Clin Biomech (Bristol, Avon). 2010 Aug 23. [Epub ahead of print]

Much is known about intervertebral disc degeneration, but little effort has been made to relate this information to the clinical problem of discogenic back pain, and how it might be treated. The authors re-interpret the scientific literature in order to provide a rationale for physical therapy treatments for discogenic back pain.

Intervertebral discs deteriorate over many years, from the nucleus outwards, to an extent that is influenced by genetic inheritance and metabolite transport. Age-related deterioration can be accelerated by physical disruption, which leads to disc “degeneration” or prolapse. Degeneration most often affects the lower lumbar discs, which are loaded most severely, and it is often painful because nerves in the peripheral anulus or vertebral endplate can be sensitised by inflammatory-like changes arising from contact with blood or displaced nucleus pulposus. Surgically-removed human discs show an active inflammatory process proceeding from the outside-in, and animal studies confirm that effective healing occurs only in the outer anulus and endplate, where cell density and metabolite transport are greatest. Healing of the disc periphery has the potential to relieve discogenic pain, by re-establishing a physical barrier between nucleus pulposus and nerves, and reducing inflammation.

Physical therapies should aim to promote healing in the disc periphery, by stimulating cells, boosting metabolite transport, and preventing adhesions and re-injury. Such an approach has the potential to accelerate pain relief in the disc periphery, even if it fails to reverse age-related degenerative changes in the nucleus.

From: Eur J Pain. 2010 May;14(5):514-22

Widespread pain has negative influence on outcome in low back pain patients. Tender point examination is a standardized examination method to estimate diffuse tenderness. To assess diffuse tenderness by means of a standardized tender point examination and to analyse for associations between the number of tender points and spinal structural changes as well as psycho-social factors.

Patients sick-listed 3-16 weeks due to low back pain with or without sciatica completed a questionnaire and went through a clinical low back examination and tender point examination. Of 326 patients 111 had verified nerve root affection and 215 had non-specific low back pain with or without radiating pain. Disc height reductions were estimated on lateral X-rays.

Multivariate logistic regression analysis showed that more than 8 tender points were strongly negatively associated with disc degeneration, and verified nerve root affection and were positively associated with number of years since first episode of low back pain. Furthermore, more than 8 tender points were positively associated with widespread pain, female sex and bodily distress. With all patients included, bodily distress and the number of tender points were positively associated with the intensity of low back pain, but disc degeneration was only positively associated with low back pain in patients with less than 6 tender points.

The pain in patients with diffuse tenderness was rarely related to disc degeneration or nerve root affection, rather it may be caused by disturbed pain regulation.

BMC Musculoskelet Disord. 2010 Jul 8;11(1):155.

An estimated 80% of the population will suffer from low back pain at some point of their lives. Low back pain is the number one factor limiting activity in patients less that 45 years old, the second most frequent reason for doctor’s visits, and the third most common cause for surgical procedures. In addition to imposing upon patients’ quality of life, low back pain is of significant socioeconomic relevance because it may lead to a temporary loss of productivity, enormous medical and indirect costs, or even permanent disability.

While the management of persistent low back pain remains hotly debated, the traditional approach has been non-surgical treatment with analgesia supplemented by physiotherapy. Given the limited efficacy of these modalities, there are also a number of alternative interventions such as massage, spinal manipulation, exercises, acupuncture, back school and cognitive behavioral therapy. The two most common diseases involving chronic low back pain are discogenic low back pain, responsible for 39% of cases, and disc herniation, accounting for just less than 30% of low back pain incidence. These incidence frequencies are supported by the current data that most closely link the clinical pathology of discogenic low back pain and disc herniation to the anatomical structure of the intervertebral disc. Thus, another treatment option is motorized decompression, a technique designed to lessen pressure on the discs, vertically expand the intervertebral space, and restore disc height. However, systematic reviews to date were unable to find sufficient evidence in the literature to support the use of this modality. A subsequent chart review of 94 patients suggests that motorized non-surgical spinal decompression may be effective in reducing chronic low back pain. Furthermore, preliminary data from a prospective cohort study in patients with chronic low back pain reported a median pain score reduction from 7 to 0 (on a 11-point verbal rating scale) following a 6-week nonsurgical spinal decompression treatment protocol.

The goal of this study was therefore to determine if changes in low back pain, as measured on a verbal rating scale, before and after a 6-week treatment period with motorized non-surgical spinal decompression, correlate with changes in lumbar disc height, as measured on computed tomography scans.

Patients and their medical records were eligible for inclusion if the patient was at least 18 years of age, consented for the 6-week treatment protocol, and presented with chronic low back pain of at least 3 out of 10 on a verbal rating scale and was due to either discogenic low back pain or disc herniation according to a radiological diagnosis using standard medical definitions. Discogenic low back pain is most succinctly defined as a loss of lower back function with pain due to disc degeneration. Degenerative disc disease often emerges when abnormal stresses cause the nucleus gelatinosus to unevenly distribute weight, the annular fibrosis and end plate incur structural damage, and a destructive inflammatory response is triggered to accelerate and perpetuate the degeneration of the disc. A herniated disc (synonymous with a protruding or bulging disc) arises when the intervertebral disc degenerates and is weakened to such an extent that cartilage is pushed into the space containing the spinal cord or a nerve root and causes pain.

Initial decompression force was adjusted to patient tolerance, starting at 4.54 kg (10 lbs) less than half their body weight. If a patient described the decompression pull as strong or painful, this distraction force was decreased by 10%–25%. In subsequent treatment sessions, the distraction force was increased as tolerated to final levels of 4.54 kg to 9.07 kg (10 to 20 lbs) more than half their body weight. Patients continued to use analgesics prescribed by their physicians before enrollment, but were allowed to use additional non-steroidal pain medication should their pain increase temporarily and permitted to discontinue pain medication as needed. During the routine physical examination prior to beginning the non-surgical spinal decompression treatment session, at the first and final visits maximal pain was evaluated during a flexion-extension range of motion exam with the question How strong is your pain on a scale of 0-10 with 0 being no pain and 10 as bad as it could be?

During a two year period only 30 of those patients fulfilled the per protocol inclusion and exclusion criteria for the analysis. The 30 participants consisted of 21 female and 9 male patients with lumbar disc herniation. They had a mean age of 65 (± 15) years, a body mass index of 29 (± 5) kg/m2, and an average duration of low back pain of 12.5 (± 19) weeks with a score of 6.3 (± 2.2) on the VRS. All 30 patients had a disc prolapse and the majority (n=25) also had degenerative disc disease. The maximum force during the first treatment was on average 33.9 (± 6.8) kg and gradually increased during subsequent treatment visits to 52.4 (± 7.6) kg. Low back pain decreased from 6.2 (± 2.2) to 1.6 (± 2.3) and disc height increased from 7.5 (± 1.7) to 8.8 (± 1.7) mm. There was a statistically significant correlation between the increase in disc height and a reduction in pain, with a 1 mm increase in disc height being associated with a reduction of 1.86 on the 11-point verbal rating scale. No adverse events were reported during the treatment period.

In this cohort study we extracted data from 30 patients with discogenic low back pain and found an average reduction in pain from 6.2 to 1.6 after non-surgical spinal decompression. This level of pain relief is consistent with two previous studies using DRX9000 to decrease chronic low back pain. However, here we systematically investigated the change in disc height before and after the treatment, and were able to show that increases in disc height correlated with increased pain relief. A mechanical explanation for this correlation might be that spinal decompression reduces the pressure on the discs. This relief of stress would simultaneously promote regeneration of diseased and compressed discs and increase lumbar disc height, with the latter reducing load on the facet joints.

It is well recognized that continuous pressure on vertebral discs decreases their height. Humans are taller in the morning after the discs decompress while the body is supine overnight and shorter in the evening after the discs have borne weight during daily activity. Interestingly, this effect occurs quite rapidly so that the majority of height-loss in a day occurs within the first hour of arising. Therefore, all CT scans analyzed in this study were performed at least one hour after the subject got out of bed. The first CT scan was performed within two months before the initiation of the treatment and at least one day after or the day immediately before the final treatment session.

A clear diagnosis cannot be made in approximately 80% of cases of low back pain, and imaging techniques can only offer a partial solution to the problem of making a causal diagnosis of low back pain. One might argue that a CT scan is not as sensitive a measure of disc height as an MRI scan because it images soft tissues poorly and cannot examine internal disc morphology. However, because the primary objective was to establish an observable correlation between disc height increase and decreased low back pain, a CT scan permitting examination of the outline of the intervertebral discs at high resolution provided sufficient measurable evidence.

It has been demonstrated that low back pain can lead to muscle spasms that could directly perpetuate pain, or induce pain within the disc as nerve fibers have been described to grow into the inner part of the annulus fibrosus or nucleus pulposus. It is hypothesized that the pain-spasm-pain cycle is perpetuated by further reduction in disc height, which also simultaneously aggravates the facet joint. In either case, dampened pressure on the disc should facilitate the regeneration of the disc and assuage facet joint stress. In fact, it has been described that non-surgical spinal decompression mechanically creates negative intradiscal pressures, and it is speculated that this supports disc regeneration, though this remains controversial.

Pain measurement relies first and foremost on patient report. Taking into account the subjectivity inherent in this process, it was noted that a cut-off point, or rather the change in pain score necessary for detecting a clinically important difference in an individual patient, was needed to identify responders and non-responders to analgesia. Farrar et al reported that on average a reduction in pain intensity of at least 2 points on the NRS serves as a clinically significant change. Using this standard, in this cohort study this intervention had a success rate of over 75% (pain decreased by more than 2 out of 11 in 23 out of 30 patients). In this analysis, each millimeter of increase in disc height was associated with pain relief of roughly 2 points on the scale, a clinically important difference according to the aforementioned report.

However, not all patients responded equally. This raises the question of inter-individual variability and might be addressed by taking into account the heterogeneity of lumbar spine muscle strength acting as a counterforce to the external distraction. Even though the DRX9000 machine has an integrated sensor to detect counterforces, non-surgical spinal decompression can only work if lumbar spine muscles are relaxed. Another reason for different inter-individual response rates could be the age of the patients. However, in sub-analyses the authors did not find a correlation between age and treatment success. With regards to the elderly cohort of patients analyzed in this retrospective study, it is possible that a younger patient population might respond differently to the non-surgical spinal decompression treatment given that they would generally have less disc degeneration, be more active, and have less co-morbidity than the elderly population studied here. Yet this is a hypothesis that remains to be tested in a future prospective study investigating therapies to alleviate low back pain in younger patients. While the authors largely believe the range of muscle tone during nonsurgical spinal decompression to be the main reason for different treatment effects, other reasons for variability could be differing stages and degrees of degenerative disc disease, an assortment of activity levels, and a wide spectrum of concomitant treatments ranging from chiropractic interventions and pain medication cocktails.

Patients with chronic discogenic low back pain are usually on a wide range of analgesics, and pain and analgesic consumption is generally positively correlated. As a result, interventions that reduce pain typically lead to a reduced consumption of analgesics and thus counteract the treatment effect of the intervention (suppressor effect). The fact that a significant reduction of pain was observed even though analgesics were not controlled for corroborates the observation of pain relief through non-surgical spinal decompression.

In this study of non-surgical spinal decompression for chronic discogenic low back pain the authors were able to demonstrate an association between the restoration of disc height and pain relief. The correlation of these variables suggests that pain reduction may be mediated, at least in part, through a restoration of disc height. These results call for a randomized placebo-controlled trial to substantiate the efficacy and elucidate the mechanism of this promising treatment modality.

From: Spine J. 2010 Apr;10(4):297-305. Epub 2010 Feb 26

Sitting is associated with loss of the lumbar lordosis, intervertebral disc compression, and height loss, possibly increasing the risk of lower back pain. With a trend toward more sitting jobs worldwide, practical strategies for preventing lumbar flattening and potentially associated low back pain are important. The purpose of this study was to determine the feasibility of using upright magnetic resonance imaging (MRI) and stadiometry to measure changes in height and configuration of the lumbar spine before and after normal sitting and a sitting unloading exercise intervention.

This is a hospital-based pilot study involving pre-post assessments in a single group. The sample comprises six asymptomatic hospital employees involved in either general patient care or research writing/data collection. The outcome measures were lumbar total midsagittal cross-sectional intervertebral disc area, vertical height, lordotic angle derived from digitized MRI examinations, and seated body height measured directly with a stadiometer. Midsagittal MRI scans were performed before sitting, after 15 minutes of relaxed sitting (“postsitting”), immediately after seated unloading exercises, and approximately 7 minutes after exercise. Subsequently, seated stadiometry assessments were performed after 10 minutes of supine recumbency, 15 minutes of relaxed sitting, and every 10 seconds after seated unloading exercises until three consecutive height measurements were identical. Digitized midsagittal images were used to derive MRI based outcome measures.

After 15 minutes of sitting, mean total intervertebral disc area, lordotic angle, and vertical height of the lumbar spine decreased 18.6 mm(2), 6.2 degrees , and 12.5 mm, respectively, whereas after seated unloading exercises, these parameters increased by 87.9 mm(2), 5.0 degrees , and 21.9 mm, respectively. Similarly, mean seated height on stadiometry decreased by 6.9 mm after 15 minutes of sitting and subsequently increased by 5.7 mm after unloading exercises.

Seated upright MRI and stadiometry, as performed in this study, appear to be feasible methods for detecting compressive and decompressive spinal changes associated with normal sitting and, alternately, seated unloading exercises. Larger studies are encouraged to determine normative values of our study measurements and to determine if morphological changes induced by seated unloading predict treatment response and/or reductions in the incidence of sitting related low back pain.

These findings confirm an earlier study on the unloading sitting exercise, J Bodyw Mov Ther. 2010 Apr;14(2):119-26. Epub 2008 Jul 31. Preliminary investigation into a seated unloading movement strategy for the lumbar spine: a pilot study.

This study was a preliminary investigation into a seated unloading movement strategy for the lumbar spine using the upper extremities. With the economic burden of low back pain estimated in the billions worldwide, and also with a trend towards more jobs related to sitting, a simple distraction exercise coined chair-care is presented. An attempt to objectify using stadiometry was used to measure standing height changes after 15 min of sitting and after the exercise. The results showed significant standing height gains post-exercise when compared to post-sitting and initial standing (2.4 and 2.7 mm, respectively). No significant standing height changes were seen after 15 min of sitting. It is therefore likely that this simple seated exercise creates standing height gains of the spine. Proposed mechanisms are discussed with an emphasis on spinal hydraulics and intervertebral disc nutrition.

From: Spine (Phila Pa 1976). 2010 May 25. [Epub ahead of print]

An in vivo rat-tail model was adopted to study the structural changes of degenerated intervertebral disc after different traction protocols to investigate the effects of traction with different modes and magnitudes on disc with simulated degeneration.

Traction has been commonly used in clinical practice for treating low back pain. Its effects on disc with degeneration have not been fully investigated. Forty-seven mature rats were used. Continuous static compression of 11 N was applied to the rat caudal 8-9 disc for 2 weeks to simulate disc degeneration. Tractions with different modes (static or intermittent) and magnitudes (1.4 N or 4.2 N) were applied to the degenerated disc for 3 weeks. The disc height was quantified in vivo on days 4, 18, and 39. The treated discs were then harvested for morphologic analysis.

Significant decrease in disc height with degenerative morphologic changes was observed after the application of the static compression. The changes in disc height after the application of traction were found to be magnitude dependent. Continuous decrease in disc height was observed after 4.2-N traction, whereas the disc height maintained after traction of 1.4 N. However, no obvious morphologic change was found in comparison with the degenerated discs without traction.

Although traction was not demonstrated to have restored disc with degeneration, traction with relatively low magnitude was found to have significant beneficial effect in maintaining disc height of degenerated disc, and it might be a potential intervention to slow down the process of degeneration. Future studies of the effects of low-magnitude traction on degenerated disc are recommended.

From: Spine (Phila Pa 1976). 2010 Mar 1;35(5):531-6.

Back pain is one of the most common musculoskeletal complaints of the elderly, with a point prevalence of 26.9% in the Netherlands. Van Tulder et al performed a systematic review and reported that lumbar disc degeneration could be a possible risk factor for back pain in adults. However, the review reported that the methodologic quality of most of these studies was low and the studies were difficult to compare due to difference in gender frequencies, age groups, settings, radiographic grading systems, and definitions for lumbar disc degeneration.

Lumbar disc degeneration is characterized radiologic by the presence of osteophytes, endplate sclerosis, and disc space narrowing. In 1993, Lane et al presented a reliable grading system for these individual radiographic features. In a recent review, this grading system was recommended for use in epidemiologic studies. There have been a number of recent studies that have used the classification of the individual radiographic features of disc degeneration defined by Lane et al. One of these studies described the occurrence of these separate features and their relationship with back pain in the open population, but only in a limited sample.

However, it is still unknown how to combine the individual radiographic features and how to define a clinically relevant definition for lumbar disc degeneration. Currently there is no consensus about whether the lumbosacral disc should be scored. Some studies have included the lumbosacral level in their definition of lumbar disc degeneration, while others have not. Currently within the literature, there have been no studies that have explored different definitions of lumbar disc degeneration and their association with low back pain within one study sample.

The purpose of this study was to explore the association of the different individual radiographic features, including osteophytes and disc space narrowing, with self-reported low back pain. Different definitions of lumbar disc degeneration with self-reported low back pain and disability were considered in a large open population sample. Furthermore, in order to disentangle the discrepancies in reported strength of the associations, the authors characterized the frequency of the different individual radiographic features of lumbar disc degeneration and definitions of lumbar disc degeneration, as well as their association with low back pain status, by age, gender, and vertebral level.

The authors are the first to report in one paper, multiple lumbar disc degeneration definitions and their associations with low back pain, for the separate genders and discreet age groups. In this study, disc space narrowing appeared to be more strongly associated with low back pain than osteophytes, especially in men. Disc space narrowing at 2 or more levels appeared more strongly associated with low back pain than disc space narrowing at only 1 level. The strength of the associations increased with chronic low back pain. The majority of the associations were strengthened by excluding level L5–S1.

The most frequently observed radiographic feature of lumbar disc degeneration was osteophytes, with greater frequency in men than in women. Narrowing, however, was more common in women than in men and was also shown to be more frequent at the lower disc levels. Both individual radiographic features increased in frequency with age.

Data from many studies suggest an association with lumbar disc degeneration and low back pain. The authors are not aware of data from population-based samples that have investigated the association of different definitions of lumbar disc degeneration with self-reported low back pain. MacGregor et al performed a study, using MRI scans to assess risk factors associated with severe back pain. They investigated a number of features including; disc height, signal change, disc bulge and anterior osteophytes, and made a sum score for all features together. This sum was associated with severe back pain. However, they did not state which features had the highest predictive capability. Some studies suggest an association between osteophytes and low back pain and some studies suggest an association between disc space narrowing and low back pain. The data from this study confirms the association between low back pain and disc space narrowing. In addition, the data suggest an association with osteophytes, only when a more specific definition (osteophytes) is used. However, when osteophytes and disc space narrowing were both included in the model, there was no association with osteophytes anymore. Therefore osteophytes do not have an independent association with low back pain and seem therefore an inferior derivate from disc space narrowing.

Some studies suggest that the strength of the association between low back pain and disc space narrowing grows with increasing severity of disc space narrowing. Data from this study confirm this, but only when L5–S1 is excluded. Further, the data indicate that the association between low back pain and disc space narrowing increases when a greater number of levels are affected.

The explanation for the stronger association between low back pain and disc space narrowing compared with the presence of osteophytes is unknown. It is possible that the reduction of space between the vertebrae as a consequence of the degenerative disc is more likely to lead to increased pressure on facet joints and spinal ligaments.

The explanation for the stronger association between back pain and disc space in men compared with the association in women is also unknown. It is possible that even though women reported low back pain more often, only a small proportion of the complaints are due to lumbar disc degeneration, whereas other factors determine the feeling of pain. Men and women could also report pain differently therefore effecting the association between back pain, disc space narrowing and gender. Cecchi et al showed that women presented with significantly more severe pain than men.

A possible explanation for the stronger association between low back pain and disc space narrowing, excluding level L5–S1, is the possible overrating of the narrowing grade of the lumbosacral disc. The height of the lumbosacral disc is difficult to score due to its narrowed height relative to disc L4–L5. The lumbosacral disc is also different in appearances among different individuals, independently of disease. Therefore, by using the lumbar disc definition “narrowing 1 to 4,” the inconsistency of the grading scores at this level is ruled out. Furthermore, some differences in the reported associations in the prior studies can be explained by the stratified results. Possible explanations for relatively low odds ratios previously reported could be due to the use of a young age group, the use of women only and scoring of the lumbosacral level.

Data from this study confirms the findings from recent population based radiographic surveys showing a greater frequency and severity of osteophytes in men than in women. A possible explanation for the greater frequency in men is the higher BMD in men. However, after including BMD in the model, although less explicit, men still show a greater frequency and severity of osteophytes.

Data from this study suggest a greater frequency and severity of narrowing in women than in men and confirms that the prevalence of osteophytes and disc space narrowing increases with age in both men and women.

The authors defined chronic low back pain to be present when the duration of the low back pain was more than 1 year. In this way the definition chronic low back pain included long lasting chronic complaints with long lasting impact on ones life. When they defined chronic low back pain to be present when the duration of the low back pain was more than 6 months, the OR of the associations diminished.

From this data, a useful case definition for lumbar disc degeneration can be deduced; specifically disc space narrowing at 2 or more levels from L1/2 to L4–L5. This definition shows the strongest relationship with low back pain and represents a more generalized form of lumbar disc degeneration. As a result it might be a promising clinically relevant phenotype in genetic and epidemiologic lumbar disc degeneration research.

The data provides evidence for a moderate association between disc space narrowing and low back pain. This association is only slightly less than the association of pain and radiologic knee osteoarthritis and even slightly more than the association of pain and radiologic hand osteoarthritis in the same population sample.

The most important aspect of the data are that disc space narrowing at 2 or more levels is even more related to chronic low back pain. The ability of lumbar disc degeneration in predicting low back pain at the follow-up period was unfortunately not possible to investigate, as no questions about low back pain specifically were asked at the follow-up visit.

The data provides evidence for an association between disc space narrowing and low back pain especially in men, with the association increasing, with increasing numbers of affected intervertebral disc spaces. The data highlights the frequent occurrence of individual radiographic features, as well as the increased frequency in age, of the individual radiographic features of lumbar disc degeneration in population samples of men and women.

From: Chin Med J (Engl). 2010 Jan;123(2):239-43

Low back pain is a common public health problem in western industrialized societies and the world as well. Studies indicate that the prevalence rate ranges from 12% to 35%, with around 10% of patients becoming chronically disabled. It also places an enormous economic burden on society. Although the exact cause of low back pain has yet to be defined, intervertebral disc degeneration is considered a major source of it. Since patients with degenerative discs are often asymptomatic, the mechanisms of it are still unclear.

The intervertebral disc lies between the vertebral bodies and links them together. It provides reversible resistance to compressive, rotational, and tensile loads applied to the vertebral column and it also allows the spine to bending, flexion, and torsion. Three major components ensure the properties of the disc: nucleus pulposus, anulus fibrosus, and cartilaginous endplate. Nucleus pulposus represents a centrally located gelatinous homogenous mass (in juvenile discs), anulus fibrosus consists of concentrically organized layers of collagen fibrils, and endplate separates the nucleus pulposus and anulus fibrosus from the adjacent vertebral bone. Any disturbance of the integrity and interplay of one of the three structures can result in a compromised function of the intervertebral disc.

The normal human intervertebral disc in adulthood consists of a large amount of extracellular matrix interspersed by a small number of cells that make up approximately 1% of the total volume. Cells of the disc are made up of at least two phenotypically distinct populations and they are morphologically different; those in the anulus fibrosus and cartilaginous endplate are more elongated and fibroblast-like compared with those of the nucleus pulposus, which are more rounded or oval and chondrocyte-like, sometimes with a capsule around them. These two kinds of cells behave differently, nucleus pulposus cells generally synthesize only type-II collagen in alginate beads, whereas anulus fibrosus cells produce both type-I and type-II collagen.

The cells within the disc synthesize the matrix and maintain and repair it. The disc matrix consists of an elaborate framework of macromolecules filled with water. The principal macromolecules are collagen and proteoglycans; the collagenous fibrils are embedded in a gel of proteoglycans and water.

In humans, the superficial layer of the anulus fibrosus of the intervertebral disc contains blood vessels for approximately three years after birth. However, the intervertebral disc becomes the largest avascular tissue without penetrating blood vessels thereafter. But like other types of cells, the cells of the disc require nutrients, such as glucose and oxygen to remain alive.

The upper and middle parts of the lumbar spine (L1–L4) receive their blood supply from four pairs of lumbar arteries, whereas the lower part of the spine is supplied by the lowest pair of lumbar arteries, the medial sacral artery and the iliolumbar arteries, of which the two lowest pairs of lumbar arteries and the middle sacral artery originate from the abdominal aorta at the aortic bifurcation. The first to fourth lumbar arteries leave the aorta in front of the corresponding vertebral body, and the middle sacral artery in the bifurcation in front of the fourth lumbar vertebra or L4-L5 intervertebral space. But the blood supply to the vertebrae is not constant in everyone, many variations may exist. According to a recent study, the authors collected 187 cadavers (132 men, 55 women) to figure out the accurate site of the abdominal aortic bifurcation, and found that the abdominal aorta descended and bifurcated into two common iliac arteries at the level of L4 vertebra in 131 cases (70.1%), at the fourth lumbar intervertebral disc in 23 cases (12.3%), and at the level of L5 vertebra in 33 cases (17.6%). The disc is supplied by capillaries that are fed from these arteries and drain into the subchondral venous network or into the veins of the marrow spaces of the vertebral bodies. These capillaries have muscarinic receptors that regulate blood flow in response to external signals.

Studies show that the intervertebral disc receives nutrients through two routes: the anular route, through which the disc receives blood directly from the vascular plexus surrounding it, and the vertebral route, which supplies blood from the vertebral body through the vertebral endplate. Different kinds of nutrients may be transported to the disc through different routes. Some evidence is provided that anions and cations are transported mainly through the anular route, whereas noncharged particles are conveyed equally through both routes. While some other studies reported that the vertebral route was the main route for the transportation of noncharged particles. Difference between these two studies may arise from differences in experimental methods and processes through which theoretic equations are deduced. The exact route remains to be clarified in the future.

Although the problem of degenerative disc disease has been approached from many sides, there is no exact interpretation on what is “disc degeneration”, until recently, Adams et al proposed that the process of disc degeneration was an aberrant, cell-mediated response to progressive structural failure and a degenerated disc was one with structural failure combined with accelerated or advanced signs of aging.

One of the primary causes of disc degeneration is thought to be failure of the nutrient supply to disc cells. The activity of disc cells is very sensitive to change of extracellular oxygen and pH, with matrix synthesis rates falling steeply at acidic pH and at low oxygen concentrations, and the cells do not survive prolonged exposure to low pH or glucose concentrations. A fall in nutrient supply may lead to a lowering of oxygen tension, which results in the disc cells undergoing anaerobic metabolism with the more production of lactic acid. As removal of waste products from the large avascular mature disc is difficult, lactic acid accumulation can occur, and then cause an acidic pH environment. The nutrient supply to the disc cells can be disturbed at several points. Factors that affect the blood supply to the vertebral body such as atherosclerosis, sickle cell anemia, Caisson disease, and Gaucher’s disease all appear to lead to decrease in the nutrient supply to the disc and increase in disc degeneration.

Since blood supply of the intervertebral disc is mostly dependent on that of the vertebral body, reduction of blood supply to the vertebral body may indicate the similar condition of the intervertebral disc. In a recent study, the researchers recruited 25 patients and assessed two vertebral bodies (L1 or L3) in each patient. After controlling variables that might affect blood perfusion, they found that the insufficient lumbar vertebral marrow perfusion correlated well with intervertebral disc degeneration through the test of dynamic contrast- enhanced MRI and blood perfusion was 14% less in the vertebral body marrow between two degenerated disks than that between two normal discs, which meant that the insufficient vertebral blood supply might be correlated with degeneration of the intervertebral disc.

Atherosclerosis of arteries supplying the lumbar region has been suggested as a mechanism leading to intervertebral disc degeneration. Atheromatous lesions in the wall of the abdominal aorta usually develops at the ostia of branching arteries and the bifurcation, and may obliterate orifices of lumbar and middle sacral arteries. The plaques prevent the blood supply in the lumbar arteries, resulting in ischemia and scarce blood supply to the disc area and inadequate nutrition of the discs, thus render the discs more vulnerable to mechanical stress. Fifty-one Finnish patients ranging from 35 to 70 years of age (mean age, 56 years) with long-term lower back pain were tested MR aortography. The prevalence of occluded arteries was 2.5 times more than in subjects of corresponding age group in a Finnish necropsy material. More than half of the patients had significant disc degeneration. Association analysis found that disc degeneration was associated with occluded lumbar/ middle sacral arteries.

A 25-year follow-up study showed that at the baseline examination, aortic calcification, a marker for advanced atherosclerosis, was significantly associated with general disc degeneration; in longitudinal, aortic calcifications predicted disc deterioration, and calcific lesions in the upper part of the abdominal aorta predicted disc deterioration at any lumbar level, whereas calcific lesions in the lower part of the aorta, the reason of which might be that calcified plaques in the upper abdominal aorta, usually indicated more extensive atherosclerosis than lesions limited to the lower part of the aorta. Furthermore, subjects whose aortic calcifications developed between the examinations had disc deterioration twice as frequently as those in whom aortic calcifications did not develop, and individuals with severe posterior aortic calcification in front of any lumbar segment were more likely than others to report back pain during adult life. So the researchers concluded that aortic calcification, a marker for advanced atherosclerosis, increased a person’s risk for the development of disc degeneration and was associated with the occurrence of back pain. Posterior calcification may be a sign of atheromatous obliteration of a feeding artery or arteries of the lumbar spine, which leads to impaired nutrition of the lumbar spine. The intervertebral disc, with its precarious nutrient supply, may be one of the first structures to suffer from insufficient nutrient supply, thus linking aortic calcification with disc degeneration.

The results of another study proved that more than half of the patients with low back pain had atherosclerotic calcifications visible on CT scans, whereas only 21% of the age-matched patients without low back pain were found to have aortic calcifications. Nearly half of the patients with low back pain who were 50 years of age or less had aortic calcifications, whereas less than 10% of the 36 control patients had aortic calcifications. And the quantity of calcified plaques in the aorta was found to be greater in the group of patients with low back pain than in the control group, especially in the group whose patients aged less than 50 years. But they claimed no correlation between the amount of calcifications and the degree of disc degeneration assessed by CT discography, which is not accord with the results of Kauppila et al. Reasons may be due to the indirect assessment of the severity of arterial disease in the arteries supplying lumbar spine in this study, so the arterial flow to the disc area may thus also be different in subjects even with equal quantities of plaques. Furthermore, the degrees of disc degeneration were not comparable between the two studies.

Smoking is a separate risk factor common to both low back diseases and arterial diseases. The most widely accepted explanation for the association between smoking and disc degeneration is malnutrition of spinal disc cells by carboxy-hemoglobin-induced anoxia or vascular disease. Cigarette smokers may undergo cell apoptosis, faulty synthesis of disc macromolecules, and an imbalance between disc matrix proteinases and their inhibitors, which can induce the pathogenesis of disc degeneration. There is also some evidence that disc degeneration of cigarette smokers is of more severe degree than that of non-smokers. Other studies still indicated that passive cigarette smoking caused changes in gene expression, such as the downregulation of collagen genes, which precedes the histologic changes in the intervertebral discs. A 16-year follow-up research was carried out on 98 407 female nurses aged 30–55 years to clarify smoking as a cardiovascular risk factor for physician-diagnosed lumbar disc herniation. Besides adjusting for age, body mass index (BMI), vigorous or moderate exercise and other variables, compared with never smokers, the incidence of herniation for past smokers was significantly higher, for current smokers the incidence increased with the number of cigarettes smoked per day, and a decrease occurred after cessation of smoking. Another 5-year follow-up longitudinal study using digital MRI on 134 male monozygotic twins (35–69 years of age) showed that smoking might predict more disc height reduction, which meant more severe progression of disc degeneration.

An animal study provided direct evidence of the effect of smoking on the degeneration of discs. Rats subjected to passive smoking for 8 weeks exhibited great histological changes in the intervertebral discs, such as cracks, tears, misalignment of the annulus fibrosus, and increased fibrous tissue in the nucleus pulposus. The IL-1 beta level was higher in the smoking group than that in the non-smoking one. In addition, after stopping passive smoking, progression of degeneration ceased, and the matrix of the nucleus pulposus and annulus fibrosus showed increased fibrous connective tissue and proteoglycan. In vitro study showed that the chondrocytes in the disordered annulus fibrosus layer tended to grow larger and attain a rounder form than normal chondrocytes. So tobacco smoke inhalation increased decomposition of chondrocyte activity and local production release of inflammatory cytokines, which may be the indication or cause of intervertebral disc degeneration.

Nicotine, the active ingredient of tobacco, acts pharmacologically on the cardiovascular system and results in contraction of blood vessels, tachycardia, and a rise in arterial blood pressure. Rabbits treated with nicotine for 8 weeks underwent a significant decrease in the number of vascular buds in the vicinity of the vertebral endplate, decrease in the number of red blood cells and enlargement of endothelial cells together with narrowing of the vascular lumen, which indicated that nicotine had deleterious effect on the intervertebral disc in vivo. Bovine chondrocytic intervertebral disc cells were seeded in alginate with or without freebase nicotine at concentrations found in the serum of smokers (25–300 nmol/L). DNA, glycosaminoglycans (GAG), and hydroxyproline were tested as the extent of disc degeneration. At lower doses, significant increase in the above parameters was found in the early stage, while at higher doses, there was a significant dose-dependent decrease in these parameters compared with controls. Furthermore, other degenerative changes were revealed in the higher nicotine groups, such as reduced cell proliferation, disrupted cell architecture, disintegration of cells and extracellular matrix, and the presence of type I collagen in the extracellular matrix. So nicotine has an overall detrimental effect on disc cells cultured in vitro, and there was significant inhibition of cell proliferation and extracellular matrix synthesis.

According to the study of Kauppila et al, the incidence of disc degeneration, advanced atherosclerotic manifestations, and stenosis of the ostia of the lumbar and middle sacral arteries all increased with age. After partial rank correlation analysis, keeping the effect of age constant, there was still a statistically significant association between the grade of disc degeneration and stenosis of the ostia of the arteries supplying the disc. The association was stronger at upper lumbar levels than at lower ones. They believed that stenosis of the ostia of segmental arteries played a part in lumbar disc degeneration. In a study of middle-aged Finnish males, Logistic regression analysis was used to evaluate the association between arterial stenosis in two-dimensional time-of-flight magnetic resonance angiography (2D TOF-MRA) and low back pain. In 43% subjects, all arteries were normal, whereas 57% had at least one stenosed artery. The left L4 artery was most often affected. The degree of arterial stenosis was associated with intensity, duration and frequency of low back pain. A cross-sectional observational study was carried out on 81 (66 women and 15 men) subjects. On CT scan, a positive correlation between degree of aortic wall calcification and disc degeneration score was found. Epidemiological studies showed that aging, high BMI, high LDLc, the risk factors of atherosclerosis correlated significantly with intervertebral disc degeneration.

The disc is a large and avascular tissue, and disc cells depend on blood vessels at their margins to supply nutrient and remove metabolic waste. So disturbances of blood supply may play an important role in the degeneration of intervertebral disc. Many studies have shown strong association between atherosclerosis and intervertebral disc degeneration. Furthermore, cardiovascular diseases and intervertebral disc degeneration share some similar risk factors, especially smoking as a separate one.

Source: Association between intervertebral disc degeneration and disturbances of blood supply to the vertebrae.

From: Genet Test Mol Biomarkers. 2010 Mar 31. [Epub ahead of print]

The aim of this study was to investigate the association between the polymorphisms of vitamin D receptor and aggrecan genes and degenerative disc disease in young Turkish patients. Aggrecan and vitamin D receptor proteins are the main components of bone and cartilage. In our study, the polymorphisms of vitamin D receptor and aggrecan genes were investigated in a total of 300 individuals regarding disc degeneration and herniation.

An association was found in the patients having vitamin D receptor gene TT, Tt, FF, and Ff genotypes with the protrusion type of disc herniation, whereas the patients having tt and ff genotypes were associated with extrusion/sequestration types of the disease. Also, an association was observed between TT and FF genotypes of vitamin D receptor gene and mild forms of disc degeneration; and tt, ff, and Ff genotypes and severe forms of the disease. There was also an association between shorter, normal, and longer alleles of the aggrecan gene and a protrusion type of disc herniation. An association was found between short alleles and multilevel and severe disc degeneration, as well as normal and long alleles and mild disc degeneration. This study revealed that the polymorphisms of vitamin D receptor and aggrecan genes are associated with disc degeneration and herniation.

The Journal of Bone and Joint Surgery (American) 84:2022-2028 (2002)
“This study revealed that the Tt allele of the vitamin-D receptor gene was more frequently associated with multilevel and severe disc degeneration and disc herniation than was the TT allele, pointing to an increased risk of disc disease at an early age in subjects with the Tt allele in the vitamin-D receptor gene.”

Spine: 1 December 1999 – Volume 24 – Issue 23 – p 2456
“The current study showed that multilevel and severe disc degeneration was present in the participants with shorter variable numbers of tandem repeat length of the aggrecan gene. This suggests that subjects with shorter variable numbers of tandem repeat length of the aggrecan gene have a risk of having multilevel disc degeneration develop at an early age.”

From: Clinical Biochemistry Volume 42, Issue 15, October 2009, Pages 1504-1511

This study was conducted to investigate the expression of cytokines and growth factors in disc specimens obtained from patients with herniated nucleus pulposus and degenerated disc disease. MRI and Western blot analyses were performed to evaluate the levels of disc degeneration and the expression levels of cytokines and growth factors.

The levels of TNF-alpha and IL-8 were significantly greater in the degenerated disc disease group than in the herniated nucleus pulposus group, but no statistical differences were observed in the expression of IL-1beta, IL-6 and IL-12 between the herniated nucleus pulposus and degenerated disc disease groups. In addition, the expression of TGF beta, VEGF and NGF was significantly higher in the degenerated disc disease group than in the herniated nucleus pulposus group.

The greater levels of cytokine and growth factor expression in the degenerated disc disease group than in the herniated nucleus pulposus explain why discogenic patients usually have more severe back pain than patients with herniated discs.

Figure Descriptions:

1) Fig. 1. Western blot analysis and relative intensities of the expression of cytokines and TNF-alpha. (A) Western blots of (1) IL-1 β (2) IL-6 (3) IL-8 (4) IL-12 (5) TNF-α and (6) tubulin. Disc tissue proteins (30 μg) of herniated nucleus pulposus and degenerated disc disease patients were loaded in each lane. (B) the quantities represented by gel bands are expressed as intensities relative to tubulin. (1) IL-1 β (2) IL-6 (3) IL-8 (4) IL-12 (5) TNF-α. The data shown represent the means ± SD (n = 12 and 10 for herniated nucleus pulposus and degenerated disc disease, respectively).

2) Fig. 2. Western blot analysis and relative intensities of the expression of growth factors. (A) Western blots of (1) bFGF (2) NGF (3) PDGF (4) TGF-β (5) VEGF and (6) tubulin. Disc tissue proteins (30 μg) from herniated nucleus pulposus and degenerated disc disease patients were loaded in each lane. (B) quantities represented by gel bands are expressed as intensities relative to tubulin. (1) bFGF (2) NGF (3) PDGF (4) TGF-β (5) VEGF. Data represent the means ± SD (n = 12 and 10 for herniated nucleus pulposus and degenerated disc disease, respectively).

3) Fig. 3. Association of the expression of cytokines and growth factors with MRI grade. (A) association of the expression of cytokines and MRI grades 3 and 4 in the herniated nucleus pulposus group, (B) association of the expression of cytokines and MRI grades 4 and 5 in the degenerated disc disease group, (C) association of the expression of growth factors and MRI grades 3 and 4 in the herniated nucleus pulposus group, (D) association of the expression of growth factors and MRI grades 4 and 5 in the degenerated disc disease group.

From: Yonsei Med J. 2009 Oct 31;50(5):624-9

Facet tropism is defined as asymmetry in both the facet joint angles of the lumbar and lumbosacral regions. For many years, the effect of facet tropism on the development of intervertebral disc degeneration has been debated. However, the specific details regarding the effects of facet tropism on the development of degenerative disc disease remains as the subject of debate. Most of the previous facet tropism studies have focused on the relationship between facet tropism and lumbar disc herniation.

The role of facet tropism in the pathogenesis of lumbar degenerative disc disease is not fully understood Currently, controversy exists surrounding the question of whether or not any significant relationship exists between facet tropism and the development of disc or facet joint degeneration. Additionally, the relationship between facet tropism and degenerative spondylolisthesis and translational segmental motion is highly controversial.

In the current study, the authors attempted to evaluate the effect of facet tropism on disc and facet joint degeneration. Additionally, the relationship between facet tropism and changes in translational segmental motion was investigated.

Facet tropism is defined as asymmetry between the left and right facet joint angles of the lumbar spine. Asymmetry in the orientation of the zygapophyseal joint surfaces is not uncommon, with estimates of its occurrence at 10-70.5% of the population. Our study revealed an incidence of facet tropism in 35% of the spinal units which were taken into consideration. Facet tropism is most common at L5-S1, followed by L4-L5.

The criteria for determining facet tropism have varied greatly, although the actual definition of facet tropism is asymmetry between the right and left facet joints. In the lumbar spine, the majority of facet joints vary by less than 7° in orientation between the two sides. Noren et al. defined facet asymmetry as a bilateral angle difference greater than 5°. In other biomechanical studies, facet asymmetry was defined as a difference in facet angles greater than 1-10° or one SD. Grogan, et al. divided facet joint tropism into three distinct classifications. When the orientation differed from one side to another by more than 7°, the facet joints at that level were defined as having tropism. Moderate tropism was defined as a difference of 7° to 15° between the orientation of the joints (one SD from the mean difference) and severe tropism was defined as a difference of more than 15° (two SDs from the mean) between the two sides. For the current study, the authors defined facet tropism to be bilateral angular asymmetry greater than 7°.

The angular difference inherent to facet joint tropism causes biomechanical issues. By definition, facet joint degeneration exists when one joint has more coronal orientation than the other. Farfan and Sullivan emphasized the importance of coronally facing facet joints upon the development of lumbar disc herniations. Coronally facing facet joints offer little resistance to shear intervertebral force, so that the joints tend to rotate toward the side of the more coronary facing facet joint, possibly leading to additional rotational stress on the annulus fibrosus. Loback, et al. showed that facet joint asymmetry is found more likely on the side of the coronally facing facet joint. When tropism was present, the motion segment was found to have a tendency to rotate towards the more oblique joint when axial loads were applied. This asymmetric axial rotation caused by tropism can place additional torsional loads on the intervertebral discs which can lead to intervertebral disc injury and degeneration. This biomechanical mechanism was used to describe the development of lumbar disc herniation, disc degeneration, and degenerative spondylolisthesis associated with facet tropism. Some studies have claimed that lumbar facet joint tropism does not accelerate degeneration of the facet joints. For the current study, the authors chose to investigate facet tropism and some of the findings associated with lumbar degenerative disc disease, including disc degeneration, facet joint degeneration, and spondylolisthesis (translational segmental motion).

The role of facet tropism in the pathogenesis of disc degeneration is a contested issue. Boden, et al. and Vanharanta, et al. reported no significant correlation between facet tropism and disc degeneration. However, Noren, et al. concluded that the existence of facet tropism can increase the risk of disc degeneration. Additionally, Dai reported that a significant correlation existed between facet joint tropism and the degree of disc degeneration in patients with degenerative spondylolisthesis. In the present study, no significant correlation was observed between facet joint tropism and disc degeneration at L3-L4, L4-L5, or L5-S1. However, a higher (but not statistically significant) incidence of highly degenerated discs at L4-L5 was observed within the facet tropism group.

Grogan, et al. concluded that lumbar facet joint tropism does not accelerate facet joint degeneration. They reported no significant differences in facet joint degeneration between facet joints with and without tropism. However, there are many limitations associated with this study. It was based on a small number of specimens (21 cadavers) and an even smaller number of lumbar facet joints exhibiting facet tropism (10 out of 104 lumbar facet joints). Additionally, this study did not take the level, where the tropism occurred, into consideration. Our current study included L3-L4, L4-L5, and L5-S1 facet joints belonging to 300 living participants and our findings were found to be similar to Grogan et al.’s at L3-L4 and L5-S1. However, at L4-L5, a significant correlation between facet joint tropism and facet joint degeneration was observed. Based on the fact that L4-L5 experiences the most segmental flexion and extension within the lower lumbar spine, this result suggests that the existence of facet tropism within highly mobile lumbar segments could affect the development of facet joint degeneration.

Berlemann, et al. reported that facet joint asymmetry does not seem to play a major role in the development of degenerative spondylolisthesis. However, Dai found that facet joint tropism was a predisposing factor for the development of degenerative spondylolisthesis. The present study found no association between facet tropism and translational segmental motion (such as vertebral slippage) within the lumbar spine. Our results indicate that facet tropism has no major association with the development of degenerative spondylolisthesis.

Previous reports have shown that facet orientation has a significant association with degenerative spondylolisthesis. Additionally, some of these studies reported that, in patients with degenerative spondylolisthesis, the transverse plane of facet joints was more sagittally oriented. All of these studies found that individuals with larger facetjoint angles, relative to the coronal plane (more sagittal orientation of facet joint), exhibited a higher incidence of degenerative spondylolisthesis. Although facet orientation was not taken into consideration for this study, the authors believe that it is an important element for understanding all of the factors that lead to the development of spondylolisthesis, and that this topic should be investigated further.

Another interesting factor to take into consideration is the existence of facet joint tropism within normal spines. This raises questions as to the root causality of facet joint tropism. Facet joint tropism could be caused by an inborn characteristic of the human spine, as a result of mechanical stresses on the spine (i.e., asymmetric loading of the human spine) or as a consequence of existing spinal deformities (i.e., scoliosis). Noren, et al. documented that subjects with lumbar degenerative disc disease had a higher incidence of facet joint tropism than the normal population. The nature of the relationship between facet joint tropism and degenerative changes within the lumbar spine remains a controversial topic. Essentially, there are two sides to this debate, one advocating that facet tropism leads to degeneration and the other claiming that certain degenerative statuses (i.e., degenerative spondylolisthesis) lead to facet tropism. Our results show that, at active functional spine units, facet tropism partially influences the development of facet joint degeneration. This seems to give legitimacy to the theory that facet tropism can lead to facet joint degeneration, although further investigation into the relationship between facet tropism and facet joint degeneration is necessary.