Article

Spinal Traction Promotes Molecular Transportation in a Simulated Degenerative Intervertebral Disc Model

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Abstract

Study design: Biomechanical experiment using an in situ porcine model. Objective: To find the effect of traction treatment on annulus microstructure, molecular convection, and cell viability of degraded discs. Summary of background data: Spinal traction is a conservative treatment for disc disorders. The recognized biomechanical benefits include disc height recovery, foramen enlargement, and intradiscal pressure reduction. However, the influence of traction treatment on annulus microstructure, molecular transportation, and cell viability of degraded discs has not been fully investigated. Methods: A total of 48 thoracic discs were dissected from 8 porcine spines (140 kg, 6-month old) within 4 hours after killing them and then divided into 3 groups: intact, degraded without traction, and degraded with traction. Each disc was incubated in a whole-organ culture system and subjected to diurnal loadings for 7 days. Except for the intact group, discs were degraded with 0.5 mL of trypsin on day 1 and a 5-hour fatigue loading on day 2. From day 4 to day 6, half of the degraded discs received a 30-minute traction treatment per day (traction force: 20 kg; loading: unloading = 30 s: 10 s). By the end of the incubation, the discs were inspected for disc height loss, annulus microstructure, molecular (fluorescein sodium) intensity, and cell viability. Results: Collagen fibers were crimped and delaminated, whereas the pores were occluded in the annulus fibrosus of the degraded discs. Molecular transportation and cell viability of the discs decreased after matrix degradation. With traction treatment, straightened collagen fibers increased within the degraded annulus fibrosus, and the annulus pores were less occluded. Both molecular transportation and cell viability increased, but not to the intact level. Conclusion: Traction treatment is effective in enhancing nutrition supply and promoting disc cell proliferation of the degraded discs. Level of evidence: N/A.

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... Three studies (Colachis and Strohm, 1969;Kuo et al., 2014;Lai and Chow, 2010) investigated the effects of 30-minute intermittent traction on disc height, two of them (Kuo et al., 2014;Lai and Chow, 2010) used animal models in vivo and in vitro, and both of them also assessed disc morphology. One in vivo animal study (Lai and Chow, 2010) and two studies using human subjects (Janke et al., 1997;Tekeoglu, Adak, Bozkurt, and Gurbuzoglu, 1998) , and Liuzzo, 2014;Beattie, Donley, Arnot, and Miller, 2009;Beattie et al., 2010) investigated the effects of lumbar spine manual therapy on changes in water diffusion within the IVD (Table 1). ...
... Three studies (Colachis and Strohm, 1969;Kuo et al., 2014;Lai and Chow, 2010) investigated the effects of 30-minute intermittent traction on disc height, two of them (Kuo et al., 2014;Lai and Chow, 2010) used animal models in vivo and in vitro, and both of them also assessed disc morphology. One in vivo animal study (Lai and Chow, 2010) and two studies using human subjects (Janke et al., 1997;Tekeoglu, Adak, Bozkurt, and Gurbuzoglu, 1998) , and Liuzzo, 2014;Beattie, Donley, Arnot, and Miller, 2009;Beattie et al., 2010) investigated the effects of lumbar spine manual therapy on changes in water diffusion within the IVD (Table 1). ...
... These results suggest that increases in disc height over a three-week period are primarily dependent on the amount of traction load that is placed on a vertebral segment and that higher loads may preclude the imbibition of water for the recovery of disc height. Kuo et al. (2014) used in vitro porcine thoracic IVDs to study the effects of intermittent traction on disc height and the discs' molecular transportation capacity. After dissection, the discs were either left intact or were degraded with fatigue loading. ...
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Background context: The use of physical therapy has been recommended in the treatment of low back pain based on primarily mechanical and neurophysiological effects. Recent studies have measured the physiological effects of physical therapy interventions, including manual therapy and traction, on the intervertebral discs (IVD), and these findings may have implications for the long-term management or even prevention of low back pain. Purpose: The objective of this systematic review is to investigate the literature regarding possible physiological effects of physical therapy interventions on the intervertebral disc (IVD). Study design: Systematic Review. Methods: A literature search of published articles through December 2014 resulted in the retrieval of 8 clinical studies assessing the influence of physical therapy interventions on the physiology of the IVD. Results: Three studies, including two using animal models, investigated the effects of 30-minute intermittent traction on disc height. One in vivo animal study and two studies using human subjects assessed changes of disc height associated with static traction. Three studies investigated the effects of lumbar spine manipulation and mobilization on changes in water diffusion within the IVD. All studies confirmed, either directly or indirectly, that their respective intervention influenced disc physiology primarily through water flow. Conclusion: Physical therapy interventions may have an effect on the physiology of the IVD, primarily through water diffusion and molecular transport, which are important for the health of the IVD.
... Considering the deleterious effect of sustained compression from upright postures it has been hypothesized that a key effect of lumbar traction is to reduce external compression and thus favorably influence fluid movement within the IVD (Adams et al., 2010;Beattie, 2011). Studies using animal tissues ex vivo have supported this hypothesis (Lai and Chow, 2010;Kuo et al., 2014). For example, Kuo et al. (2014) recently reported that a 30-minute treatment of traction applied to degraded porcine IVDs was effective in enhancing their nutritional supply and promoting cell proliferation. ...
... Studies using animal tissues ex vivo have supported this hypothesis (Lai and Chow, 2010;Kuo et al., 2014). For example, Kuo et al. (2014) recently reported that a 30-minute treatment of traction applied to degraded porcine IVDs was effective in enhancing their nutritional supply and promoting cell proliferation. Determining the degree by which lumbar traction influences fluid movement in vivo in humans will assist in understanding the potential clinical role of this intervention as a treatment for disc disease (Beattie, 2011;Baur et al., 2002). ...
Article
Background: Lumbar traction is a common treatment for low back pain; however its mechanisms of action are poorly understood. It has been hypothesized that a key effect of lumbar traction is its capacity to influence fluid movement within the intervertebral disc (IVD). Objectives: To determine differences in the apparent diffusion coefficient (ADC) obtained with lumbar diffusion-weighted imaging (DWI) of the L5-S1 IVD before, and during, the application of lumbar traction. Design: Case series, repeated measures. Methods: A static traction load of ∼50% of body-weight was applied to the low back using a novel "MRI-safe" apparatus. DWI of the lumbar spine was performed prior to, and during the application of the traction load. Results: Participants were currently asymptomatic and included a young adult group (n = 18) and a middle-aged group (n = 15). The young adult group had a non-significant 2.2% increase in ADC (mean change = 0.03 × 10(-3) mm(2)/s, SD = 0.24, 95% CI = -0.09, 0.15). The ADC for the middle-aged group significantly increased by 20% (mean change of 0.18 × 10(-3) mm(2)/s, SD = 0.19; 95% CI = 0.07, 0.28; p = 0.003; effect size = 0.95). There was an inverse relationship between the ADC obtained before traction and the percent increase in ADC that was measured during traction. Conclusion: Static traction was associated with an increase in diffusion of water within the L5-S1 IVDs of middle-age individuals, but not in young adults, suggesting age-related differences in the diffusion response. Further study is needed to assess the relationship between these findings and the symptoms of back pain. Level of evidence: 4.
... However, noticeable decreases in the lordotic angle of the cervical spine and adverse mechanical tension have been identified through biomechanical studies (Harrison et al., 2002). Also, analysis of the micro-structure of the annulus fibrosus following such traction treatment has found straightened fibers (Kuo et al., 2014), indicating the tensile loading on the soft tissues. ...
... Decreasing the intradiscal pressure is thought to be helpful for retracting prolapsed discs (Cox, 2012), improving nutrient transport and altering the chemical environment of nociceptors in the outer layers of annulus fibrosus (Kuo et al., 2014). The mean IDP decreases were 0.125 MPa and 0.0925 MPa at C4-T1 levels with NS and non-NS traction under 100-N traction force, respectively. ...
Article
Background: Cervical traction is commonly used for treating neck pain. However, few studies have investigated the biomechanical impact such traction has on soft tissues. Objectives: To analyze the biomechanics of cervical traction therapy in a supine position with and without neck support (NS and non-NS). Methods: A finite element model of the cervical spine was constructed to investigate the mechanism behind cervical traction therapy. An axial traction force of 100-N was loaded on the upper surface of C0 to simulate traction weight. Neck support traction was simulated by additionally constraining anterior-posterior motion of the surface of the C4 vertebral lamina. The average von Mises stress, tensile force and motions of related tissues were calculated and compared between the two conditions. Stress in the posterior annulus fibers under flexion was also recorded for comparison. Results: At the C4-C5 and C5-C6 levels, NS traction resulted in less of a decrease in the lordotic angle. At these levels, the highest average stress was distributed in the posterior annulus fibers with non-NS traction and both traction therapies produced greater stress on the posterior annulus fibers than physical flexion. The intradiscal pressure in all intervertebral discs between C4-T1 decreased during both traction therapies. Conclusion: Neck support traction therapy produced less tension on the posterior annulus fibers and ligaments posterior to it at the C4-C5 and C5-C6 levels. In order to minimize the potential harm to soft tissue in clinical practice, it may be beneficial to use a neck support according to the targeted level.
... To overcome the severe ECM digestion and cavities in the NP caused by trypsin in unloaded conditions (Jim et al., 2011), hybrid models that combine a biochemical agent with physiological loading have been adopted (Kuo et al., 2014;Mwale et al., 2008;Périé et al., 2006). Unloaded-trypsin samples showed lower levels of GAGs when compared with loaded-trypsin samples after 7 days of testing in a whole organ IVD culture model (Gawri et al., 2014). ...
Article
The intervertebral disc (IVD) provides flexibility, acts as a shock absorber, and transmits load. Degeneration of the IVD includes alterations in the biomechanics, extracellular matrix (ECM), and cellular activity. These changes are not always perceived, however, IVD degeneration can lead to severe health problems including long-term disability. To understand the pathogenesis of IVD degeneration and suitable testing methods for emerging treatments and therapies, this review documents in-vitro models of IVD degeneration including physical disruption, hyperphysiological loading, ECM degradation by enzyme digestion, or a combination of these methods. This paper reviews and critically analyses the models of degeneration published since the year 2000 in either in human or animal specimens. The results are categorised in terms of the IVD biomechanics, physical attributes, ECM composition, tissue damage and cellularity to evaluate the models with respect to natural human degeneration, and to provide recommendations for clinically relevant models for the various stages of degeneration. There is no one model that replicates the wide range of degenerative changes that occur as part of normal degeneration. However, cyclic overloading replicates many aspects of degeneration, with the advantage of a dose-response allowing the tuning of damage initiated. Models of severe degeneration are currently lacking, but there is potential that combining cyclic overloading and enzymatic digestion will provide model that closely resembles human IVD degeneration. This will provide an effective way to investigate the effects of severe degeneration, and the evaluation of treatments for the IVD, which would generally be indicated at this advanced stage of degeneration.
... It also improves the nutrition of the disc and regulates the chemical environment of pain receptors in the annulus. [21,22] Park et al. [5] performed assisted and unassisted axial traction analyses in their biomechanical study. In the aforementioned study, IDP values decreased in all segments as a result of unassisted traction. ...
Article
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Objectives: This study aims to evaluate the results of lumbar traction treatment at different traction angles and different traction forces using the finite element analysis (FEA). Materials and methods: Computed tomography (CT) images of a healthy 35-year-old male patient who had no history of trauma or fracture were modeled in three-dimensional (3D) with Mimics® software for the lumbosacral spine model. Ligaments and discs were created on the 3D spine model in the SolidWorks® program. The obtained model was sent to the ANSYS version 18 software, and analyses were done non-linearly. All analyses were performed at different angles and forces from the center of the sacral surface to simulate traction therapy. Results: Traction forces applied in the 0° axial direction decreased the intradiscal pressures by creating a similar tensile stress in the annulus fibrosus regions (anterior, posterior, and lateral) without any significant change in lordotic angle. Conclusion: The method used in this study is promising to investigate the benefits of traction therapy. Moreover, individual traction force and direction can be determined to increase the effectiveness of the treatment by using magnetic resonance imaging or CT images in traction therapy.
... Among the existing solutions, traction is very popular but no study has been able to demonstrate its clinical effectiveness in the medium or long term 16 . However, experimental studies have shown that traction tables are likely to increase the height of the intervertebral disc and even reduce the conflicts between the disc and the nerve roots in case of associated sciatica [24][25][26][27] . To date, the lack of evidence of effectiveness is likely to be related to a lack of technical solution, rather than a lack of concept. ...
Article
Low back pain is a common, expensive, and disabling condition in industrialized countries. There is still no consensus for its ideal management. Believing in the beneficial effect of traction, we developed a novel external dynamic distraction device. The purpose of this work was to demonstrate that external distraction allows limiting the pressure exerted in standing-up position on the lower intervertebral discs. Numerical and cadaveric studies were used as complementary approaches. Firstly, we implemented the device into a numerical model of a validated musculoskeletal software (Anybody Modeling System) and we calculated the lower disc pressure while traction forces were applied. Secondly, we performed an anatomical study using a non-formalin preserved cadaver placed in a sitting position. A pressure sensor was placed in the lower discs under fluoroscopic control through a Jamshidi needle. The intradiscal pressure was then measured continuously at rest while applying a traction force of 200 N. Both numerical and cadaveric studies demonstrated a decrease in intradiscal pressures after applying a traction force with the external device. Using the numerical model, we showed that tensile forces below 500 N in total were sufficient. The application of higher forces seems useless and potentially deleterious. External dynamic distraction device is able to significantly decrease the intradiscal pressure in a sitting or standing position. However, the therapeutic effects need to be proven using clinical studies.
... Therapeutic developments may be amenable to local or regional spinal therapy strategies. Several teams have sought to address this critical nutrient transport deficit through mechanical and biological means such as spinal traction [16][17] and enzymatic permeabilization 18 respectively. ...
Article
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Introduction: Apoptosis is a contributing factor to degenerating intervertebral disc (IVD). Disc regeneration has been attempted by transplanting cells into the disc, with some gains in disc height achieved in animal models. Here, we study whether the apoptotic microenvironment affects the transplanted disc cells. Methods: Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were grown in media then starved for 5 days in vitro by not changing the media. Three aspects of apoptotic cell influence on the transplanted cells were tested in a total of 32 samples: 1) the effect of apoptotic cytokines in the media, 2) reduced glucose in the media, and 3) apoptotic cell bodies in the flask. The Trypan Blue, AlamarBlue®, and 1,9-Dimethyl-Methylene Blue assays for sulfated glycosaminoglycan (sGAG) content were performed (n=4). Results: There were significant decreases in cell viability between the control, 25% conditioned media (CM) and starved control group. There were no significant differences in cell number, metabolic activity or sGAG production in cells grown in different conditioned media compared to cells grown in complete media. The cells of the control decreased in viability and number over the 5 days without feeding, then improved dramatically when feeding was resumed. Flasks that received transplanted cells in addition to renewed feeding did not recover as much as the cells in the re-fed group. Conclusions: Cytokines from starved cells negatively impact on the viability of healthy cells. Starving cells that receive new sources of nutrition have even higher viability than transplanted cells. This indicates that altering and improving the nutrient supply problem in the IVD could be a valuable option. Level of Evidence III; Case control studyg.
... This is also corroborated by our finding that the NP portion of TE-IVDs at 16 weeks did not maintain as much disc height, NP hydration, and proteoglycan content as at 2 or 4 weeks. Further, axial distraction using an external fixator can enhance the regenerative capability of cell injection therapy, based on the hypothesis that individually both a distracted segment and cell injection can stimulate disc repair [54][55][56]. ...
Article
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The most common reason that adults in the United States see their physician is lower back or neck pain secondary to degenerative disc disease. To date, approaches to treat degenerative disc disease are confined to purely mechanical devices designed to either eliminate or enable flexibility of the diseased motion segment. Tissue engineered intervertebral discs (TE-IVDs) have been proposed as an alternative approach and have shown promise in replacing native IVD in the rodent tail spine. Here we demonstrate the efficacy of our TE-IVDs in the canine cervical spine. TE-IVD components were constructed using adult canine annulus fibrosis and nucleus pulposus cells seeded into collagen and alginate hydrogels, respectively. Seeded gels were formed into a single disc unit using molds designed from the geometry of the canine spine. Skeletally mature beagles underwent discectomy with whole IVD resection at levels between C3/4 and C6/7, and were then divided into two groups that received only discectomy or discectomy followed by implantation of TE-IVD. Stably implanted TE-IVDs demonstrated significant retention of disc height and physiological hydration compared to discectomy control. Both 4-week and 16-week histological assessments demonstrated chondrocytic cells surrounded by proteoglycan-rich matrices in the NP and by fibrocartilaginous matrices in the AF portions of implanted TE-IVDs. Integration into host tissue was confirmed over 16 weeks without any signs of immune reaction. Despite the significant biomechanical demands of the beagle cervical spine, our stably implanted TE-IVDs maintained their position, structure and hydration as well as disc height over 16 weeks in vivo.
... Traction therapy has been shown to produce some mild benefits to degenerated IVDs as reported in both basic science and clinical literature. For instance, Kuo et al. 22 showed increased porosity and cell viability in discs that received traction treatment in a bioreactor for 3 days. Furthermore, Choi et al. 23 showed improvement with decompression therapy and traction therapy in the preoperative to postoperative treatment course of patients, as measured by decreases in visual analog scale and Oswestry Disability Index scores, whereas their straight leg raise scores increased; however, level 1 evidence for traction therapy is difficult to obtain in the clinic where blinding is impractical. ...
Article
Background: Physical data are lacking on nutrient transport in human intervertebral discs (IVDs), which supports regeneration. Our objective was to study nutrient transport in porcine IVDs to determine the effects of biomechanical and physiological factors. Methods: In vitro testing of whole porcine IVDs was performed under different loading conditions. Fifty cervical, thoracic, and lumbar discs with attached end plates were removed from 4 Yorkshire pigs (90-150 pounds). Discs were placed in Safranin O or Fast Green FCF histological stains in diffusion or diurnal compression-tested groups. The end plate was studied by using polyurethane to block it. Traction was studied with a mechanical testing frame. Discs were cut transversely and photographed. Images were analyzed for depth of annulus fibrosus (AF) stained. The nucleus pulposus (NP) was assigned a staining score. Results: Results showed no difference in AF staining between the two stains (P=0.60). The depth of AF staining did not increase (P=0.60) due to convection or disc height change via diurnal loading. The NP in all open end plate samples was completely stained by day 3. NP staining was decreased in blocked end plate samples (P=0.07) and AF staining was significantly less in traction samples than in diffusion-only samples (P=0.04). Conclusions: This method showed that most small molecule nutrient transport occurs via the end plate. Compressive load was a negligible benefit or hindrance to transport. Traction hindered transport in the short term. This method can be used to study strategies for increasing nutrient transport in IVDs.
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Abstract Introduction In this study, magnetic resonance imaging data was used to (1) model IVD-specific gradients of glucose, oxygen, lactate, and pH; and (2) investigate possible effects of covariate factors (i.e., disc geometry, and mean apparent diffusion coefficient values) on the IVD’s microenvironment. Mathematical modeling of the patient’s specific IVD microenvironment could be important when selecting patients for stem cell therapy due to the increased nutrient demand created by that treatment. Materials and Methods Disc geometry and water diffusion coefficients were extracted from MRIs of 37 patients using sagittal T1-weighted images, T2-weighted images, and ADC Maps. A 2-D steady state finite element mathematical model was developed in COMSOL Multiphysics® 5.4 to compute concentration maps of glucose, oxygen, lactate and pH. Results Concentration of nutrients (i.e., glucose, and oxygen) dropped with increasing distance from the cartilaginous endplates (CEP), whereas acidity levels increased. Most discs experienced poor nutrient levels along with high acidity values in the inner annulus fibrosus (AF). The disc’s physiological microenvironment became more deficient as degeneration progressed. For example, minimum glucose concentration in grade 4 dropped by 31.1% compared to grade 3 (p < 0.0001). The model further suggested a strong effect of the following parameters: disc size, AF and CEP diffusivities, metabolic reactions, and cell density on solute concentrations in the disc (p < 0.05). Conclusion The significance of this work implies that the individual morphology and physiological conditions of each disc, even among discs of the same Pfirrmann grade, should be evaluated when modeling IVD solute concentrations.
Article
Objective The effect of lumbar traction on low back pain (LBP) patients is controversial. Our study aims to assess changes in the intervertebral disc water content after lumbar traction using T2 mapping and explore the correlation between changes in the T2 value and Oswestry Disability Index (ODI)/visual analogue scale (VAS) score. Design Lumbar spine magnetic resonance imaging was performed, and the ODI/VAS scores were recorded in all 48 patients. Midsagittal T2-weighted imaging and T2 mapping were performed to determine the Pfirrmann grade and T2 value. Then, the T2 values were compared between pre- and posttraction, and the correlation between changes in the T2 value and ODI/VAS scores were examined. Results In the traction group, the changes in the nucleus pulposus (NP) T2 values for Pfirrmann grades II-IV and the annulus fibrosus (AF) T2 values for Pfirrmann grade II were statistically significant after traction ( P < 0.05). Changes in the mean NP T2 value of 5 discs in each patient and in the ODI/VAS score showed a strong correlation ( r = 0.822, r = 0.793). Conclusion T2 mapping can be used to evaluate changes in the intervertebral disc water content. Ten sessions of traction resulted in a significant increase in quantitative T2 measurements of the NP in discs for Pfirrmann grade II-IV degeneration and remission of the patients’ clinical symptoms in the following 6 months. Changes in the mean NP T2 value of 5 discs in each patient were strongly correlated with changes in the ODI/VAS score.
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Cervical traction is a therapeutic method used for treating neck pain. As of July 2016 according to the Institute for Health Metrics and Evaluation the healthy life lost per 100000 people from neck pain in India has increased by 18.7% since 1990 as a result of individuals devoting about 10 to 15 hours a day in an undesirable position. This project is an approach using a finite element method for a 30 year old male to investigate the response of soft tissue related to cervical traction therapy affecting the lordosis angle of the cervical spine. Research work is done concerning the material properties of the soft tissues to be incorporated in the model for validation. Once validated the lordosis angle of the cervical region was measured and compared against the lordosis angle of the model when exposed to traction forces. Results of the study gave evidence on the reduction of the lordosis angle and extend at which the lordosis angle is reduced. These results of the study when considered minimize the potential harm to soft tissues during cervical traction therapy and help in allocating the appropriate force on the appropriate position during cervical traction therapy and cervical traction therapy equipment design.
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The intervertebral disc (IVD) is one of the parts of the body most commonly affected by disease, and it is only recently that we have come closer to understanding the reasons for its degeneration, in which nutrient supply plays a crucial role. In this literature review, we discuss the basic principles and characteristics of energy supply and demand to the IVD. Specifically, we review how different metabolites influence IVD cell activity, the effects of mechanical loading on IVD cell metabolism, and differences in energy metabolism of the annulus fibrous and nucleus pulposus cell phenotypes. Determining the factors that influence nutrient supply and demand in the IVD will enhance our understanding of the IVD pathology, and help to elucidate new therapeutic targets for IVD degeneration treatment.
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According to recent data more than 80% of people suffer from back pain, due to an aging and a poor posture, at least once in their life time, and 7~10% of them have chronic spine illness. Researchers over the years have studied on various spinal traction devices that utilize the force of traction, and have also reported clinical test results. However, most existing devices are too complicated and too expensive. In order to solve these problems, we have developed a new device in which the frame moves up and down and at the same time tilting angle of the frame is adjusted. We have analyzed the forces applied on the body as a function of tilting angle. And the result shows that the new device has achieved the force of traction, which is known to be effective for spinal rehabilitation.
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There is growing interest in the role of abnormal asymmetrical posture, which is considered one of the most important etiological factors reported to be associated with mechanical low back pain. This study was conducted to investigate the effect of lumbar extension traction on the pain, function and whole spine sagittal balance as represented in lumbar curvature, thoracic curvature, C7 plumb line, and sacral slope. Eighty patients with chronic mechanical low back pain (CMLBP) and definite hypolordosis were randomly assigned to traction or a control group. The control group (n=40) received stretching exercises and infrared radiation, whereas the traction group (n=40) received lumbar extension traction in addition to stretching exercises and infrared radiation three times a week for 10 weeks. Back pain rating scale, Oswestry Disability Index, and radiological spine sagittal balance parameters in terms of lumbar lordosis, thoracic kyphosis, sacral slope, and positioning of C7 plumb line were measured for all patients at three intervals (before treatment, after 10 weeks of treatment, and at six months follow-up). There was a significant difference between the traction and control groups adjusted to baseline value of outcome at 10 weeks post treatment with respect to lumbar lordotic curve (P=0.000), thoracic kyphosis (P=0.013), sacral slope (P=0.001), C7 plump line distance (p=0.001), while there was no significant difference with respect to pain (p=0.29) and Oswestry Disability Index (ODI) (p=0.1). At 6-months follow-up, there were significant differences between both groups for all the previous variables (p< 0.05). Lumbar extension traction in addition to stretching exercises and infrared radiation improved the spine sagittal balance parameters and decreased the pain and disability in CMLBP.
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Objective: To investigate the effects of lumbar extension traction in patients with unilateral lumbosacral radiculopathy due to L5-S1 disc herniation. Design: A randomized controlled study with six-month follow-up. Setting: University research laboratory. Subjects: Sixty-four patients with confirmed unilateral lumbosacral radiculopathy due to L5-S1 disc herniation and a lumbar lordotic angle less than 39°, randomly assigned to traction or control group. Interventions: The control group (n = 32) received hot packs and interferential therapy, whereas the traction group (n = 32) received lumbar extension traction in addition to hot packs and interferential therapy. Main outcome measures: Absolute rotatory angle, back and leg pain rating scale, Oswestry Disability Index, Modified Schober test, H-reflex (latency and amplitude) and intervertebral movements were measured for all patients three times (before treatment, after 10 weeks of treatment and at six-month follow-up). Results: There was a significant difference between the traction group and the control group adjusted to baseline values at 10 weeks post treatment with respect to: absolute rotatory angle (P < 0.001), Oswestry Disability Index (P = 0.002), back and leg pain (P = 0.009, P = 0.005), Modified Schober test (P = 0.002), latency and amplitude of H-reflex (P = 0.01, P < 0.001), intervertebral movements (P < 0.05). At six-month follow-up there were statistically significant differences between the study and control groups for all the previous variables (P < 0.05). Conclusion: The traction group receiving lumbar extension traction in addition to hot packs and interferential therapy had better effects than the control group with regard to pain, disability, H-reflex parameters and segmental intervertebral movements.
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It is still relatively unclear how intervertebral disc (IVD) cells sense a mechanical stimulus and convert this signal into a biochemical response. Previous studies demonstrated that the cytoskeletal elements are mechano-responsive in many cell types and may contribute to mechano-signalling pathways. The objective of this study was to determine the response of cells from the outer annulus fibrosus (OAF) to physiological levels of cyclic tensile strain; further, cells from the nucleus pulposus (NP) were also subjected to an identical loading regime to compare biological responses across the IVD populations. We determined whether the organisation and expression of the major cytoskeletal elements and their associated accessory proteins are responsive to mechanical stimulation in these cells, and whether these changes correlated with either a catabolic or anabolic phenotype. OAF and NP cells from immature bovine IVD were seeded onto Flexcell® type I collagen coated plates. Cells were subjected to cyclic tensile strain (10 %, 1 Hz) for 60 minutes. Post-loading, cells were processed for immunofluorescence microscopy, RNA extracted for quantitative PCR and protein extracted for Western blotting analysis. F-actin reorganisation was evident in OAF and NP cells subjected to tensile strain; strain induced β-actin at the transcriptional and translational level in OAF cells. β-tubulin mRNA and protein synthesis increased in strained OAF cells, but vimentin expression was significantly inhibited. Cytoskeletal element organisation and expression were less responsive to strain in NP cells. Tensile strain increased type I collagen and differentially regulated extracellular matrix (ECM)-degrading enzymes' mRNA levels in OAF cells. Strain induced type II collagen transcription in NP cells, but had no effect on the transcription of any other genes analysed. Tensile strain induces different mechano-responses in the organisation and/or expression of cytoskeletal elements and on markers of IVD metabolism. Differential mechano-regulation of anabolic and catabolic ECM components in the OAF and NP populations reflects their respective mechanical environments in situ.
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Larger animal models, such as porcine, have been validated as appropriate models of the human disc with respect to biomechanics and biochemistry. They are advantageous for research as the models are relatively straightforward to prepare and easily obtainable for research to perform surgical techniques. The intention of this study was to quantitatively analyze gene expression for collagen and proteoglycan components of the extracellular matrix and for collagenase (MMP-1) in porcine discs of varying ages (Newborn; 2-3weeks, Mature; 6-9 month, Older; 2-3 years). In this study, we observed that the cell number and GAG (glycosaminoglycan) formation dramatically decreased with aging. Also, gene expression in the annulus fibrosus (AF) and nucleus pulposus (NP) cells changed with aging. The level of MMP-1 mRNA increased with age and both type I, II collagens decreased with age. The level of aggrecan mRNA was highest in the mature group and decreased significantly with aging. In the mature group, MMP-1 expression was minimal compared to the newborn group. In AF cells, type II collagen was expressed at a high level in the mature group with a higher level of aggrecan, when aged NP showed a decrease in type II collagen. The model of IVD degeneration in the porcine disc shows many changes in gene expression with age that have been previously documented for human and may serve as a model for studying changes in IVD metabolism with age. We concluded that the porcine model is excellent to test hypotheses related to disc degeneration while permitting time-course study in biologically active systems.
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The present work describes a novel bovine disc organ culture system with long-term maintenance of cell viability, in which degenerative changes can be induced as a prelude to studying repair. Discs were isolated with three different techniques: without endplates (NEP), with bony endplates (BEP) and with intact cartilage endplates (CEP). Swelling, deformation, and cell viability were evaluated in unloaded cultures. Degeneration was induced by a single trypsin injection into the center of the disc and the effect on cell viability and matrix degradation was followed. Trypsin-treated discs were exposed to TGFβ to evaluate the potential to study repair in this system. NEP isolated discs showed >75% maintained cell viability for up to 10 days but were severely deformed, BEP discs on the other hand maintained morphology but failed to retain cell viability having only 27% viable cells after 10 days. In CEP discs, both cell viability and morphology were maintained for at least 4 weeks where >75% of the cells were still viable. To mimic proteoglycan loss during disc degeneration, a single trypsin injection was administered to the center of the disc. This resulted in 60% loss of aggrecan, after 7 days, without affecting cell viability. When TGFβ was injected to validate that the system can be used to study a repair response following injection of a bio-active substance, proteoglycan synthesis nearly doubled compared to baseline synthesis. Trypsin-treated bovine CEP discs therefore provide a model system for studying repair of the degenerate disc, as morphology, cell viability and responsiveness to bio-active substances were maintained.
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The management of spinal tuberculosis, especially in children, is controversial. In children, vertebral destruction is more severe than adults because of the cartilaginous nature of their bone. Modern chemotherapy has significantly decreased mortality in spinal tuberculosis, but morbidity remains high. Without early surgery, patients can develop severe kyphosis leading to respiratory insufficiency, painful costopelvic impingement and paraplegia. Lumbar kyphosis results in early degenerative lumbar canal stenosis and is cosmetically unacceptable. We report a paediatric case of atypical spinal tuberculosis demonstrating the need for early surgical intervention to prevent significant spinal instability and neurologic deficit. A 12-year-old girl presented with increasing ambulatory difficulty and double incontinence 4 months after initiating treatment for pulmonary tuberculosis. There was no history of traumatic injury. Examination revealed severe lower limb neurologic deficit, with hypotonia, areflexia, marked sensory loss, and grade 0/5 power in both lower limbs. Plain radiographs and magnetic resonance imaging (MRI) demonstrated grade IV posterior listhesis of the L2 vertebral body over L3, cauda equina compression and bilateral psoas abscesses. Erosion of both the body and pedicle of L2 was observed. Both serology and pus drained from the psoas abscesses were negative for microorganisms. The patient underwent an L2 vertebrectomy via a left retroperitoneal approach. A titanium cage packed with autologous bone graft was inserted, and the spine was stabilized by fixation with screw and rods. Histopathology confirmed a diagnosis of tuberculosis. Eighteen months following the procedure, the patient has regained some power in her right leg and has completed her course of anti-tuberculous chemotherapy, but remains wheelchair-bound. To our knowledge, this is the first reported case of posterior listhesis secondary to spinal tuberculosis. Here, we discuss the possible management options in such a case, and the indications for surgery. As the global HIV/AIDS epidemic causes a resurgence in tuberculosis, increased awareness among the medical community regarding the atypical presentations of spinal tuberculosis is necessitated; both in the developing world where advanced clinical presentations are common, and in the developed world where spinal tuberculosis is an often-neglected diagnosis.
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Because previous studies have suggested that motorized non-surgical spinal decompression can reduce chronic low back pain (LBP) due to disc degeneration (discogenic low back pain) and disc herniation, it has accordingly been hypothesized that the reduction of pressure on affected discs will facilitate their regeneration. The goal of this study was to determine if changes in LBP, as measured on a verbal rating scale, before and after a 6-week treatment period with non-surgical spinal decompression, correlate with changes in lumbar disc height, as measured on computed tomography (CT) scans. A retrospective cohort study of adults with chronic LBP attributed to disc herniation and/or discogenic LBP who underwent a 6-week treatment protocol of motorized non-surgical spinal decompression via the DRX9000 with CT scans before and after treatment. The main outcomes were changes in pain as measured on a verbal rating scale from 0 to 10 during a flexion-extension range of motion evaluation and changes in disc height as measured on CT scans. Paired t-test or linear regression was used as appropriate with p < 0.05 considered to be statistically significant. We identified 30 patients with lumbar disc herniation with an average age of 65 years, body mass index of 29 kg/m2, 21 females and 9 males, and an average duration of LBP of 12.5 weeks. During treatment, low back pain decreased from 6.2 (SD 2.2) to 1.6 (2.3, p < 0.001) and disc height increased from 7.5 (1.7) mm to 8.8 (1.7) mm (p < 0.001). Increase in disc height and reduction in pain were significantly correlated (r = 0.36, p = 0.044). Non-surgical spinal decompression was associated with a reduction in pain and an increase in disc height. The correlation of these variables suggests that pain reduction may be mediated, at least in part, through a restoration of disc height. A randomized controlled trial is needed to confirm these promising results. NCT00828880.
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The insufficient investigations on the changes of spinal structures during traction prevent further exploring the possible therapeutic mechanism of cervical traction. A blind randomized crossover-design study was conducted to quantitatively compare the intervertebral disc spaces between axial and anterior lean cervical traction in sitting position. A total of 96 radiographic images from the baseline measurements, axial and anterior lean tractions in 32 asymptomatic subjects were digitized for further analysis. The intra- and inter-examiner reliabilities for measuring the intervertebral disc spaces were in good ranges (ICCs = 0.928-0.942). With the application of anterior lean traction, the statistical increases were detected both in anterior and in posterior disc spaces compared to the baseline (0.29 mm and 0.24 mm; both P < 0.01) and axial traction (0.16 mm and 0.35 mm; both P < 0.01). The greater intervertebral disc spaces obtained during anterior lean traction might be associated with the more even distribution of traction forces over the anterior and posterior neck structures. The neck extension moment through mandible that generally occurred in the axial traction could be counteracted by the downward force of head weight during anterior lean traction. This study quantitatively demonstrated that anterior lean traction in sitting position provided more intervertebral disc space enlargements in both anterior and posterior aspects than axial traction did. These findings may serve as a therapeutic reference when cervical traction is suggested.
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Nuclei pulposi were dissected from lumbar discs of radiologically normal human spines of cadavers aged 17, 20 and 21 years. Proteoglycans were extracted with 4 M guanidine hydrochloride (dissociative conditions) with proteinase inhibitors and isolated as A1 fractions by associative density-gradient centrifugation. Aggregating and non-aggregating proteoglycans were separated by Sepharose 2B chromatography. Both aggregating and non-aggregating proteoglycans contained a keratan sulphate-rich region as isolated by chondroitinase/trypsin/chymotrypsin digestion and Sepharose CL-6B chromatography. Agarose/acrylamide-gel electrophoresis of individual fractions of a Bio-Gel A-50m dissociative-column separation of the aggregating proteoglycans revealed two, well-separated bands: S and F, the slower and faster migrating bands respectively. The non-aggregating proteoglycan fractions were eluted under associative conditions (0.5 M-sodium acetate, pH 6.8) and migrated as a single band in the electrophoretic system. The gel-electrophoretic heterogeneity of the aggregating proteoglycans was still evident after hydroxylamine fragmentation and removal of the hyaluronate-binding portion of the molecule. Dissociative density-gradient centrifugation of the aggregating proteoglycans partially separated the Band-S proteoglycans from the Band-F population. Subsequent dissociative chromatography of the high-buoyant-density Band F proteoglycans permitted discrimination of this band into two gel-electrophoresis-distinguishable populations (Bands F-1 and F-2). Enzyme-linked immunosorbent assays with a monoclonal antibody that recognized keratan sulphate demonstrated that the D1 fraction containing the Band F-1 proteoglycans was enriched in keratan sulphate compared with the total aggregating or non-aggregating pool of proteoglycans. The proteoglycans of young adult nucleus pulposus could then be ascribed to one of four structurally and/or electrophoretically distinct populations: (1) the non-aggregating population, which comprised about 70% of the total extractable proteoglycans; (2) the aggregating pool, comprising: (a) Band F-1 proteoglycans, which had a relatively large hydrodynamic size, uronate/protein weight ratio, were enriched in keratan sulphate and had a high buoyant density; (b) Band S proteoglycans, which migrated slower in agarose/acrylamide gels, had a smaller hydrodynamic size, lower buoyant density and a lower uronate/protein ratio than the Band F-1 population; (c) Band F-2 proteoglycans, which were lower in buoyant density, smaller in hydrodynamic size and slightly faster in electrophoretic mobility than the Band F-1 proteoglycans.
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Non-aggregating proteoglycans of differing average hydrodynamic volumes were prepared from nuclei pulposi and anuli fibrosi of three human lumbar spines and characterized by biochemical and immunochemical analyses. The hexose-to-hexuronate and protein-to-hexuronate ratios increased with decreasing hydrodynamic volume. Analysis by composite agarose/polyacrylamide-gel electrophoresis has demonstrated two aggregating subpopulations [McDevitt, Jahnke & Green (1982) Trans. Annu. Meet. Orthop. Res. Soc. 7, 50]. In the present study, electrophoresis of the non-aggregating pools has shown three additional subpopulations, here named bands III, IV and V. The two smallest proteoglycan pools from each tissue contained two and three components respectively. These components were isolated by preparative electrophoresis and analysed. Band III was a proteoglycan richer in keratan sulphate than in chondroitin sulphate; band IV was a proteoglycan richer in chondroitin sulphate than in keratan sulphate; band V contained only chondroitin sulphate. Unsaturated disaccharides prepared from the chondroitin sulphate of all bands were predominantly 6-sulphated, with only 5-15% 4-sulphated. The molecular masses of the chondroitin sulphate and keratan sulphate did not differ between the bands. The amino acid composition of band III differed from that of band IV. Thus three distinct subpopulations of non-aggregating proteoglycan were demonstrated in the human intervertebral disc.
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Previous trials to assess the efficacy of lumbar traction for back pain have been methodologically flawed. To avoid these shortcomings, we conducted a randomised controlled trial in which high-dose traction was compared with sham traction. The sham traction was given with a specially developed brace that tightens in the back during traction. To the patient, the experience is that of traction. The patients and outcome assessor were blinded for the assigned treatment. 151 patients with at least six weeks of non-specific low back pain were randomised. Intention to treat analysis showed no differences between the groups on all outcome measures (patients' global perceived effect, severity of main complaints, functional status and pain); all 95% confidence intervals included the value zero. The number of withdrawals from treatment, loss to follow-up, and protocol deviations was low. Consequently, the per-protocol analysis showed results similar to the intention to treat analysis. Subgroup analyses did not show any group for which traction might seem promising. Our data do not support the claim that traction is effective for patients with low back pain.
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To determine if vertebral bone densities or vertebral body sizes contribute to gender differences in vertebral bone mass in adults. Cancellous and cortical bone densities and dimensions of three lumbar vertebrae in 25 women and 18 men were measured with quantitative computed tomography (CT) and statistically analyzed. Neither cancellous nor cortical vertebral bone densities differed in healthy adults. Vertebral bodies in women had lower cross-sectional areas (8.22 cm2 +/- 1.09 [standard deviation] versus 10.98 cm2 +/- 1.25, P < .001) and volumes (22.42 cm3 +/- 2.40 versus 30.86 cm3 +/- 2.6, P < .001). These differences also were evident in men and women matched for age, weight, vertebral bone density, and vertebral body height. Overall cross-sectional areas of vertebral bodies are 25% smaller in women than men. Vertebral bone densities do not differ between sexes. Estimates of mechanical stress within vertebral bodies are 30%-40% higher in women than men for equivalent applied loads. Smaller vertebral bodies in women confer biomechanical disadvantages that may contribute to more vertebral fractures in elderly women.
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Recent studies of the spine in adolescents who have sustained trauma have shown injuries to the growth zone, whereas injuries to the vertebral body have been described in other studies of only adults. There are also reports on different clinical signs and radiological findings in adolescents with lumbar disc herniation when compared to adults. In order to find an explanation for these differences between adolescents and adults, this experimental study was performed. Six cadaveric lumbar motion segments (vertebral body-disc-vertebral body) obtained from three young male pigs and six lumbar motion segments obtained from three mature male pigs were tested in axial compression to failure. All units were examined with plain radiography and magnetic resonance imaging before and after compression. After the compression, histological samples were taken from the injury site. In the adolescents, a fracture was consistently found in the endplate through the posterior part of the growth zone, displacing the anulus fibrosus with a bony fragment at the point of insertion to the vertebra. This type of injury could not be detected in any of the adults; instead, there was a fracture of the vertebra in four cases, and in two cases, a rupture of the anulus fibrosus without a bony fragment was seen. This study showed that, when compressed to failure, the weakest part of the lumbar spine of the adolescent pig differs from that of the mature pig in the same way that studies on human spinal units have shown.
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The literature on the efficacy of traction in the treatment of low back pain (LBP) is conflicting. The aim of this study was to examine its efficacy in this disorder. Forty-two patients with at least 6 weeks of nonspecific LBP were selected. Demographic data were obtained. All patients completed the Oswestry disability index (ODI) to assess disability and the 10-cm visual analog scale (VAS) for evaluation of pain. Subjects were randomly assigned into group 1, receiving only standard physical therapy, or group 2, receiving standard physical therapy with conventional lumbar traction. Standard physical therapy consisted of local heat, ultrasound for the lumbar region, and an active exercise program, given for ten sessions in all. The subjects received instruction on correct posture and recommended therapeutic exercises. They were reevaluated at the end of treatment and at 3-month follow-up. The mean outcome measures were global improvement and satisfaction with the therapy, as well as disability by ODI and pain by VAS. There were no group differences in terms of demographic and baseline clinical characteristics. There was a significant reduction in pain intensity and disability at the end of treatment in both groups. There was complete or mild improvement in 47.6% of group 1 and 40% of group 2. The satisfaction rate with both treatments was more than 70% immediately after the therapies. During the 3-month period, the outcome measures except disability remained statistically stable, with no difference amongst groups. Disability was significantly reduced at follow-up in both groups. Of the patients, 51% continued with the recommended exercises and had significantly lower disability scores than those who did not continue with the exercises. Pain and global improvement were also better in this group, but the difference was not statistically significant. In conclusion, no specific effect of traction on standard physical therapy was observed in our study group. We suggest focusing on back education and exercise therapy in the management of patients suffering from this chronic condition.
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Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo models have often been used for this purpose. However, there are many differences in cell population, tissue composition, disc and spine anatomy, development, physiology and mechanical properties, between animal species and human. Both naturally occurring and induced degenerative changes may differ significantly from those seen in humans. This paper reviews the many animal models developed for the study of IVD degeneration aetiopathogenesis and treatments thereof. In particular, the limitations and relevance of these models to the human condition are examined, and some general consensus guidelines are presented. Although animal models are invaluable to increase our understanding of disc biology, because of the differences between species, care must be taken when used to study human disc degeneration and much more effort is needed to facilitate research on human disc material.
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To investigate the influence of targeted trypsin digestion and 16 hours compression loading on MR parameters and the mechanical and biochemical properties of bovine disc segments. Twenty-two 3-disc bovine coccygeal segments underwent compression loading for 16 hours after the nucleus pulposus (NP) of each disc was injected with a solution of trypsin or buffer. The properties of the NP and annulus fibrosus (AF) tissues of each disc were analyzed by quantitative MRI, biochemical tests, and confined compression tests. Loading had a significant effect on the MR properties (T(1), T(2), T(1rho), MTR, ADC) of both the NP and AF tissues. Loading had a greater effect on the MR parameters and biochemical composition of the NP than trypsin. In contrast, trypsin had a larger effect on the mechanical properties. Our data also indicated that localized trypsin injection predominantly affected the NP. T(1rho) was sensitive to loading and correlated with the water content of the NP and AF but not with their proteoglycan content. Our studies indicate that physiological loading is an important parameter to consider and that T(1rho) contributes new information in efforts to develop quantitative MRI as a noninvasive diagnostic tool to detect changes in early disc degeneration.
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Many new treatments for degeneration of the intervertebral disc are being developed which can be delivered through a needle. These require testing in model systems before being used in human patients. Unfortunately, because of differences in anatomy, there are no ideal animal models of disc degeneration. Bovine explant model systems have many advantages but it is not possible to inject any significant volume into an intact disc. Therefore we have attempted to mimic disc degeneration in an explant bovine model via enzymatic digestion. Bovine coccygeal discs were incubated with different concentrations of the proteolytic enzymes, trypsin and papain, and maintained in culture for up to 3 weeks. A radio-opaque solution was injected to visualise cavities generated. Degenerative features were monitored histologically and biochemically (water and glycosaminoglycan content, via dimethylmethylene blue). The central region of both papain and trypsin treated discs was macro- and microscopically fragmented, with severe loss of metachromasia. The integrity of the surrounding tissue was mostly in tact with cells in the outer annulus appearing viable. Biochemical analysis demonstrated greatly reduced glycosaminoglycan content in these compared to untreated discs. We have shown that bovine coccygeal discs, treated with proteolytic enzymes can provide a useful in vitro model system for developing and testing potential new treatments of disc degeneration, such as injectable implants or biological therapies.
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Study design: An in situ study using whole-organ culture system. Objective: To study the effect of disc degeneration at different stages on its rheological and dynamic properties and to investigate the efficacy of exogenous cross-linking therapy. Summary of background data: Disc degeneration can involve protein denaturation or microdefects to the disc's collagen fiber network. A disc degeneration model using whole-organ culture technique can be effectively used for the screening of treatments of degenerated discs. Exogenous cross-linking therapy has been shown to enhance the mechanical properties of the disc by cross-linking collagen. However, the efficacy of this therapy on the degenerated disc is unclear. Methods: A total of 40 porcine thoracic discs were assigned to 5 groups: intact discs, moderately degenerated discs, moderately degenerated discs with cross-linker augmentation, severely degenerated discs, and severely degenerated discs with cross-linker augmentation. The disc degeneration was simulated by trypsin digestion and mechanical fatigue loading. Rheological properties, dynamic properties, water content, and histological analysis were conducted after a 7-day incubation. Results: The mechanical properties of moderate degenerated discs significantly decrease both in rheological and dynamic properties, and laminate structure disorganization was observed. Mechanical defects of severely degenerated discs resulted in disc height loss, an increase in the aggregate modulus and stiffness modulus, and a decrease in the damping coefficient, hydraulic permeability, and water content. Cross-linker augmentation significantly recovered mechanical properties of moderately degenerated discs and restored the water content compared with the intact disc. However, the augmentation did not fully repair the severely degenerated discs. Conclusion: Trypsin-induced extracellular matrix damage resulted in a change of the disc's biomechanics. Cross-linker augmentation recovers the rheological and dynamic properties of moderately degenerated discs but not of the severely degenerated discs. The genipin cross-linker may be able to improve the proteoglycan depletion effect in the nucleus pulposus but may not be effective to restore the structural damage in the collagen molecule of the anulus fibrosus.
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Intervertebral disks are biologically regulated by the maintenance of a balance between the anabolic and catabolic activities of disk cells. Therapeutic agents, initially evaluated using in vitro studies on disk cells and explants, have been used as intradiscal injections in preclinical settings to test in vivo efficacy. These include anabolic growth factors, other biostimulatory agents, and antagonistic agents against matrix-degrading enzymes and cytokines. Additional work is needed to identify patient populations, using methods such as MRI, and to better understand the mechanism of healing. Clinical trials are underway for a few of these agents and other promising candidates are on the horizon.
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The main aim of this study was to provide anatomical data on the heights of the human intervertebral discs for all levels of the thoracic spine by direct and radiographic measurements. Additionally, the heights of the neighboring vertebral bodies were measured, and the prediction of the disc heights based only on the size of the vertebral bodies was investigated. The anterior (ADH), middle (MDH) and posterior heights (PDH) of the discs were measured directly and on radiographs of 72 spine segments from 30 donors (age 57.43 ± 11.27 years). The radiographic measurement error and the reliability of the measurements were calculated. Linear and non-linear regression analyses were employed for investigation of statistical correlations between the heights of the thoracic disc and vertebrae. Radiographic measurements displayed lower repeatability and were shorter than the anatomical ones (approximately 9% for ADH and 37% for PDH). The thickness of the discs varied from 4.5 to 7.2 mm, with the MDH approximately 22.7% greater. The disc heights showed good correlations with the vertebral body heights (R(2), 0.659-0.835, P-values < 0.005; anova), allowing the generation of 10 prediction equations. New data on thoracic disc morphometry were provided in this study. The generated set of regression equations could be used to predict thoracic disc heights from radiographic measurement of the vertebral body height posterior. For the creation of parameterized models of the human thoracic discs, the use of the prediction equations could eliminate the need for direct measurement on intervertebral discs. Moreover, the error produced by radiographic measurements could be reduced at least for the PDH.
Article
An ex vivo biomechanical study on the rheological properties of healthy porcine and degenerated human intervertebral disc. To quantify the effect of loading history, loading magnitude, fatigue loading, and degeneration on disc rheology. Disc rheological parameters, i.e., the aggregate modulus (HA) and hydraulic permeability (k) regulate the mechanical and biologic function of disc. The knowledge of effects of loading condition and degeneration on disc rheology can be beneficial for the design of new disc/nucleus implants or therapy. The following 4 phases of experiments were conducted to find the changes of disc rheological properties: (1) Effect of loading history during 1-hour creep (640 N) and relaxation (20% strain) test. (2) Effect of loading magnitude (420 N vs. 640 N) during the creep test. (3) Effect of fatigue loading (420 N, 5 Hz for 0.5, 1, and 2 hours) on the creep loading behavior. (4) Difference of healthy porcine and degenerated human discs during creep loading. The experimental data were fitted with linear biphasic model. The aggregate modulus increased but hydraulic permeability decreased during creep loading. The aggregate modulus decreased but the hydraulic permeability did not change significantly during relaxation loading. The higher creep loading increased the aggregate modulus but decreased the hydraulic permeability. The fatigue loading did not change the aggregate modulus significantly, but decreased hydraulic permeability. Comparing the degenerated human disc to the healthy porcine disc, the aggregate modulus was higher but the hydraulic permeability was lower. The external loading and degeneration induce disc structural changes, e.g., the disc water content and interstitial matrix porosity, hence affect the disc rheological properties. The increase of aggregate modulus may be due to the reduction of disc hydration level, whereas the decrease of hydraulic permeability may be because of the shrinkage of disc matrix pores.
Article
An ex vivo degenerative intervertebral disc (IVD) organ culture system was established for the screening of disc regeneration agents. Its application was demonstrated by a stem cell and growth factor-based therapeutic approach for the amelioration of IVD. An ex vivo culture system using chymopapain to partially digest nucleus proposus tissue was established to mimic human IVD degeneration. This system was then used for the evaluation of different therapeutic regimens including: mesenchymal stem cell derived from eGFP-transgenic porcine (MSC-GFP), platelet-rich plasma (PRP) and MSC-GFP/PRP combined treatment, and confirmed in in vivo animal model. Chondrogenic-specific gene products including Col II and aggrecan were found upregulated and chondrogenic matrix deposition increased, as evident by sustained fluorescent signals over 4 weeks, in the MSC-GFP implanted group. Previously, we demonstrated in vitro stage-specific chondrogenesis of MSC by chondrocytic commitment. These same molecules upregulated for chondrogenesis were also observed in MSC-GFP group. PRP that has been shown to promote nucleus pulposus (NP) regeneration also resulted in significant increased levels of mRNA involved in chondrogenesis and matrices accumulation. The ex vivo IVD regeneration results were repeated and supported by in vivo porcine degenerative system. Moreover, the disc height index (DHI) was significantly increased in both in vivo MSC-GFP and PRP regeneration groups. Unexpectedly, the MSC-GFP/PRP combined therapy demonstrated an inclination towards osteogenesis in ex vivo system. The ex vivo degenerative IVD culture system described in this study could serve as an alternative and more accessible model over large animal model. This system also provides a high-throughput platform for screening therapeutic agents for IVD regeneration.
Article
Poor nutritional supply to the intervertebral disc is believed to be an important factor leading to disc degeneration. However, little is known regarding nutritional transport in human annulus fibrosus (AF) and its relation to tissue morphology. We hypothesized that solute diffusivity in human AF is anisotropic and inhomogeneous, and that transport behaviors are associated with tissue composition and structure. To test these hypotheses, we measured the direction-dependent diffusivity of a fluorescent molecule (fluorescein, 332 Da) in three regions of AF using a fluorescence recovery after photobleaching (FRAP) technique, and associated transport results to the regional variation in water content and collagen architecture in the tissue. Diffusivity in AF was anisotropic, with higher values in the axial direction than in the radial direction for all regions investigated. The values of the diffusion coefficient ranged from 0.38 +/- 0.25 x 10(-6) cm(2)/s (radial diffusivity in outer AF) to 2.68 +/- 0.84 x 10(-6) cm(2)/s (axial diffusivity in inner AF). In both directions, diffusivity decreased moving from inner to outer AF. Tissue structure was investigated using both scanning electron microscopy and environmental scanning electron microscopy. A unique arrangement of microtubes was found in human AF. Furthermore, we also found that the density of these microtubes varied moving from inner to outer AF. A similar trend of regional variation was found for water content, with the highest value also measured in inner AF. Therefore, we concluded that a relationship exists among the anisotropic and inhomogeneous diffusion in human AF and the structure and composition of the tissue.
Article
The goal of this study was to develop a nondestructive radial compression technique and to investigate the viscoelastic behavior of the rat tail disc under repeated radial compression. Rat tail intervertebral disc underwent radial compression relaxation testing and creep testing using a custom-made gravitational creep machine. The axisymmetric viscoelasticity and time-dependent recovery were determined. Different levels of hydration (with or without normal saline spray) were supplied to evaluate the effect of changes in viscoelastic properties. Viscoelasticity was found to be axisymmetric in rat-tail intervertebral discs at four equidistant locations. Complete relaxation recovery was found to take 20 min, whereas creep recovery required 25 min. Hydration was required for obtaining viscoelastic axisymmetry and complete viscoelastic recovery.
Article
Although low back pain can be principally produced or increased during action, it may also be induced or enhanced in the morning after bed rest. During bed rest, tissue edema (increased water content) may occur. In this study, we measured the changes in water content in the intervertebral disc and the paravertebral muscle before and after bed rest using a magnetization transfer magnetic resonance imaging (MT-MRI) technique that permits measuring water content in tissues. A total of 20 student volunteers were enrolled in this study. MT-MRI evaluation was performed before and after bed rest. To measure water content in the intervertebral disc and paravertebral muscle, two MRI sequences were performed using MT pulse-off and MT pulse-on. Based on the two images obtained, the equivalent cross-relaxation rate (ECR) was calculated. The ECR for intervertebral discs was significantly lower after bed rest than before bed rest (P < 0.01). The ECR for paravertebral equivalent cross-relaxation rate muscles was significantly higher after bed rest than before bed rest (P < 0.05). We obtained results indicating that after bed rest the water content in the intervertebral disc and the paravertebral muscle was increased and decreased, respectively.
Article
An in vitro biomechanical study using adolescent porcine discs. To find the effect of fatigue loading and rest on the dynamic properties of healthy intervertebral disc. The fatigue loading is a risk factor for low back pain. The disc dynamic properties describe the shock attenuation capability of disc. Knowledge of effect of fatigue loading and rest on the disc dynamic properties can be beneficial for the study of fatigue loading induced spinal disorder. Specimens were divided into short-term (0.5 hours at 5 Hz, n = 9) and long-term (2 hours at 5 Hz, n = 9) fatigue loading groups. The specimen was applied with fatigue loading, followed by a 12-hours rest, and then applied with the second fatigue loading again. The impulse loading was applied at 0, 10, 20, and 30 minutes during short-term group and at 0, 0.5, 1, and 2 hours during long-term group using a drop-tower apparatus. The stiffness, damping coefficient, and ratio were calculated using impulse loading information. Dynamic properties between first and second fatigue loading were compared. The stiffness increased, but the damping coefficient and ratio decreased with fatigue loadings. A 12-hours rest can fully restore the dynamic properties of fatigue loaded disc to original status. However, the degradation of dynamic properties during the subsequent fatigue loading was faster than the previous fatigue loading if the disc experienced a long-term fatigue loading. A 12-hours rest can largely restore disc dynamic properties during fatigue loading; hence fully recover disc dynamic properties. A long-term fatigue loading squeezes the disc fluid and injures the disc integrity. The 12-hours rest can recover the fluid loss but not the injury of disc. Hence, the disc degradation during the second fatigue loading was faster than the first fatigue loading.
Article
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.
Article
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.
Article
The object of this study was to examine the effect of vertebral axial decompression on pressure in the nucleus pulposus of lumbar discs. Intradiscal pressure measurement was performed by connecting a cannula inserted into the patient's L4-5 disc space to a pressure transducer. The patient was placed in a prone position on a VAX-D therapeutic table and the tensionometer on the table was attached via a pelvic harness. Changes in intradiscal pressure were recorded at resting state and while controlled tension was applied by the equipment to the pelvic harness. Intradiscal pressure demonstrated an inverse relationship to the tension applied. Tension in the upper range was observed to decompress the nucleus pulposus significantly, to below -100 mm Hg.
Article
The outcomes of vertebral axial decompression (VAX-D) therapy for patients with low back pain from various causes are reported. Data was collected from twenty-two medical centers for patients who received VAX-D therapy for low back pain, which was sometimes accompanied by referred leg pain. Only patients who received at least ten sessions and had a diagnosis of herniated disc, degenerative disc, or facet syndrome, which were confirmed by diagnostic imaging, were included in this study; a total of 778 cases. The average time between the initial onset of symptoms and the beginning of this therapy was 40 months, and it was four months or more in 83% of the cases. The data contained the patients' quantitative assessments of their own pain, mobility, and ability to carry out the usual 'activities of daily living'. The treatment was successful in 71% of the 778 cases, when success was defined as a reduction in pain to 0 or 1, on a 0 to 5 scale. Improvements in mobility and activities of daily living correlated strongly with pain reduction. The causes of back pain and their relationship to this therapy are also discussed.
Article
We conducted intradiscal pressure measurements with one volunteer performing various activities normally found in daily life, sports, and spinal therapy. The goal of this study was to measure intradiscal pressure to complement earlier data from Nachemson with dynamic and long-term measurements over a broad range of activities. Loading of the spine still is not well understood. The most important in vivo data are from pioneering intradiscal pressure measurements recorded by Nachemson during the 1960s. Since that time, there have been few data to corroborate or dispute those findings. Under sterile surgical conditions, a pressure transducer with a diameter of 1.5 mm was implanted in the nucleus pulposus of a nondegenerated L4-L5 disc of a male volunteer 45-years-old and weighing 70 kg. Pressure was recorded with a telemetry system during a period of approximately 24 hours for various lying positions; sitting positions in a chair, in an armchair, and on a pezziball (ergonomic sitting ball); during sneezing, laughing, walking, jogging, stair climbing, load lifting during hydration over 7 hours of sleeping, and others. The following values and more were measured: lying prone, 0.1 MPa; lying laterally, 0.12 MPa; relaxed standing, 0.5 MPa; standing flexed forward, 1.1 MPa; sitting unsupported, 0.46 MPa; sitting with maximum flexion, 0.83 MPa; nonchalant sitting, 0.3 MPa; and lifting a 20-kg weight with round flexed back, 2.3 MPa; with flexed knees, 1.7 MPa; and close to the body, 1.1 MPa. During the night, pressure increased from 0.1 to 0.24 MPa. Good correlation was found with Nachemson's data during many exercises, with the exception of the comparison of standing and sitting or of the various lying positions. Notwithstanding the limitations related to the single-subject design of this study, these differences may be explained by the different transducers used. It can be cautiously concluded that the intradiscal pressure during sitting may in fact be less than that in erect standing, that muscle activity increases pressure, that constantly changing position is important to promote flow of fluid (nutrition) to the disc, and that many of the physiotherapy methods studied are valid, but a number of them should be re-evaluated.
Article
Magnetic resonance imaging was used to measure the changes in volume of the lumbar intervertebral disc in vivo during a load cycle. To measure changes in volume of the lumbar intervertebral disc during a load cycle and relate these changes to changes in fluid content. There have been very few experiments conducted to measure the volume and fluid changes in intervertebral discs in vivo. 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. 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. Load-induced changes in disc volume can be detected and measured using magnetic resonance imaging.
Article
OBJECTIVE.: To compile a database of disc height, vertebral height and sagittal plane displacement from lateral radiographic views of the lumbar spine, valid for male and female subjects in the age range 16-57 years. The protocols used to measure these parameters compensate for distortion in central projection, off-centre position, axial rotation and lateral tilt of the spine as well as for variation in radiographic magnification and stature. STUDY DESIGN.: The study comprised designing and testing of measurement protocols, together with subsequent data collection from archive radiographs. BACKGROUND.: Attempts to quantify primary mechanical damage to lumbar vertebrae and discs have been limited due to imprecision when measuring disc height, vertebral height and sagittal plane displacement. Age-related, normative values for these parameters were not previously available. Consequently, important issues like the effectiveness of past and present guidelines for safe manual handling with respect to prevention of overload injuries could not be resolved and judgement on pathological alterations in the morphology of the individual lumbar spine could only be performed in a qualitative, subjective manner. METHODS.: Based on the analysis of vertebral contours in the lateral radiographic image of the lumbar spine, new protocols for measuring disc height, vertebral height and sagittal plane displacement were developed. The measured data are virtually independent of distortion, axial rotation and lateral tilt. Furthermore, description of height and displacement using dimensionless parameters guarantees independence of radiographic magnification and stature. Subjective influence in the measurement procedure was minimized by automatic computation of contour-landmarks and derived parameters. Measurement errors were assessed from sets of radiographs of spine specimens and serial flexion-extension radiographs; interobserver and intraobserver errors were assessed from repeated measurements of lateral views. For compilation of a database, measurements were performed of a set of 892 lateral views of the lumbar spine of male and female subjects between 16 and 57 years of age. Data from pathologically deformed vertebrae or discs, or from motion segments exhibiting spondylolisthesis or retrolisthesis were excluded by normal radiological inspection; data from spines showing normal, age-related degenerative changes were included. RESULTS.: The new protocols allow height and displacement of lumbar vertebrae as well as height of lumbar discs to be measured for all motion segments on a lateral view, rather than just those vertebrae or discs close to the central beam, to facilitate recognition of localized abnormalities. Since the results are independent of exposure geometry, retrospective investigations are feasible. The relative measurement error in vertebral height amounts to 2.2%; for a vertebra of 30 mm height this corresponds to an error of approximately 0.7 mm. The error in sagittal plane displacement amounts to 0.015 (measured in units of mean vertebral depth); for a vertebra of 35 mm depth this corresponds to an error of 0.5 mm. The relative error in disc height amounts to 4.15%; for a disc of 10 mm height this corresponds to an error of approximately 0.5 mm. For both genders, the database contains age-dependent, normative values of disc height, vertebral height and sagittal plane displacement. In addition, the database describes intersegmental shape correlation, i.e. the relation between height of neighbouring discs and between height as well as displacement of neighbouring vertebrae. On average, height of lumbar vertebrae is larger in females than in males; height of lumbar discs is larger in males than in females and shows a minute dependence on age in males; in both genders, sagittal plane displacement increases, but only by a small amount, with age. CONCLUSIONS.: The new measurement protocols for disc height, vertebral height and sagittal plane displacement, together with the database of normative age-related values, permit quantitative assessment of the prevalence of pathological morphological changes in the human lumbar spine. The new method and the database will serve to explore the effect of potentially detrimental influences such as high spinal loading and to provide quantitative documentation of existing injury to vertebrae and discs in individual cases.
Article
Magnetic resonance imaging (MRI) was used to measure the changes in the volume (and fluid content) of the lumbar intervertebral discs (L1-L2, L2-L3, L3-L4, L4-L5) in five normal subjects. For each subject, MRI scans were taken at the end of a normal day and again on the following morning (after a night's bed rest). Ten further scans were taken during an 8-h protocol consisting of alternate periods of walking (40 min) and scanning (10 min). On average, 1) disc volume increased by 10.6% during overnight bed rest, which corresponds to a gain of about 0.9 cm(3) of fluid; 2) the rate of disc volume decrease during the 8-h walking protocol was 0.96 x 10(-3) cm(3)/min; and 3) after 8 h (using our walking/scanning protocol), the disc volume did not decrease to the volume measured at the end of the previous day.
Article
A new rabbit model was developed that produces disc degeneration through the application of controlled and quantified axial mechanical load. 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. 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. 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. 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. 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.
Article
The intervertebral disc is a cartilaginous structure that resembles articular cartilage in its biochemistry, but morphologically it is clearly different. It shows degenerative and ageing changes earlier than does any other connective tissue in the body. It is believed to be important clinically because there is an association of disc degeneration with back pain. Current treatments are predominantly conservative or, less commonly, surgical; in many cases there is no clear diagnosis and therapy is considered inadequate. New developments, such as genetic and biological approaches, may allow better diagnosis and treatments in the future.
Article
To establish whether it is possible to quantitatively characterize the degenerative changes in cartilage that typify arthritis on a sub-150-microm resolution scale using a 3.0 T whole body MR-scanner with a reasonable measurement time. This problem is addressed through diffusion-microimaging investigations on an arthritis model based on the enzymatic destruction of the proteoglycans in cartilage specimen. A 35-mm birdcage resonator made high spatial resolution possible, and diffusion-micro-imaging was achieved with the use of a strong gradient system. Diffusion-weighted and quantitative parameter maps were acquired with 117 x 234 microm2 pixel resolution in less than 9 minutes. Diffusivity profiles and parameter images exhibit an increase in diffusivity in degenerated tissue. In a trypsin-based arthritis model, the spatial localization and quantification of damaged areas have been shown to be possible on a whole body 3.0 T MR system. Measurement times achieved for these high spatial resolution studies make in vivo investigations feasible.
Article
An understanding of developmental biology can provide useful insights into how different tissue-engineered repairs might be designed. During embryogenesis of the intervertebral disk, the cells of the notochord play a critical role in initiating tissue formation, and may be responsible for development of the nucleus pulposus. In some species, including humans, these notochordal cells may eventually be lost, either through apoptosis or terminal differentiation, and are replaced by chondrocyte-like cells. However, there is some evidence that the notochordal cells may persist in at least some humans. This review discusses some of the potential applications of notochordal cells in tissue engineering of the nucleus pulposus.
Article
Intervertebral disc (IVD) pressure measurement is an appropriate method for characterizing spinal loading conditions. However, there is no human or animal model that provides sufficient IVD pressure data. The aim of our study was to establish physiological pressure values in the rabbit lumbar spine and to determine whether temporary external disc compression and distraction were associated with pressure changes. Measurements were done using a microstructure-based fibreoptic sensor. Data were collected in five control rabbits (N, measurement lying prone at segment L3/4 at day 28), five rabbits with 28 days of axial compression (C, measurement at day 28) and three rabbits with 28 days of axial compression and following 28 days of axial distraction (D, measurement at day 56). Disc compression and distraction was verified by disc height in lateral radiographs. The controls (N) showed a level-related range between 0.25 MPa-0.45 MPa. The IVD pressure was highest at level L3/4 (0.42 MPa; range 0.38-0.45) with a decrease in both cranial and caudal adjacent segments. The result for C was a significant decrease in IVD pressure (0.31 MPa) when compared with controls (P=0.009). D showed slightly higher median IVD pressure (0.32 MPa) compared to C, but significantly lower levels when compared with N (P=0.037). Our results indicate a high range of physiological IVD pressure at different levels of the lumbar rabbit spine. Temporary disc compression reduces pressure when compared with controls. These data support the hypothesis that temporary external compression leads to moderate disc degeneration as a result of degradation of water-binding disc matrix or affected active pumping mechanisms of nutrients into the disc. A stabilization of IVD pressure in discs treated with temporary distraction was observed.
Article
The structural integrity of the nucleus pulposus (NP) of intervertebral discs was targeted by enzyme-specific degradations to correlate their effects to the magnetic resonance (MR) signal. To develop quantitative MR imaging as an accurate and noninvasive diagnostic tool to better understand and treat disc degeneration. Quantitative MR analysis has been previously shown to reflect not only the disc matrix composition, but also the structural integrity of the disc matrix. Further work is required to identify the contribution of the structural integrity versus the matrix composition to the MR signal. The bovine coccygeal NPs were injected with either enzyme or buffer, incubated at 37 degrees C as static, unloaded and closed 3-disc segments, and analyzed by a 1.5-Tesla MR scanner to measure MR parameters. Collagenase degradation of the NP significantly decreased the relaxation times, slightly decreased the magnetization transfer ratio, and slightly increased the apparent diffusion coefficient. Targeting the proteoglycan and/or hyaluronan integrity by trypsin and hyaluronidase did not significantly affect the MR parameters, except for an increase in the apparent diffusion coefficient of the disc after trypsin treatment. Our results demonstrate that changes in the structural integrity of matrix proteins can be assessed by quantitative MR.
Article
An animal model of degeneration was used to determine the effects of disc distraction, and was evaluated with magnetic resonance imaging (MRI) as well as gene and protein expression levels. To investigate gene expression and MRI effects of distraction. Disc degeneration can result from hyper-physiologic loading. Distracted discs with degeneration showed histologic signs of tissue recovery. There were 18 rabbits that underwent 28 days of compression (200 N) to induce moderate disc degeneration followed by 28 days of distraction (120 N; attached and loaded distraction device) or sham distraction (attached but unloaded distraction device). Comparison was performed with 56 days of compressed discs without distraction. Quantitative outcome measures were MRI signal intensity and gene expression analysis to determine: messenger ribonucleic acid levels for extracellular matrix genes, including collagen 1, collagen 2, biglycan, decorin, aggrecan, fibromodulin, and osteonectin; and matrix-regulative genes, including matrix metalloproteinase-13, tissue-inhibitor of matrix metalloproteinase-1, and bone morphogenetic protein (BMP)-2. Immunohistology was performed for collagen 2 and BMP-2 to label cells semiquantitatively by staining of the cell-surrounding matrix. A total of 28 days of compression decreased signal intensity. Distraction over the same period reestablished physiologic signal intensity, however, a persistent reduction was found in sham distraction. Distraction resulted in gene expression up-regulation of collagen 1 (5.4-fold), collagen 2 (5.5-fold), biglycan (7.7-fold), and decorin (3.4-fold), while expression of fibromodulin (0.16-fold), tissue-inhibitor of matrix metalloproteinase-1 (0.05-fold), and BMP-2 (0.15-fold) was decreased, as compared with 56 days compression. Distracted discs showed more BMP-2 (19.67 vs. 3.67 in 56 days compression) and collagen 2 (18.67 vs. 11.33 in 56 days compression) positive cells per field. Distraction results in disc rehydration, stimulated extracellular matrix gene expression, and increased numbers of protein-expressing cells.
Article
Whole ovine caudal intervertebral discs with vertebral endplates were cultured under uniaxial diurnal loading for 7 days. To establish and characterize an organ culture system for intervertebral discs, in which disc cells may be "maintained" in their native three-dimensional environment under load. In vitro culturing of entire discs with preserved biologic and structural integrity would be a useful model to study the effects of nutrition and mechanical loading. To maintain endplate permeability, sheep were systemically anticoagulated before death and their caudal vasculature was evacuated with saline postmortem. The first 4 caudal discs were explanted with their adjacent endplates and cultured in bioreactors under uniaxial diurnal loading (0.2 MPa for 8 hours and 0.8 MPa for 16 hours) for 4 or 7 days. Solute transport into the center of the disc was measured after 4 days of culture using a low molecular weight fluorescent marker. Cell viability, glycosaminoglycan synthesis rate, and gene expression profile were measured after 7 days of culture and compared with fresh tissue. Fluorescent images showed that solutes could diffuse into the disc under both static and diurnal loading, but penetration through the endplate increased with diurnal loading. Cell viability and glycosaminoglycan synthesis rates remained unchanged after 7 days of culture. Expression of catabolic genes was significantly up-regulated, whereas anabolic genes tended to be down-regulated after 7 days. With this novel preparation and culturing technique, endplate permeability could be maintained, which allowed culturing of intact disc explants with endplates for up to 7 days.
Rheology of intervertebral disc: an ex vivo study on the effect of loading history, loading magnitude, fatigue loading, and disc degeneration . Spine (Phila Pa
  • Y W Kuo
  • J L Wang
Kuo YW, Wang JL. Rheology of intervertebral disc: an ex vivo study on the effect of loading history, loading magnitude, fatigue loading, and disc degeneration. Spine (Phila Pa 1976) 2010 ; 35 : E743 -52.
Development of a Cost Effective Fluorescent Photographic System for Small Animal and Disc Study
  • T Liu
  • R Wang
  • J Hsiao
Liu T, Wang R, Hsiao J, et al. Development of a Cost Effective Fluorescent Photographic System for Small Animal and Disc Study. Long Beach, CA : Orthopaedic Research Society ; 2011 : 689.
The effi cacy of lumbar extension traction for sagittal alignment in mechanical low back pain: A randomized trial
  • Aa Diab
  • Im Moustafa
Diab AA, Moustafa IM. The effi cacy of lumbar extension traction for sagittal alignment in mechanical low back pain: A randomized trial. J Back Musculoskelet Rehabil 2013 ; 26 : 213 – 20.
  • Kroeber