Changes in Disc Structure with Aging and Degeneration

Changes that almost universally occur in the IVD with aging include reduction in disc volume, shape, and content. Alterations in gene expression and transcription factors may be responsible for cell senescence within the disc. These senescent cells lose biochemical and synthetic capabilities, which ultimately diminishes the ability of the disc to recover from deformation and renders the matrix more vulnerable to progressive fatigue failure. The nucleus pulposus gradually becomes less hydrated, and usually by the 3rd decade of life there is already a significant decline in the number of viable cells and a loss of proteoglycans.

The early degenerative process affects the nucleus pulposus and the endplate more than the anulus fibrosus. Anabolic and catabolic processes are upregulated during the early stages of degeneration; however, anabolic repair processes fail to keep up with the catabolic processes, and matrix degeneration ensues over time. As the process progresses, the inner layers of the anulus and the nucleus pulposus gradually become indistinguishable and change into a stiff desiccated fibrocartilaginous material.

The number of arterioles supplying the peripheral disc diminishes significantly as remaining blood vessels are obliterated by calcification of the cartilaginous endplates. Loss of endplate vascularity and porosity leads to a reduction in the influx of nutrients and efflux of waste products. Lactate levels increase locally within the hypovascular disc secondary to increased production and decreased removal. Cell apoptosis occurs as a result of decreased tissue pH,¹⁸ and the biosynthetic reparative capability of the disc is impaired further.

Thinning or microfracture of the endplate alters its properties and may allow rapid outflow of fluid from the cartilage endplate on loading, rendering the hydrostatic pressure mechanisms involved in load transference less effective and uniform. Focal elevations in shear stresses at the disc level may adversely affect the disc structure further and result in annular damage. Over time, cracks develop between and through the annular lamellae. Eventually, communicating channels may develop between the peripheral layers of the anulus and the nucleus, and disc material can herniate through these fissures. The weakened anulus can develop a full-thickness defect and allow near-complete herniation of the nucleus pulposus, particularly when the disc is loaded in flexion and torsion.

The degenerative process resulting from matrix changes and internal structural disruption sets the stage for abnormal motion at the degenerated segment. Changes in disc structure alter the loading response and alignment of the spinal column. These changes can influence the facet joints, ligaments, and paraspinal muscles, which may also become pain generators. Pain does not always correlate with morphologic changes in the disc and mechanical compression, however.¹⁹ Macnab²⁰ described traction osteophytes around the vertebrae originating 2 mm from the anterior endplate, at the site of attachment of the outermost annular fibers. These osteophytes were thought to be signs of abnormal biomechanics, caused by traction at the insertion of the annular fibers into the vertebral bodies. Subsequent studies found these osteophytes to be inconsistently present.

Multiple factors lead to disc degeneration, including insufficient nutritional supply, reduction in the amount of viable cells, degradative enzymatic activity, and cell senescence and apoptosis. Alteration in loading patterns between the endplate and disc leads to annular damage and the potential for herniation. Perturbation of the disc also leads to degeneration and pain in other segmental structures such as the facet joints, ligaments, and paraspinal muscles. The initiating event leading to the onset of degeneration is unknown.

Associated Factors

Various risk factors have been implicated in the pathogenesis of lumbar disc degeneration. In a review of factors associated with IVD degeneration in elderly adults, Hangai and colleagues²¹ cited increased age, high body mass index, occupational lifting, sporting activities, and factors associated with atherosclerosis as risk factors. Multiple studies show the genetic contribution to degenerative low back pain.²² Battie and colleagues²³ estimated the familial contribution to IVD degeneration to be 34% to 61%. Cigarette smoking has also been implicated and seems to have an adverse vasoconstrictive and atherosclerotic effect on the nutrition of the IVD.^24,25 Type of occupation has also been shown to have an adverse effect on lumbar spinal segment degeneration, increasing the risk of symptomatic DDD. Studies have implicated occupations that require repetitive lifting or pulling, prolonged sitting²⁶ such as motor vehicle driving,²⁷ and whole-body vibration.²⁸

Arun and colleagues²⁹ used serial postcontrast MRI to study the effect of prolonged mechanical load on diffusion into the IVD. The authors reported that 4.5 hours at a load corresponding to 50% body weight significantly retarded the diffusion of small solutes into the center of the IVD, and it required 3 hours in an unloaded recovery phase to return the diffusion rate to that seen in the unloaded disc. Prolonged mechanical load can cause a disruption of diffusion, which may accelerate disc degeneration; however, this hypothesis has not been confirmed clinically.

The genetic predisposition to lumbar DDD and lifetime exposures were studied in a classic monozygotic twin study by Battie and colleagues.²³ These investigators reviewed 115 male identical twin pairs for exposures to common risk factors such as occupation, recreational activities, driving, and smoking. Disc degeneration was determined by MRI and clinical evaluation. In the upper lumbar spine, only 7% of the variability was explained by occupation, 16% was explained by age, and 77% was explained by familial aggregation. In the lower lumbar spine, recreational physical loading explained 2% of variability, age explained 9%, and familial aggregation explained 43%. Battie and colleagues²³ concluded that primarily genetic and other unexplained factors result in DDD, whereas commonly implicated environmental factors have only modest effects. In a 5-year follow-up study of the same twin population, the same investigators reaffirmed that genetics have a dominant role in progression of DDD, whereas occupational lifting and leisure activity had only modest effects.³⁰ The important role of genetic factors has been corroborated in other twin studies,^31,32 but it seems to be less of an explanatory factor for back pain in older people.³³

Several gene loci have been discovered that are associated with increased risk for DDD. Type IX collagen was one of the first gene loci identified with some aberrant alleles imparting a threefold or fourfold increase in relative risk.^34–36 More recent publications also implicate collagen type XI, interleukin (IL)-1, aggrecan, vitamin D receptor, matrix metalloproteinase (MMP)-3, and cartilage intermediate layer protein (CILP) as candidate genes.³⁷ The discovery of these genetic risk factors has yet to result in new useful diagnostic and treatment modalities, however.

Internal Disc Disruption

Crock¹⁹ coined the term internal disc disruption in 1970 and defined it as a painful increase in biologic activity of the IVD after injury with normal radiographic, computed tomography (CT), and myelogram examinations but an abnormal discogram. IDD as a cause of discogenic back pain is controversial. The advent of MRI has dramatically improved the detection of this entity—IDD manifests as a dark disc with relatively preserved height and contour on MRI. Pain in IDD is thought to be caused by mechanical and chemical stimulation of nociceptors within the anulus or on the surface layers of the anulus and the overlying ligamentous tissue. The hallmark of IDD is the absence of disc herniation, prolapsed disc material, segmental instability, or other radiographic abnormality.^19,38 Nerve root irritation, radicular pain, and neurologic deficits are also absent.

Radiographic changes associated with DDD—significant disc space narrowing, endplate osteophyte formation, endplate sclerosis, and gas formation within the disc space—are not seen in IDD.³⁹ MRI (dark disc) and positive discography (concordant pain in the abnormal level and not at normal adjacent levels) are required to make the diagnosis of IDD. Because of the poor sensitivity and specificity of discography, many clinicians question the existence of IDD as a clinical entity.

Degenerative Disc Disease

The relationship between degenerative disc changes and low back pain is poorly understood. Two potential sources that have been implicated as contributors to pain in patients with disc degeneration are (1) sensitization of nerve endings by release of chemical mediators and (2) neurovascular ingrowth into the degenerated disc.

The precise pathophysiologic mechanism for chemically mediated induction of hyperalgesia within the disc has yet to be fully elucidated. Radial annular tears provide a route for nuclear material and noxious chemicals to leak from the disc and contact the dural sac and nerve roots; some studies have shown that autologous nucleus pulposus alone has the capacity to produce an inflammatory response. Additionally, degradative changes can occur within nerve roots exposed to nuclear material even in the absence of mechanical compression.^38,40–42 Weinstein and colleagues⁴³ investigated the reproduction of pain on discography and concluded that various neurochemical changes within the disc are expressed by sensitized annular nociceptors. These nociceptors are terminal nerve endings of sensory neurons that selectively respond to painful stimuli by the release of substance P.⁴⁴ These chemicals are leaked into the epidural space and are transported into the axons of the exiting nerve roots. Within the nerve root, they alter the excitability of type C nerve fibers and initiate the production of inflammatory agents such as prostaglandins, which results in radicular pain.^20,45,46

In addition to material from the nucleus pulposus, many other substances in the degenerated disc have been implicated in pain generation. The role of nitric acid and phospholipase A₂ in irritation of nerve roots has been well documented.^45,47–50 Phospholipase A₂ has been implicated in multiple aspects: (1) direct activation of nociceptors, (2) nerve injury from degradation of cell membrane phospholipids, and (3) nerve injury from inflammatory mediators created from the arachidonic acid cascade (i.e., prostaglandins and leukotrienes).^51–53 Burke and colleagues⁵⁴ reported on the elevation of inflammatory mediators within the disc, such as IL-6, IL-8, and prostaglandin E₂. Other studies have shown the presence of inflammatory cytokines in the facet joints,⁵⁵ suggesting facet involvement as a pain generator via a biochemical mechanism as well. Ohtori and colleagues⁵⁶ reported on ingrowth of nerve tissue immunoreactive for tumor necrosis factor and prostaglandin P in 18 surgically harvested vertebral endplates of patients with Modic stage I and II changes who had undergone surgery. Their findings suggest that axon ingrowth into the vertebral endplate in association with Modic changes was induced by tumor necrosis factor and may be related to pain generation.

Neurovascular proliferation within and around degenerated disc elements has been proposed as another mechanism of pain generation. Normal IVDs have sparse innervation and vascularity that is distributed mainly within the outer lamellae (3 mm) of the anulus fibrosus,^57,58 whereas degenerated discs have significant neurovascular ingrowth within the inner anulus and nucleus pulposus.⁵⁹ Immunoreactive staining and acetylcholinesterase studies have shown penetration of nerve fibers within the inner third of the anulus in association with neovascularized granulation tissue.^47,57 Peng and colleagues⁶⁰ reported a histologic study of 19 IVDs harvested from surgery compared with normal control discs. The distinctive histologic characteristic of painful discs was a zone of richly innervated vascular granulation tissue extending from the outer anulus to the nucleus along the edges of fissures. Proliferation of vascular channels and sensory nerve endings rich in calcitonin gene-related peptide has also been observed in the endplate region and vertebral body adjacent to the degenerated disc. These findings suggest a role for the vertebral endplate and body as additional pain generators in DDD.⁶¹

Other studies suggest that the sensory nerve supply within the IVD is similar to visceral innervation patterns,⁶² with calcitonin gene-related peptide immunoreactive fibers that pass through the sympathetic trunks.⁶³ This visceral pattern of innervation is potentially susceptible to central sensitization, which may complicate chronic low back pain further with psychosomatic overtones.⁶⁴ Psychosocial and chronic non–back pain syndromes have been implicated in more recent publications as having a significant effect in patients with low back pain.^65–69

Internal Disc Disruption

The diagnosis of IDD is not readily apparent on a routine clinical workup. The patient is typically a younger individual 20 to 50 years old, with recurrent or persistent back pain. There may be a history of antecedent trauma or a forceful provocative event such as heavy lifting or unexpected flexion or compression force on the lumbar spine, but more often the pain is gradual in onset with no associated event or date.

The pain is characterized as a deep, dull ache in the lower lumbar region, exacerbated by rotation, flexion, and side-bending movements, and partially relieved by rest. Sitting intolerance may be a primary complaint, and pain is often relieved in a lateral recumbent position. Occasionally, there is a complaint of pain in the buttock or posterior thigh, but there is a conspicuous lack of radiculopathic symptoms. In the rare instances of associated leg pain, it is usually a late finding and pain does not follow any dermatomal pattern. In a study involving intradiscal electrothermal annuloplasty in 25 patients, O’Neill and colleagues⁷⁰ showed that stimulation of the IVD may result in low back and referred leg pain in patients presenting with symptoms of IDD. The distal distribution of pain was found to depend on the intensity of stimulation, and occasionally pain extending below the knee was produced.

Physical examination reveals decreased range of motion of the back and tenderness of the paraspinal musculature but is otherwise normal. The straight-leg raise test may reproduce back pain but not leg pain. Low back pain may also be reproduced at 20 to 30 degrees of flexion when rising from a flexed position. The sensorimotor examination is unremarkable, and deep tendon reflexes are normal and symmetrical.

Degenerative Disc Disease

Patients with DDD typically present with a history of persistent low back pain over the lumbosacral spine and sacroiliac joints and radiating into the buttocks and posterior thighs. Symptoms are often exacerbated with sitting and prolonged walking, but signs of neurologic claudication in the legs are not seen unless associated with concomitant lumbar stenosis. Radicular symptoms are rarely seen in the early stages of the disease. In end-stage disc degeneration, significant disc collapse may result in foraminal stenosis and late-onset radicular symptoms.

The physical examination is typically unremarkable except for point tenderness over the lumbar spine in the midline and over the sacroiliac joints. Range of motion of the lumbar spine may be reduced, most specifically in flexion. Extreme flexion and returning to upright from a flexed position usually cause significant discomfort. Extension is usually the least painful maneuver and may relieve pain. The straight-leg raise test may elicit some posterior thigh pain, which is often described as a stretching or pulling sensation, but there is no true radicular pain distal to the knee, unless there is coexisting foraminal stenosis. The sensorimotor examination is usually unremarkable, and deep tendon reflexes are normal and symmetrical.

Plain Radiography

Plain radiographs are the recommended initial imaging modality for patients with a complaint of low back pain. Classic comparative and cost benefit studies have been done to determine when and what radiographs to obtain.^71,72 In 1982, Liang and Komaroff⁷³ published a comparison study between performing radiographs on all patients versus performing radiographs only on patients whose pain did not improve within 8 weeks of presentation. They found that risks and costs did not justify obtaining radiographs on initial presentation. Scavone and colleagues⁷⁴ reviewed the radiographs of 782 patients and found that spot lateral and oblique films added diagnostic information in only 2% of patients. They recommended that a spine series in patients with low back pain should consist only of anteroposterior and lateral films. Generally, flexion-extension and oblique views are necessary only in patients suspected to have instability or a pars fracture. The presence of “red flags” increases the chances of diagnostic radiographic findings and may prompt the physician to obtain early radiographic studies. These “red flag” indications are summarized in Table 45–1.⁷⁵

TABLE 45–1 Practice Guidelines—“Red Flags”

Typical radiographic findings for patients with DDD include narrowing of the disc space (loss of height), endplate sclerosis, and the presence of osteophytes. Degenerative spondylolisthesis and scoliosis may occur secondarily. Advanced stages of disc degeneration may show vacuum phenomenon within the discs, a finding that represents nitrogen collection within voids in the disc.

Radiographs in patients with IDD typically show well-preserved height in the IVD and appear normal except for occasional benign spinal alignment changes. Nonstructural scoliosis and loss of lumbar lordosis may be observed in patients with sciatic list and paraspinal spasm.

Computed Tomography

CT is an excellent study to delineate osseous pathology, but it is generally not the imaging modality of choice for IDD and DDD because they are primarily soft tissue disorders. Addition of contrast material into the vertebral canal—CT myelography—significantly improves the accuracy of CT for showing pathology within the canal such as masses or stenosis, which is not a primary feature of DDD but can occur secondarily. CT myelography is the diagnostic imaging study of choice in patients with significant scoliosis and patients who are unable to undergo MRI because of implanted metal, aneurysm clips, pacemaker, obesity, or claustrophobia.

Magnetic Resonance Imaging

MRI is the best imaging modality to visualize and evaluate the neuronal and discal elements and is the most valuable adjunctive diagnostic tool in assessing disc pathology. IVDs are a highly unlikely cause of pain if MRI is completely normal and all discs are well hydrated. General MRI findings indicative of DDD include loss of water, loss of disc height, disc bulges, and signal or morphologic irregularity within the nucleus pulposus. In addition to these, MRI scans are typically examined for three specific types of findings: (1) a high-intensity zone (HIZ) in the posterior anulus, (2) dark disc with or without loss of height, and (3) endplate signal changes.

The MRI finding of a HIZ was originally described by Aprill and Bogduk⁷⁶ in 1992 and is believed to be specific for an annular tear (Fig. 45–1). Postmortem studies have shown three types of tears that can occur in the anulus: concentric, transverse, or radial.^77,78 A concentric tear is a crescentic or oval cavity created by a disruption in the short transverse fibers interconnecting the annular lamellae and is usually not visible on MRI. Concentric tears are occasionally referred to as delamination. A transverse tear represents a rupture of Sharpey fibers near their attachments to the ring apophysis at the disc periphery; these tears are typically thought to be clinically insignificant. A radial tear extending from the nucleus pulposus to the outermost surface of the posterior anulus is manifest on MRI as a HIZ.⁷⁹ HIZ is visualized on spin-echo T2-weighted images as a high-intensity signal located within the anulus fibrosus and is clearly distinguishable from the nucleus pulposus.

FIGURE 45–1 A and B, Sagittal (A) and axial (B) MRI showing high-intensity zone at L5-S1 level.

Decreased signal within the IVD on T2-weighted images with relative preservation of disc height is a relatively common finding in asymptomatic individuals. Such a disc appearance is frequently referred to as dark disc disease; however, whether these discs constitute a potential pain generator is unclear. In the absence of any psychometric abnormalities, an isolated dark disc in a patient with no other identifiable causes of back pain is considered by many clinicians to be a source of back pain.

Endplate changes (Fig. 45–2) that occur with disc degeneration have been well described by Modic and colleagues.⁸⁰ Stage I change represents edema and is characterized by decreased signal on T1 and bright signal on T2 within the endplate. In stage II, fatty degeneration in the bone adjacent to the endplates is represented by bright signal on T1 and intermediate signal on T2 sequences. Stage III changes correspond with advanced degenerative changes and endplate sclerosis and are characterized on MRI by decreased signal intensity on T1-weighted and T2-weighted images.

FIGURE 45–2 A and B, T1-weighted (A) and T2-weighted (B) sagittal MRI showing Modic stage I endplate changes.

When interpreting MRI findings, the clinician must be careful to consider the high prevalence of clinically false-positive findings. Abnormal disc findings on MRI are often found in clinically asymptomatic individuals. Boden and colleagues⁸¹ showed that approximately 30% of asymptomatic individuals have a major finding on lumbar MRI scans. In patients older than 60 years, such abnormal findings are almost universally present regardless of symptoms. Jensen and colleagues⁸² reported on 98 asymptomatic patients 20 to 80 years old and found that 52% overall had disc bulge in at least one level on MRI. Stadnik and colleagues⁸³ showed an unusually high rate of disc bulge (81%) and annular tears (56%) on MRI in 30 asymptomatic volunteers.

Abnormal MRI findings in asymptomatic patients are not indicators of future problems. Borenstein and colleagues⁸⁴ reported on 50 of the 67 patients from the study by Boden and colleagues⁸¹ at a 7-year follow-up interval and found that incidental MRI findings were not predictive of the development or duration of low back pain. Jarvik and colleagues⁸⁵ studied 148 veterans with no symptoms of low back pain for at least 4 months. They found an incidence of moderate to severe desiccation in at least one disc in 83% of patients, disc bulge in 64%, and loss of disc height in 58%. In a 3-year follow-up of the same cohort, the investigators found no association between the development of new back pain and incidental MRI findings such as Modic changes, disc degeneration, annular tears, or facet degeneration. The greatest risk factor for developing low back pain in the 3-year interval was depression.⁶⁵

Jarvik and colleagues⁸⁶ also published a report on the use of early MRI in the primary care setting. They randomly assigned 380 patients with low back pain to receive initial spine imaging via rapid MRI or plain radiography. Jarvik and colleagues⁸⁶ reported that substituting rapid MRI for x-ray studies in the primary care setting offered little additional benefit to patients in terms of secondary outcomes measures at 1 year and had the potential to increase the cost of care by $320 per patient (in 2002 dollar value). Carragee and colleagues⁸⁷ performed a prospective study of 200 asymptomatic patients to determine the rate at which new episodes of low back pain are associated with changes on MRI. On follow-up MRI in 51 patients who developed an episode of low back pain, 84% had no new finding. The most common new findings were disc signal loss (dark disc), progressive facet arthrosis, and increased endplate changes. New findings were not more common in patients developing back pain after minor trauma. The conclusion was that new findings on MRI within 12 weeks of onset of a serious episode of low back pain were unlikely to represent any significant structural change and preexisted the onset.

In consideration of the high prevalence of false-positive MRI findings, the clinician should remember that MRI does not stand alone in the evaluation of spinal pathology. When combined with a patient’s history, physical findings, and plain radiographs, selective use of MRI can provide valuable information on the source of lumbar complaints.

Discography

There is significant controversy in the literature surrounding the usefulness of discography for the evaluation of the integrity of the lumbar disc. Some investigators consider discography to be the most important tool in the diagnosis of IDD,^43,126 but more recent outcome studies¹²⁷ and a practice guideline by the American Pain Society¹²⁸ have recommended against the use of provocative discography in the diagnosis of discogenic back pain.

Discography is the only physiologic modality used to determine if a specific disc is a pain generator. Although several attempts have been made to explain the pathogenesis of pain provocation during discography, the precise pathomechanism is not well understood. There are four components to the evaluation of a discogram: (1) the pressure and volume of fluid injected into the disc, (2) the morphology of the disc being injected, (3) the subjective pain response at the level of interest, and (4) the pain response when adjacent control levels are injected.^129,130 The subjective pain response to low-pressure provocation is the most important determinant of disc derangement; reproduction of the patient’s symptoms on injection of the diseased level is essential to a positive test. A normal disc can accept 1 to 1.5 mL of contrast medium. If 2 mL or more of contrast agent is easily introduced, some degree of disc degeneration is assumed.

The use of postdiscography CT has also been reported to increase the sensitivity for the diagnosis of radial tears of the anulus.¹³¹ Because of low specificity and sensitivity, postdiscography CT is not as helpful, however, in the diagnosis of IDD. Most authors believe that to be diagnostic, not only should the pain be concordant on low-pressure injection, but also a normal control disc should be pain-free (Fig. 45–3).

FIGURE 45–3 A-C, CT discogram showing sagittal (A) and axial (B) images of normal disc morphology at L4-5 level and at adjacent level, L5-S1, disc fissure (C).

Despite being used since 1948, discography remains controversial. Holt¹²⁶ and Massie¹³² published in the 1960s on the high false-positive rate of lumbar discography, which was found to be 26% by Holt. Walsh and colleagues¹³³ later published a rigorous study on the reliability of lumbar discography. Their study compared 10 normal volunteers with 7 symptomatic patients. Although 17% of the normal discs were found to be morphologically abnormal, there were no positive pain responses. Walsh and colleagues¹³³ concluded that with modern techniques the false-positive rate of lumbar discography is not as high as reported by Holt.¹²⁶

Derby and colleagues¹³⁴ found similar results in a more recent study of 90 patients with low back pain and 16 controls. Morphologically, the prevalence of grade III annular tears was 58% among the asymptomatic control population. Presumably, asymptomatic discs in symptomatic individuals on pressure-controlled discography showed pain levels and responses similar to the control group, whereas patients with true-positive discography showed pain characteristics concordant with their usual symptoms. Derby and colleagues¹³⁴ concluded that pressure-controlled discography can differentiate between asymptomatic discs and morphologically abnormal discs.

Carragee and colleagues⁶⁸ studied the false-positive rate of low-pressure discography in a comparison of 69 volunteers with no significant low back pain and 52 patients undergoing discography in consideration for treatment of discogenic pain. Low-pressure discography was positive in at least one level in 27% of the patients with low back pain and in 25% of the controls. The false-positive rate of discography was 25% and correlated with psychosocial factors and history of chronic pain of a non-lumbar origin. In another publication from Carragee’s group,⁶⁹ psychosocial factors and chronic nonlumbar pain, such as cervical pain and somatization disorder, also correlated with positive discography in patients without symptoms of low back pain. These authors concluded that false-positive rates can be low with strict application of the Walsh protocol¹³³ in patients who do not have positive psychometric issues or other chronic pain syndromes.

In contrast to reports of high false-positive rates, two more recent meta-analyses of low-pressure discography report strong evidence to support the role of discography in identifying patients with discogenic pain.^135,136 Combined data from all studies showed an overall false-positive rate of 9.3% per patient and 6% per disc. False-positive rates among asymptomatic patients were 3% per patient and 2.1% per disc. Chronic pain was not found to be a confounder, and strength of evidence was reported as level II-2 in support of the diagnostic accuracy of discography.

Finding a “gold standard” with which discography results can be compared remains a problem. Few studies have compared the use of discography and outcomes after surgical fusion, which is perhaps the best measure for the validity of discography. Colhoun and colleagues,¹³⁷ in a study of 137 patients, reported 89% favorable outcomes in patients with positive concordant pain on discography versus 52% favorable outcomes among patients who had no painful response. Madan and colleagues¹³⁸ had different findings; 81% of 41 patients who underwent fusion based on MRI findings had satisfactory outcomes versus 76% of 32 patients who had surgery based on discography. Perhaps the most rigorous study to date was published by Carragee and colleagues.¹³⁹ In their study, success of surgical fusion was compared in 32 patients with single-level positive discogram and a matched cohort of 34 patients with single-level spondylolisthesis; 72% of the patients with spondylolisthesis met the highly effective success criteria for surgery versus only 27% of the patients with discogenic pain. Minimal acceptable success criteria were 91% and 43%. Carragee and colleagues¹³⁹ calculated a best case positive predictive value for discography of 50% to 60% and concluded that provocative discography was not highly predictive of single-level discogenic back pain.

In an attempt to improve on the poor reliability of discography, interest has turned to functional anesthetic discograms, also called discoblocks. A discoblock is a modification of discography, in which a local anesthetic, usually bupivacaine, is infused with the contrast agent into the disc to enhance the diagnostic capability of the procedure. Relief of pain after discoblock is considered diagnostic for discogenic pain. Ohtori and colleagues¹⁴⁰ published a randomized controlled study comparing standard provocative discogram with discoblock in diagnosing discogenic low back pain. Anterior lumbar interbody fusion (ALIF) procedures were performed in 15 patients whose discogenic pain was diagnosed with the aid of discography and 15 patients whose pain was diagnosed with the aid of discoblock. Outcome measures (ODI, VAS, and Japanese Orthopaedic Association score) at 3-year follow-up showed better results that were statistically significant in the group in which diagnosis was aided by discoblock.

Regardless of the details of how discography is performed, some authors have posed the question of potential ill effects resulting from perforating the lumbar disc. Carragee and colleagues¹²⁷ more recently published a report on the effect of lumbar discography in precipitating accelerated degeneration in a matched cohort study. The 10-year follow-up showed that discs that had been punctured had a greater progression of disc degeneration—35% versus 14% in the control group. There were 55 new disc herniations in the discography group versus 22 in the control group. Carragee and colleagues¹²⁷ concluded that despite using modern discography techniques with small-gauge needles, there is still an increased risk of disc degeneration, disc herniation, changes in disc and endplate signal, and loss of disc height when discography is performed.

Although discography has the potential to assist in diagnosing disc derangement, its reliance on the patient’s subjective pain response can also be problematic where secondary gain may be an issue. Psychosocial factors and chronic nonlumbar pain have also been shown to alter the diagnostic capabilities of the procedure. Finally, consideration of the consistent reports of the high false-positive rates and new findings of accelerated degeneration in discs that undergo discography make it difficult to recommend the procedure for the diagnosis of discogenic back pain. The validity of lumbar discography is very much in doubt, which is underscored by a more recent practice recommendation published by the American Pain Society. The society’s current recommendation is that provocative lumbar discography should not be used for making the diagnosis of a discogenic source of pain in the setting of nonradicular low back pain.¹²⁸ The value of using discography to assess the levels to be operated on in patients with multilevel disc degeneration has not been adequately established scientifically.

Bed Rest and Advice to Stay Active

The use of bed rest and its duration has long been debated in the literature. Treatment schedules ranging from 2 days to 6 weeks have been described.^142–144 The currently accepted recommendation⁷⁵ is limited bed rest for a maximum of 2 days because longer durations of bed rest may be detrimental to the patient’s general health while offering no benefit to the back pain. Allen and colleagues¹⁴⁵ published a review of studies documenting bed rest as treatment for 15 different conditions and found that for patients with acute low back pain there was significant worsening of outcome measures. The updated Cochrane Review of bed rest for treatment of acute low back pain reported that there is high-quality evidence that advice to rest in bed is less effective than advice to stay active.¹⁴⁶ Progressive return to activity and the initiation of a formal physical therapy or home exercise program are recommended after any initial short period of rest.

Verbunt and colleagues¹⁴⁷ explored reasons why patients sometimes use prolonged bed rest in the setting of acute episodes of low back pain. Among the study population of 282 patients, 33% reported using bed rest, and 8% remained in bed for longer than 4 days. Behavioral factors, catastrophizing, and fear of injury were associated with use of prolonged bed rest. History of back pain and pain intensity were not associated with patient use of prolonged bed rest. Additionally, patients who used prolonged bed rest in the early phase of acute low back pain were more disabled after 1 year.

Patient education and advice to stay active is now the favored recommendation. A more recent Cochrane review¹⁴⁸ of patient education and advice to stay active showed strong evidence that individual instructional sessions of 2.5 hours are more effective in returning patients to work than no intervention; however, in the setting of chronic back pain, patient education was less effective than more intensive interventions. Education sessions of shorter duration and written information were no more effective than no intervention. Another meta-analysis¹⁴⁹ of 39 randomized controlled studies evaluated advice to stay active alone or as an adjunct to other interventions such as back school or specific exercise routines. Advice as an adjunct to a specific exercise program was the most common form of treatment implemented and the best supported of the treatments studied for chronic low back pain. Outcomes among patients with acute low back pain were generally poor, but advice to stay active alone was found to be the best recommendation.

Brox and colleagues¹⁵⁰ published a systematic review of brief education in the clinical setting involving examination, information, reassurance, and advice to stay active. The authors found strong evidence that brief education was more effective for return to work but was no more effective than usual care for reduction of pain. There was limited evidence that dissemination of a back book or an Internet session was less effective than exercise. The authors concluded that a back book should not be distributed to patients as an alternative to another form of treatment.

Brace Wear and Other Orthotics

Another common conservative management technique involves the use of limited brace wear either with a recommendation to stay active or in conjunction with another form of nonoperative therapy. Calmels and colleagues,¹⁵¹ based on the results of a randomized clinical trial, recommended the limited use of a lumbar belt to improve functional status, pain, and medication use. Oleske and colleagues¹⁵² performed a randomized clinical trial of back supports and patient education in work-related back pain. These authors found no effect on patient self-report of recovery or lost work time between brace use and controls, but back supports were found to have some value in preventing recurrence of work-related back pain. A more recent Cochrane systematic review¹⁵³ of brace treatment for low back pain failed, however, to find sufficient evidence to support the use of lumbar supports to treat low back pain. Moderate evidence was found that braces are no more effective than no treatment or physical training in preventing episodes of back pain.

Use of shoe insoles has been recommended in the past for treatment and prevention of nonspecific low back pain. A more recent Cochrane systematic review¹⁵⁴ of six randomized controlled trials reported strong evidence that use of insoles does not prevent episodes of low back pain. There was limited evidence that insoles alleviated low back pain, but no conclusions or recommendations were made for use in the treatment of patients with low back pain.

Physical Therapy

Numerous physical therapy modalities and routines are described in the literature, including land-based and aquatic programs, specific protocols and exercise routines, and group treatment programs—so-called back schools. Adjunctive modalities include pain-relieving treatments such as ultrasound, iontophoresis, transcutaneous electrical nerve stimulation (TENS) unit, and heat therapy. Exercise programs commonly employ aerobic exercise, stretching, flexion and extension routines, core conditioning, and back stabilization protocols. The goal of all of these therapy regimens is to improve core strength, flexibility of the trunk and hip muscles, and conditioning. Patients often respond differently to physical therapy, so treatment programs commonly must be tailored on an individual basis. Periods of activity modification may be necessary. Patients should also be educated on proper body biomechanics; lifestyle change; and healthy living habits, such as weight control, proper nutrition, stress relaxation, and cessation of smoking.

There are multiple randomized controlled trials in the literature in support of many therapy routines or programs. Although a comprehensive review of all the various programs is not undertaken here, there have been some important updates in recent years worthy of discussion. More recent prospective randomized trials comparing physical therapy with fusion have emphasized the importance of a multidisciplinary approach with cognitive therapy, fear avoidance counseling, and intensive exercise programs.^155–157 A systematic review¹⁵⁰ found moderate evidence that fear avoidance training emphasizing exposure is more effective than graded activity increase for improvement of pain, disability, and fear avoidance.

Intensive interdisciplinary rehabilitation with emphasis on cognitive and behavioral intervention was one of the treatment recommendations made by the American Pain Society.¹²⁸ Interdisciplinary rehabilitation was defined by the society as an integrated intervention with rehabilitation plus a psychological or social or occupational component. The American Pain Society recommended that interdisciplinary therapy should be offered as a viable alternative before proceeding to surgical treatment. Noninterdisciplinary or “traditional” physical therapy is also efficacious in this patient population, but no one specific program, method, or technique is significantly better than another.

Back schools are another commonly discussed therapy modality, and there is some indication that low-intensity back schools may have some efficacy. Heymans and colleagues,¹⁵⁸ in a randomized controlled trial, found that patients who attended low-intensity back school experienced fewer sick leave days (68 days versus 75 days and 85 days) than usual care patients and patients who attended high-intensity back school. Functional status and kinesiophobia were improved at 3 months, but there was no difference in pain intensity and perception of recovery between the groups. In another randomized controlled trial, Kaapa and colleagues¹⁵⁹ found no significant benefit of back school, however, compared with physical therapy combined with cognitive therapy at 6-month, 1-year, and 2-year follow-up.

A systematic review from the Cochrane Database in 2004¹⁶⁰ concluded that there was moderate evidence suggesting that back schools in an occupational setting reduce pain and improve function and return-to-work status compared with other forms of therapy, such as exercises, manipulation, myofascial therapy, advice, placebo, and waiting list controls. Brox and colleagues¹⁵⁰ published a separate systematic review of back schools and found moderate evidence that back schools were no better than waiting lists, no intervention, placebo, or general exercises for reduction of pain.

A European economic evaluation of a randomized controlled study¹⁶¹ of intensive group therapy found no significant cost difference between intensive group therapy and standard physiotherapy. There was also no difference in clinical effect between the groups at 1-year follow-up.¹⁶² To the authors’ knowledge, there are no economic studies to date of group therapy back schools in the United States. Although low-intensity back school and programs in a work setting may have benefit versus other forms of nonoperative treatment, most of the current literature shows that back schools offer little benefit over standard physical therapy and cognitive therapy.

Adjunctive Modalities

Another treatment option for low back pain includes adjunctive physical therapy modalities such as TENS, electrical muscle stimulation, ultrasound, and iontophoresis. Poitras and Brosseau¹⁶³ reviewed randomized controlled data on the use of TENS and found that it may be useful for immediate short-term pain reduction but has little impact on patient perception of disability or on long-term pain control. A 2008 Cochrane systematic review of TENS versus placebo¹⁶⁴ concluded that there is currently not enough evidence to support the routine use of TENS for management of chronic low back pain. Even less literature is available on the use of iontophoresis and ultrasound in the setting of discogenic back pain. The few randomized controlled trials that exist focus on ultrasound in conjunction with other physical therapy regimens. The efficacy of these modalities in isolation has not been determined.

Chiropractic and Complementary and Alternative Medicine Therapies

Several studies have reported the potential beneficial effects of chiropractic treatment for acute nonspecific low back pain.^165–167 The role of chiropractic manipulations for the treatment of IDD or DDD of the lumbar spine has not been studied. Chiropractic manipulation is generally not considered effective in the treatment of chronic back pain resulting from disorders of the IVDs.¹⁶⁸ A Cochrane systematic review¹⁶⁹ failed to find evidence that spinal manipulative therapy was superior to general practitioner care, analgesics, physical therapy, exercises, or back school in the treatment of acute and chronic low back pain.

Eisenberg and colleagues¹⁷⁰ published a randomized trial of usual care therapy versus the addition of the patient’s choice of alternative therapy—chiropractic, acupuncture, or therapeutic massage—in the treatment of acute low back pain. Outcomes based on the Roland-Morris scale and subjective assessment of symptoms showed no statistically significant improvement in patients who underwent alternative therapies compared with patients treated with the usual care of limited bed rest, nonsteroidal anti-inflammatory drugs (NSAIDs), education, and activity modification. The study did show, however, an increase in patient satisfaction with care, which came at an average $244 net increase in cost per patient.

Hurwitz and colleagues¹⁷¹ had similar findings in a randomized prospective study of 681 patients with chronic low back pain comparing chiropractic care with medical treatment with 18 months of follow-up. Although less than 20% of the patients overall experienced pain relief and differences in outcome measures were not clinically significant, patients in the chiropractic group were more likely to perceive that their symptoms had improved.

Other alternative medical therapies include acupuncture, prolotherapy, and massage. The Cochrane systematic review of acupuncture¹⁷² showed superiority to placebo sham therapy and a short-term benefit that did not extend beyond first follow-up when acupuncture was used in conjunction with other conventional therapies. A more recent systematic review by Ammendolia and colleagues¹⁷³ questioned inconclusive evidence of the success of acupuncture versus sham acupuncture and called for further randomized trials to rule out the possibility of a placebo effect.

Prolotherapy is a technique that attempts to regenerate ligamentous and tendinous structures of the spine via injections of various irritant solutions. The treatment is usually performed in conjunction with spinal manipulation. There is no consensus on method, type of solution injected, or frequency of sessions. Most practitioners use various combinations of saline, dextrose, glycerin, phenol, and lidocaine. Many randomized trials and systematic reviews report conflicting efficacy of prolotherapy.^174–176 No evidence has been reported for the efficacy of prolotherapy without cointerventions such as spinal manipulation or exercise.

The efficacy of complementary and alternative modalities for the treatment of low back pain remains doubtful. The benefit of spinal manipulative therapy is also controversial, but it may improve patient satisfaction with care and perception of symptoms.

Pharmacotherapy

Judicious use of narcotic pain medications, oral steroids, and NSAIDs in patients with severe, acute back pain can provide good pain relief. Most patients with painful degenerative discs can be treated adequately on an outpatient basis. NSAIDs and acetaminophen (Tylenol) are common over-the-counter medications used to treat back pain. A Cochrane review¹⁷⁷ included 65 studies on NSAID use in low back pain. NSAIDs were found to be superior to placebo but had significantly more side effects. There is no documented difference between type of NSAID, including cyclooxygenase-2 inhibitors. Acetaminophen has an effect similar to NSAIDs but reduced risk of associated side effects when taken as directed and in general should be tried before NSAIDs. The Cochrane group concluded that NSAIDs are effective for short-term treatment of acute and chronic low back pain, but the size of the effect is small.

Opioid formulations are commonly used to treat back pain, but considering their widespread use there is a surprising paucity of high-quality randomized controlled data available on their efficacy. A Cochrane database meta-analysis¹⁷⁸ of opioid use found only four studies, three of which focused on the use of tramadol. Pooled data found that tramadol, an atypical opioid, was more effective than placebo for pain relief and showed a slight improvement in functional scores. The only randomized controlled study of classic opioids¹⁷⁹ was a comparison with naproxen. Opioids were found to be more effective for pain relief but were not more effective for improving function than naproxen. The Cochrane review authors concluded that the benefits of opioids for the treatment of chronic low back pain are questionable, and further well-designed randomized controlled studies need to be performed. Two subsequent systematic reviews^180,181 of opioid use in the setting of chronic low back pain concluded that there is evidence to support the efficacy of opioids for short-term relief of pain only. There is little evidence for long-term opioid use, which is fraught with an incidence of aberrant consumptive behavior approaching 25%.

Use of opioid pain medication has many problems ranging from minor side effects such as constipation and nausea to severe complications including respiratory depression, altered mental status, and insidious issues with tolerance and addiction. Another more recent concern with opioid use is related to the combination of opioids and acetaminophen in commonly prescribed formulations.¹⁸² The maximum recommended daily dose of acetaminophen for adults and children older than 12 years is 4 g; thus concern arises when patients inadvertently take larger doses in the setting of prescription drug abuse. The potential to inadvertently take hepatotoxic or lethal doses can be a concern in the setting of prescription drug abuse. An advisory committee from the U.S. Food and Drug Administration (FDA)¹⁸⁴ recommended the addition of a boxed warning on the risk of acetaminophen overdose and suggested elimination of combination opioid-acetaminophen formulations. Care should be exercised when prescribing opioid pain medications. They are best given for only a few days in the setting of severe acute back pain, and their use in patients with chronic back pain is not recommended.

Oral tapering courses of steroids have also been found useful for decreasing symptoms of low back pain, most specifically in patients with disc herniations.^80,185 Steroids can cause gastrointestinal bleeding, and gastrointestinal protective agents should be used simultaneously with oral steroids to reduce the risk of this complication.

Muscle relaxants are another class of medication routinely used in the treatment of muscle spasm associated with low back pain. Their use should be limited to very short courses because of their addictive potential. The Cochrane review¹⁸⁶ of muscle relaxants for the treatment of back pain included 30 trials evaluating the use of benzodiazepines, nonbenzodiazepines, and antispasmodic muscle relaxants. Strong evidence for the efficacy of muscle relaxants over placebo was reported for short-term pain relief in the setting of acute back pain. No difference between the various drugs and classes was discerned. More trials to determine the efficacy of muscle relaxants compared with other analgesics and NSAIDs were recommended.

The last class of medications commonly prescribed in the setting of back pain is antidepressants. Their use may be particularly beneficial in patients presenting with chronic low back pain in association with altered mental status, depression, anhedonia, sleep disturbances, agitation, and anorexia. Clinical studies^187–189 supporting the use of tricyclic antidepressants (TCAs) have shown an improvement in mood and sleep patterns. Low doses of TCAs also affect membrane potentials of peripheral nerves, which may be a mechanism by which they produce pain reduction. A 2003 review¹⁹⁰ of antidepressants in the treatment of chronic low back pain found that TCAs have a moderate effect on pain reduction in patients with no history of depression but reported conflicting evidence for improvement in functional outcomes. Physicians prescribing TCAs should be aware of potentially serious side effects involving orthostatic hypotension and cardiovascular perturbations. In a systematic review,¹⁹¹ selective serotonin reuptake inhibitors, another common class of antidepressants, failed to show efficacy in the treatment of chronic low back pain and should be reserved for emotional or psychiatric disturbances related to back pain and not used as a primary treatment for symptoms of back pain.

Keller and colleagues¹⁹² published a meta-analysis of nonsurgical management options for low back pain. These authors reported that behavioral therapy, exercise therapy, and NSAIDs had the largest effect of the modalities studied. Machado and colleagues¹⁹³ published a separate large meta-analysis of placebo-controlled randomized trials of various forms of nonoperative treatment for nonspecific low back pain. Small improvements in complaints of pain were found in patients treated with traction, physical therapy, antidepressants, and NSAIDs; moderate improvements were found in patients treated with opioid analgesics, muscle relaxants, facet injections, and nerve blocks.