the adjacent vertebral osseous endplates were measured. OBJECTIVES: Correlation between occlusion of vertebral endplate openings and intervertebral disc degeneration was quantified. SUMMARY OF BACKGROUND DATA: Calcifications of vertebral endplates with disease and age have suggested insufficient nutrition as a mechanism for intervertebral disc degeneration. It has been proposed that occlusion of endplate openings, which contain vascular sources for the disc, may limit the transport of nutrients, leading to disc degeneration. METHODS: Fresh magnetic resonance images from 39 human lumbar discs were scored. Sectioned discs with endplates were morphologically graded. Samples of nuclear and anular regions were evaluated for proteoglycan and collagen contents. Backlight microscopic images of 4 endplate regions were obtained, and caliber and distribution of endplate openings for each disc were measured. Analysis of variance regression models were used to assess correlation between endplate openings and disc degeneration. RESULTS: The decrease in opening density significantly correlated to morphologic degeneration grade, best for openings with 20 to 50 im equivalent diameter and in the nuclear region. Although the density of 20 to 50 im openings also significantly indirectly correlated to age, it was not as strong as the correlation to degeneration grade. Opening density was also significantly correlated to proteoglycan content in all regions. However, all other biochemical parameters as well as the T2 intensity score showed only weak or no correlation to opening density. CONCLUSIONS: A high indirect correlation between the density of openings in the osseous endplate (particularly of the size of the capillary buds) and the morphologic degeneration grade of the disc support the hypothesis that occlusion of these openings may deprive the cells of nutrients, leading to insufficient maintenance of the extracellular matrix and disc degeneration.

Adult↗
PubMed1997

Matrix metalloproteinase-3 production by human degenerated intervertebral disc.

To assess its possible role in the pathophysiology of intervertebral disc degeneration, we investigated the production of matrix metalloproteinase-3 (MMP-3) using human intervertebral disc explant culture. Five normal and 10 degenerated disc specimens were used. The levels of MMP-3 released in the medium were measured with use of an enzyme immunoassay. The results showed that the level of MMP-3 in the degenerated group (0.57 microg/ml/mg wet weight; n = 10) was significantly higher than that of the control group (0.29 microg/ml/mg wet weight; n = 5) (p < 0.05). Immunostaining of MMP-3 revealed that the ratio of positive staining cells in the degenerated group was greater than that of the control group. These observations suggest that MMP-3 produced by human intervertebral disc may be involved in the intervertebral disc degeneration, particularly in the initiation of matrix degradation of intervertebral disc.

Adult↗
PubMed2005

Effects of controlled dynamic disc distraction on degenerated intervertebral discs: an in vivo study on the rabbit lumbar spine model.

STUDY DESIGN: An in vivo study on the rabbit lumbar spine model. OBJECTIVES: Effects of temporary dynamic distraction on intervertebral discs were studied on the lumbar spine rabbit model to characterize the changes associated with disc distraction and to evaluate feasibility of temporary disc distraction to previously compressed discs in order 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 are needed. METHODS: New Zealand white rabbits (n = 32) were used for this study. The rabbits were randomly assigned to one of five groups. In 12 animals, the discs were first loaded for 28 days using a custom-made external loading device to stimulate disc degeneration. After 28 days loading time, the discs in six animals were distracted for 7 days and in six animals for 28 days using the same external device, however, modified as dynamic distraction device. In six animals, the discs were distracted for 28 days without previous loading; and in six animals, the discs were loaded for 28 days and afterwards the loading device removed for 28 days for recovery without distraction. Six animals were sham operated. The external device was situated; however, the discs remained undistracted and they also served as controls. After 28 to 56 days loading and distraction time, the animals were killed and the lumbar spine was harvested for examination. Disc height, disc morphology, cell viability, relative neutral zone, and tangent modulus were measured. RESULTS: After 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 reversible after 28 days of distraction. The disc thickness increased significantly as compared with the specimens from the 28 days loading group without distraction. Histologically, the discs showed signs of tissue regeneration after 28 days of distraction. The number of dead cells decreased significantly in comparison with the loaded discs without distraction. The flexibility of compressed discs was higher than of compressed/distracted discs. CONCLUSIONS: The results of this study suggest that disc regeneration can be induced by axial dynamic distraction in the rabbit intervertebral disc. The decompressed rabbit intervertebral discs showed signs of tissue recovery on a biologic, cellular, and a biomechanical level after 28 days of distraction.

Animals↗
PubMed2006

Relevance of in vitro and in vivo models for intervertebral disc degeneration.

Models available for the study of intervertebral disc degeneration are designed to answer many important questions. In vitro biologic models employ a variety of cell, tissue, or organ culture techniques with culture conditions that partially mimic the cellular environment of the degenerated human intervertebral disc. In vitro biomechanical models include intervertebral disc or motion-segment loading experiments as well as finite element modeling techniques. The literature describes numerous in vivo animal models for use in the study of intervertebral disc degeneration, each of which has its own advantages and disadvantages. Human-subject studies have included the use of magnetic resonance imaging and other techniques to assess diffusion into the intervertebral disc, to measure intradiscal pressure, to conduct kinematic or stiffness studies of lumbar motion segments, and to evaluate muscular forces on the spine. Although all of these studies are helpful in answering specific questions, their relevance in assessing disc degeneration in patients with symptoms of discogenic pain must be carefully considered.

Age Factors↗
PubMed2004

[Pathological development of researches on intervertebral disc degeneration].

This article reviews the literature about the etiology and pathology of intervertebral disc degeneration. The degeneration of intervertebral disc is associated with certain biomechanical factor. Stress can directly lead to the rupture of intervertebral disc and, more importantly, change its biological properties. And then, it can trigger the process of degeneration via inflammatory mechanism which may include autoimmunity.

Biomechanical Phenomena↗
PubMed2005

A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology.

STUDY DESIGN: The progression of intervertebral disc degeneration following anterolateral "stab" of adult rabbit lumbar discs by 16-gauge hypodermic needle to a limited (5-mm) depth was studied for up to 24 weeks using magnetic resonance imaging, radiograph, and histologic outcome measures. OBJECTIVES: To develop a slowly progressive, reproducible rabbit model of intervertebral disc degeneration suitable for studying pathogenesis and pathophysiology of intervertebral disc degeneration and testing safety and efficacy of novel approaches to the treatment of intervertebral disc degeneration (e.g., growth factors, gene therapy, cell therapy, and tissue engineering). SUMMARY OF BACKGROUND DATA: Numerous animal models of intervertebral disc degeneration have been proposed in the literature, each with attendant advantages and disadvantages. The classic "stab model," involving full-thickness stab of anterior anulus fibrosus of adult rabbit lumbar discs by a number 11 scalpel blade, appears to produce changes in certain biochemical and histologic outcome measures that are similar to changes seen in human intervertebral disc degeneration. However, the immediate herniation of nucleus pulposus on full-thickness stab renders this model less suitable for 1) studying effects of less precipitous changes in nucleus pulposus and anulus fibrosus that may be important in the onset and progression of intervertebral disc degeneration and 2) testing novel therapeutic approaches that target the processes of early intervertebral disc degeneration. METHODS: The L2-L3, L3-L4, and L4-L5 lumbar intervertebral discs of 18 skeletally mature female New Zealand White rabbits were stabbed by 16-gauge hypodermic needle to a depth of 5 mm in the left anterolateral anulus fibrosus. Serial magnetic resonance imaging scans of the stabbed discs and intact L1-L2 and L5-L6 control discs were performed at 3, 6, 12, and 24 weeks post surgery and compared with preoperative magnetic resonance images. Supplemental radiograph and histologic analyses were performed. RESULTS: The stabbed discs exhibited a progressive decrease in "magnetic resonance imaging index" (the product of nucleus pulposus area and signal intensity from T2-weighted midsagittal plane images) starting at 3 weeks post stab and continuing through 24 weeks, with no evidence of spontaneous recovery or reversal of magnetic resonance imaging changes. Radiograph findings included early osteophyte formation by 6 weeks post stab and extensive, bridging osteophytes by 24 weeks. Histologic analysis revealed progressive loss of notochordal cells from the nucleus pulposus, filling of the nucleus pulposus space with fibrocartilage, and derangement of anulus fibrosus. CONCLUSIONS: Stabbing the anterolateral anulus fibrosus of adult rabbit lumbar discs with a 16-gauge hypodermic needle to a limited (5-mm) depth results in a number of slowly progressive and reproducible magnetic resonance imaging, radiograph, and histologic changes over 24 weeks that show a similarity to changes seen in human intervertebral disc degeneration. This model would appear suitable for studying pathogenesis and pathophysiology of intervertebral disc degeneration and testing safety and efficacy of novel treatments of intervertebral disc degeneration.

Animals↗
PubMedDate not supplied

1980 Volvo award in basic science. Proteoglycans in experimental intervertebral disc degeneration.

An animal model of intervertebral disc degeneration induced surgically by ventral nuclear herniation in the rabbit produces morphologic changes of disc degeneration. Histologic characteristics and proteoglycan changes have been studied at various times after herniation. After injury, there was metaplasia into fibrocartilage originating from the cells along the margins of the annular wound, with proliferation of cells changing almost the entire disc space into fibrocartilage. A vertebral osteophyte occurred through an endochondral ossification sequence. Aggregating proteoglycans had two periods of repletion in the early course of degeneration. The water content of the disc was rapidly but only transiently restored in the first two days after herniation, whilst the changes in the total proteoglycan content of the disc paralleled these changes. Hyaluronic acid content decreased rapidly after herniation, but the size of the proteoglycan monomers did not change with degeneration. It is suggested that loss of confined fluid mechanics signals an abortive repair attempt rather than that of biochemical changes in proteoglycans initiate disc degeneration.

Animals↗
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↗
PubMed1998

Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration.

STUDY DESIGN: A study in genetic epidemiology of disc degeneration, based on lifetime exposure data, findings on magnetic resonance imaging, and genotyping of intragenic markers. OBJECTIVES: To pursue the potential correlation between common allelic variations in the vitamin D receptor locus and degeneration of the intervertebral disc. SUMMARY OF BACKGROUND DATA: Familial aggregation has been observed in intervertebral disc degeneration, but the relative significance of the genetic component and shared environmental influences is unknown. The identification of relevant candidate genes associated with disc degeneration would specify a genetic component and increase our understanding of the etiopathogenesis of disc degeneration. METHODS: From the population-based Finnish Twin cohort, 85 pairs of male monozygotic twins were selected based on exposure to suspected risk factors for disc degeneration. Interview data were gathered on relevant lifetime exposures, and thoracic and lumbar disc degeneration was determined through quantitative and qualitative assessments of signal intensity on magnetic resonance imaging, and qualitative assessments of disc bulging and disc height narrowing. Possible associations were examined between disc degeneration measures and two polymorphisms of the coding region of the vitamin D receptor locus. RESULTS: Two intragenic polymorphisms of the vitamin D receptor gene revealed an association with disc degeneration. Quantitatively assessed signal intensities of thoracic and lumbar (T6-S1) discs were 12.9% worse in men with the Taql tt genotype and 4.5% worse in men with the Tt genotype, compared with signal intensity in men with the TT genotype (age adjusted P = 0.003). A similar pattern was found between disc signal intensity and Fokl genotypes; men with the ff and Ff genotypes had mean signal intensities that were 9.3% and 4.3% lower, respectively, than those in men with FF genotypes (age-adjusted P = 0.006). The summary scores of qualitatively assessed signal intensity, bulging, and disc height were 4.0% and 6.9% worse in men with Ff and ff genotypes, respectively, when compared with those in men with the FF genotype (age-adjusted P = 0.029). CONCLUSION: Specific vitamin D receptor alleles were associated with intervertebral disc degeneration as measured by T2-weighted signal intensity, demonstrating for the first time, the existence of genetic susceptibility to this progressive, age-related degenerative process.

Adult↗
PubMed2006

Possible pathogenesis of painful intervertebral disc degeneration.

STUDY DESIGN: We collected the specimens of lumbar intervertebral disc (i.e., the symptomatic degenerative disc) from patients with discogenic low back pain to study the histopathologic features and growth factor expressions. OBJECTIVES: To study the pathogenesis of disc degeneration, meanwhile discriminating between common disc degeneration (aging disc) (i.e., black asymptomatic disc, not clinically relevant) and painful disc degeneration (i.e., symptomatic disc, clinically relevant). SUMMARY OF BACKGROUND DATA: The pathogenesis of intervertebral disc degeneration is poorly understood, mainly because of the difficulty to establish the experimental model with good reproducibility. Recently, the popularity of spinal fusion leads to more opportunities to obtain disc specimens, which could be applied to explore the pathogenesis of disc degeneration with modern biologic techniques. METHODS: There were 21 specimens of lumbar intervertebral discs from 15 patients with discogenic low back pain during posterior lumbar interbody fusion, 16 aging discs from patients without low back pain, and 10 normal discs as control collected for the study of their histopathologic features, as well as the expressions of basic fibroblast growth factor (bFGF) and its receptor (Flg), transforming growth factor-beta1 (TGF-beta1) and its receptor (TGF-betaRI) by immunohistochemistry. The distribution of macrophages and mast cells was also noted. Proliferating cell nuclear antigen was assessed to evaluate proliferating activities of disc cells. RESULTS: The distinct histologic characteristic of the disc from the patient with discogenic low back pain was the ingrowth of vascularized granulation tissue along torn fissures, extending from the external layer of the anulus fibrosus into the nucleus pulposus. The immunohistochemical staining showed that there were strong expressions of bFGF and TGF-beta1 and their receptors, as well as a strong expression of proliferating cell nuclear antigen in the zones of granulation tissue in the painful discs. However, there were only weak expressions in the nongranulation tissue zones in the painful discs and aging discs, and no expression in the control discs. In addition, abundant macrophages and mast cells were found in the granulation tissue zones of painful discs but absent in the nongranulation tissue zones of painful discs or aging discs and the normal control discs. CONCLUSIONS: The findings indicated that degeneration of the painful disc might originate from the injury and subsequent repair of anulus fibrosus. Growth factors, such as bFGF and TGF-beta1, macrophages and mast cells might play a key role in the repair of the injured anulus fibrosus and subsequent disc degeneration.

Adult↗
PubMed2002

Mechanism of intervertebral disc degeneration caused by nicotine in rabbits to explicate intervertebral disc disorders caused by smoking.

STUDY DESIGN: The effects of nicotine on intervertebral discs in rabbits were studied experimentally. OBJECTIVES: To investigate the effects of nicotine on the vascular buds in rabbits for elucidating the mechanism of nicotine-induced vertebral disc degeneration. BACKGROUND DATA: Several groups have suggested that cigarette smoking is associated with low back pain, but the exact mechanism is not yet fully understood. METHODS: The pump was filled with a diluted nicotine solution, then implanted under the skin of rabbits for 8 weeks. This model was designed to maintain blood nicotine concentration at approximately 110 ng/mL. Rabbits receiving physiologic saline were used as control animals. RESULTS: Nicotine treatment resulted in necrosis and hyalinization of the nucleus pulposus in all rabbits. The anulus fibrosus showed a disturbance of the pattern of overlapping laminae with and without clefts and separation. These resulted in changes indicative of stenosis of vascular buds and perivascular calcification. Nicotine treatment resulted in hypertrophy of vascular walls, necrotic changes in endothelial cells, and narrowing of the vascular lumen. Nicotine treatment resulted in delineation of vascular buds in the vicinity of the vertebral endplate and a reduction of their numbers. However, the control animals showed a dense vascular network. The number of vascular buds decreased in nicotine treatment. CONCLUSION: The authors believe that both reduction in the density of vascular buds and narrowing of the vascular lumen result in decreased oxygen tension, leading to decreased synthesis of proteoglycan and collagen, thus facilitating degeneration of the disc.

Animals↗