LUMBAR DISC DISEASE

LUMBAR DISC DISEASE

Descriptions of treatment for low back pain (LBP) date to Hippocrates (460-370 BCE), who reported joint manipulation and use of traction.

Onset of LBP often is associated with bipedal ambulation.

Theories propose that this transformation in the mechanics of locomotion is the inciting evolutionary event that made the lumbar spine susceptible to degenerative disease.

Degeneration is universal to structures that comprise the functional spinal unit, composed of 2 adjacent vertebral bodies and the intervertebral disk. The disk and 2 zygapophyseal joints at the same level function as a trijoint complex.

As humans age, they endure both macrotraumas and microtraumas and undergo changes in body habitus that alter and redistribute biomechanical forces unevenly on the lumbar spine.

Natural progression of degeneration of the lumbar segment with motion proceeds with characteristic anatomic, biomechanical, radiologic, and clinical findings in lumbar degenerative disk disease (LDDD).

PATHOPHYSIOLOGY

Posterior elements of the lumbar spinal functional unit typically bear less weight than anterior elements in all positions. Anterior elements bear over 90% of forces transmitted through the lumbar spine in sitting; during standing, this portion decreases to approximately 80%.

As the degenerative process progresses, relative anterior-to-posterior force transmission approaches parity.

The spine functions best within a realm of static and dynamic stability. Bony architecture and associated specialized soft tissue structures, especially the intervertebral disk, provide static stability.

Dynamic stability, however, is accomplished through a system of muscular and ligamentous supports acting in concert during various functional, occupational, and vocational activities.

The overall mechanical effect of these structures maintains the histologic integrity of the trijoint complex. Net shear and compressive forces must be maintained below respective critical minima to maintain trijoint articulation integrity.

Persistent, recurrent, non mechanical, and/or excessive forces to the motion segment beyond minimal thresholds lead to microtrauma of the disk and facet joints, triggering and continuing the degenerative process.

Degenerative cascade, described by Kirkaldy-Willis, is the widely accepted pathophysiologic model describing the degenerative process as it affects the lumbar spine and individual motion segments.

This process occurs in 3 phases that comprise a continuum with gradual transition, rather than 3 clearly definable stages.

PHASE I

The dysfunctional phase, or phase I, is characterized histologically by circumferential tears or fissures in the outer annulus.

Tears can be accompanied by endplate separation or failure, interrupting blood supply to the disk and impairing nutritional supply and waste removal. Such changes may be the result of repetitive microtrauma.

Since the outer one third of the annular wall is innervated, tears or fissures in this area may be painful. Strong experimental evidence suggests that most episodes of LBP are a consequence of disk injury, rather than musculotendinous or ligamentous strain.

Circumferential tears may coalesce to form radial tears. The nucleus pulposus may lose its normal water-imbibing abilities as a result of biochemical changes in aggregating proteoglycans.

Studies suggest proteoglycan destruction may result from an imbalance between the matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1). This imbalance

results in diminished capacity for imbibing water, causing loss of nuclear hydrostatic pressure and leading to buckling of the annular lamellae.

This phenomenon leads to increased focal segmental mobility and shear stress to the annular wall.

Delamination and fissuring within the annulus can result. Annular delamination has been shown to occur as a separate and distinct event from annular fissures. 

Microfractures of collagen fibrils in the annulus have been demonstrated with electron microscopy. MRI at this stage may reveal desiccation, disk bulging without herniation, or a high-intensity zone (HIZ) in the annulus.

Structural alteration of the facet joint following disk degeneration is acknowledged widely, but this expected pathologic alteration does not necessarily follow.

Changes associated with zygapophyseal joints during the dysfunctional phase may include synovitis and hypomobility. The facet joint may serve as a pain generator.

PHASE II

The unstable phase, or phase II, may result from progressive loss of mechanical integrity of the trijoint complex.

Disk-related changes include multiple annular tears (eg, radial, circumferential), internal disk disruption (IDD) and resorption, or loss of disk-space height.

Concurrent changes in the zygapophyseal joints include cartilage degeneration, capsular laxity, and subluxation. The biomechanical result of these alterations leads to segmental instability.

Clinical syndromes of segmental instability, IDD syndrome, and herniated disk seem to fit in this phase.

PHASE III

The third and final phase, stabilization, is characterized by further disk resorption, disk-space narrowing, endplate destruction, disk fibrosis, and osteophyte formation.

Diskogenic pain from such disks may have a higher incidence than that of the pain from the disks in phases I and II; however, great variation of phases can be expected in different disks in any given individual and individuals of similar ages vary greatly.

FREQUENCY

Lifetime incidence of LBP is reported to be 60-90% with annual incidence of 5%. Each year, 14.3% of new patient visits to primary care physicians are for LBP, and nearly 13 million physician visits are related to complaints of chronic LBP, according to the National Center for Health Statistics.  

SEX

LBP secondary to degenerative disk disease affects men and women equally.

AGE

LBP secondary to degenerative disk disease is a condition that affects young to middle-aged persons with peak incidence at approximately 40 years.

With respect to radiologic evidence of LDDD, the prevalence of disk degeneration increases with age, but degenerated disks are not necessarily painful.

CLINICAL

HISTORY

The patient's history is an extremely valuable tool for identifying the intervertebral disk as the nociceptive source.

Classic historic features are associated with a diskogenic etiology of mechanical low lumbar complaints.

The clinician must ask several key questions to elicit the information necessary for correct diagnosis. These questions address events that cause the symptoms, the location and nature of the symptoms, any exacerbating and mitigating factors or positions, and the patients' medical and surgical history.

Often, a nociceptive source of back pain is not found.

• Patients with diskogenic pain typically describe an inciting traumatic event resulting in sudden forced flexion and/or rotational moment; however, some patients describe a spontaneous onset of symptoms.

• Symptoms, usually isolated in the low lumbar region and buttocks, can vary, with referral to the lower thoracic and/or upper lumbar region, abdomen, flanks, groin, genitals, thighs, knees, calves, ankles, feet, and toes.

• Classic diskogenic pain is exacerbated by activities that load the disk, such as sitting, arising from a seated position, awaking in the morning, lumbar flexion with and without rotation/twisting, lifting, vibration (eg, riding in a car), coughing, sneezing, laughing, and the Valsalva maneuver.

• Symptoms are mitigated by lying on the side with hips and knees flexed (fetal position), by changing positions frequently, and/or by engaging in activity.

• Diskogenic pain is usually described as aching; however, a wide spectrum of adjectives can be reported from soreness to stabbing pain.

• Patients with a surgical history of lumbar arthrodesis, lumbar discectomy, or lumbar laminectomy have changes in lumbar spine biomechanics resulting in susceptibility to diskogenic disease.

• The patient's medical history should be investigated with specific inquiry directed toward a personal history of cancer, arthritis, or infection or systemic disease that could increase risk of infection.

• The review of systems should include assessments for fever, incontinence, symptoms suggestive of metastasis or metabolic disease, and psychological issues including depression and drug use or abuse.

PHYSICAL

Physical examination is an important adjunct to history in determining diskogenic etiology of symptoms, beginning with the first view of the patient in the examination room.

The patient may prefer to stand, pace, or sit in a reclining position since these positions usually alleviate symptoms of diskogenic etiology.

v  Note the patient's height and weight, as obesity may produce excess load to the low lumbar intervertebral disks.

v  Inspection of the low lumbar region is important since this part of the examination may offer a clue to history of lumbar surgery if a scar exists. Inspection while the patient is standing and during forward flexion and extension may reveal a kyphotic or scoliotic deformity. Inspection and palpatory examination should be performed in flexion with the patient standing and seated to determine whether the pain source is in the pelvis or sacral area.

v  Palpation of the lumbar paraspinals and spine stabilizers may elicit tenderness, as these muscles may be tight, have active or latent trigger or tender points, or be in reactive muscle spasm.

v  A step deformity, in which the spinous process of the segment involved protrudes ventrally, may exist as a consequence of spondylolisthesis.

v  Measure the lower extremity circumference at mid thigh and mid calf at the same time of day so comparable results are obtained; they should be symmetric. Hips, knees, and ankles should have full range of motion (ROM), without crepitus or effusions.

v  Diskogenic stress maneuvers usually reproduce the patient's low lumbar and buttock symptoms. These maneuvers include pelvic rocking and sustained hip flexion.

o    Perform pelvic rocking with the patient in a supine position. Flex the patient's hips until the flexed knees approximate to the chest; then, rotate the lower extremities from one side to the other.

o    Perform sustained hip flexion with the patient supine; raise the patient's extended lower extremities to approximately 60° in relation to the examination table. Then ask the patient to hold the lower extremities in that position and release. Query the patient regarding reproduction of low lumbar and/or buttock pain. Then lower the extremities successively approximately 15°, and, at each point, note the reproduction and intensity of pain. The test is positive if the patient complains of low lumbar and/or buttock pain of increasing intensity as the extremities are lowered at successive angles. Sacroiliac joint stress maneuvers do not provoke pain. Root tension signs are negative.

v  Orientation, mood, and affect usually are within normal limits, and excessive emotional liability may be a sign of nonorganic pathology. These provocative maneuvers should not be accompanied by exorbitant demonstrations of perceived pain. Such overt pain behavior should alert the clinician to important psychosocial issues.

v  Normal neurologic examination, with intact pinprick sensation throughout all dermatomes, full muscle strength throughout all myotomes, and symmetric muscle stretch reflexes, are associated with diskogenic disease. Two muscles should be tested with reflexes elicited representing each lumbar root; this test helps determine whether the problem is root pathology or a focal neuropathy; the straight leg test also should be performed in supine and seated positions.

v  Gait usually is normal.

v  Lumbar ROM usually is limited and painful, chiefly into flexion; however, extension also can be restricted and painful. Lumbar ROM should be assessed in flexion, extension, lateral bending, and rotation. A careful, systematic, and thorough structural examination should be performed to assess for subtle abnormal findings that may be amenable to manual therapy or manipulation.

CAUSES

The cause of LDDD is unknown.

Several theories cite traumatically induced acute annular tear as the inciting pathologic event. Other theories suggest that degeneration of the lumbar disk is a natural part of aging; however, these theories do not explain spontaneously occurring annular tears and disk degeneration in the young.

Therefore, the cause of LDDD is most likely multifactorial. Various genetic, environmental, autoimmune, inflammatory, traumatic, infectious, toxin-induced, and other factors, alone or in various combinations, may result in initiation and progression of degeneration of the lumbar disks in a way that has not been elucidated.

DIAGNOSIS

LABORATORY STUDIES

• No clinically relevant laboratory studies associated with LDDD have been found.

IMAGING STUDIES

• Radiography

  • Plain radiographs can be helpful in visualizing gross anatomic intervertebral disk changes. Obtain standing anteroposterior (AP) and lateral views. Intervertebral disks are visualized best on lateral views. Plain images are often not helpful unless evidence suggests a more dangerous etiology for LBP.

  • Signs of degeneration include loss of disk height, sclerosis of the endplates, or osteophytic ridging. In addition, spondylolisthesis can be diagnosed and the degree of slippage visualized easily on lateral images. Oblique views may be helpful is spondylolysis is suggested.

  • Coned-down lateral view provides a detailed look at the L5-S1 interspace. Flexion/extension images may help determine whether excess motion occurs between 2 vertebral bodies.

• Nuclear imaging

  • Nuclear imaging assesses tissue metabolism by using radionuclide labeled technetium-99m that emits radiation in proportion to its attachment to targeted structures. These studies have not been helpful in identifying disk pathology.

  • Myelography may help in assessing neural compression, but it is not helpful in evaluating intervertebral disks unless it is combined with CT scanning.

• CT scanning

  • CT can be used to identify symmetric uniform degenerative changes of the disk that result in a diffuse annular disk bulge, seen as diffuse peripheral extension of disk material. The margin of the annular bulge is usually smooth in contour but may be asymmetric. Overlapping 3- to 5-mm axial sections in 3-mm increments with multiplanar reformations is the optimal protocol. Sagittal reformations or CT scans may demonstrate loss of disk height. An intradisk vacuum phenomenon is seen commonly as focal or linear areas of markedly diminished density within the intervertebral disk.

  • CT also may demonstrate endplate degenerative changes, including sclerosis and cortical irregularity with erosions. CT allows for visualization of disk degeneration, bulging, and herniations but not with the detail of MRI. Degeneration of the intervertebral disk and endplate commonly is observed at autopsy and in imaging studies in asymptomatic patients. In the lumbar spine, CT scans are abnormal in 35% of asymptomatic volunteers of all ages and in 50% of persons aged 40 years or older.

• Magnetic resonance imaging

  • MRI is currently the criterion standard imaging modality for detecting disk pathology. MRI has demonstrated degenerative changes in 3 times as many motion segments as contrast-enhanced CT scan. MRI uses a magnetic field to obtain direct multiplanar images with excellent soft-tissue contrast, and MRI provides superb resolution and precise localization of intervertebral disks.

  • On MRI, degeneration of the intervertebral disk results in diminished signal intensity on T1- and T2-weighted images. These signal intensity changes are due to diminished water and glycosaminoglycan content and increased collagen content of the intervertebral disk. Sagittal images provide the best depiction of the loss of intervertebral disk height. Bulging of the disk annulus can be demonstrated on axial and sagittal images. Posterior extension of the disk annulus by >1.5 mm is invariably correlated with radial tears of the disk annulus. Furthermore, tears of the annulus fibrosus can be visualized as HIZ lesions (HIZL).

  • In vitro, MRI can demonstrate radial tears of the disk annulus. The sensitivity of MRI is 67% compared with diskography in detecting radial annular tears. Focal enhancement of radial tears may be seen on gadolinium-enhanced T1-weighted MRIs. This enhancement has been attributed to granulation tissue in the tear. A vacuum phenomenon is demonstrated as an area without signal intensity in the intervertebral disk; this is best appreciated on sagittal T1-weighted images. MRI shows notable abnormalities in approximately 30% of asymptomatic people of all ages, and in 57% of those aged 60 years or older. Disk degeneration or a bulging intervertebral disk is observed in 35% of subjects aged 20-39 years and in nearly 100% of those aged 60-80 years.

  • An important component of the degenerative process of the lumbar intervertebral disk is degeneration of the cartilaginous endplate. The cartilaginous endplate cannot be discretely identified on MRI because of its thinness and the chemical-shift artifacts at the endplate; however, MRI demonstrates reactive changes in the bone marrow due to the degenerative process in the diskovertebral joint associated with chronic repetitive stress. Disruption and fissuring of the endplate with granulation tissue and reactive woven bone result in endplate changes where vascularized fibrous tissue replaces adjacent marrow.

  • Type 1 endplate changes are characterized by decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. Disruption of the endplate with replacement of the hematopoietic elements in the adjacent marrow by fat result in type 2 changes. Consequently, type 2 endplate changes are nearly isointense with fat, have hyperintensity on T1-weighted images and isointensity or slight hypointensity on T2-weighted images. Type 1 changes appear to convert to type 2 changes over time. Extensive bony sclerosis with thickening of subchondral trabeculae results in type 2 endplate changes. Type 3 changes have decreased signal intensity on both T1- and T2-weighted images.

• MRI and CT scanning have considerable false-positive rates and less frequent false-negative results.

OTHER TESTS

• Plain radiographs, myelography (of value only in patients with nerve impingement on moving or standing), enhanced or non enhanced CT, and nuclear imaging cannot depict painful disks. MRI is helpful in showing changes in signal intensity generated by the nucleus pulposus and, occasionally, in adjacent vertebral bodies; however, the same types of MRI changes can be seen in lifelong asymptomatic individuals.

• Both April and Schellhaus have suggested that HIZL observed on MRI may be a marker of a painful disk. However, findings from 4 independent studies of the clinical usefulness of HIZL as an indicator of a symptomatic disk are not supportive of this conclusion.

• Provocation of concordant pain with lumbar diskography has been well demonstrated. The key feature of diskography is the patient's response to disk stimulation and not the appearance of the disk.

• Results of physiologic testing explicitly determine whether a disk is painful. Specificity of diskography in this regard has been well established by the work of Walsh and colleagues.

• Because the only available diagnostic intervention that identifies a symptomatic disk is provocative diskography, consider ordering this diagnostic tool before surgery. Diskography remains controversial; some spinal physicians do not acknowledge its reliability or validity. Their contention primarily rests in a desire to prevent inappropriate surgery because of a potential to abuse diskography combined with the view, albeit unsubstantiated, that IDD represents a constellation of symptoms rather than a specific diagnosis. The value of diskography is debatable. Actual demonstration of disk disruption has been shown to be no more important than pain reproduction.

• After diskographic assessment, refer patients for surgery, nonoperative treatment, or psychological care. The best candidates for surgery should have involvement of only 1 disk, possibly the 2 most caudal lumbar disk segments, or the 2 most cephalic disks. Refer patients with any other combination of disk involvement for nonsurgical pain modulation.

• Electrodiagnostic testing (nerve conduction studies and electromyography) is warranted when their results may change the patient's therapy. In particular, electrodiagnostic testing is indicated (1) if patients have symptoms suggestive of cauda equina syndrome and their imaging studies are not diagnostic; (2) if imaging studies show an abnormality not consistent with the symptoms; (3) if such studies appear to be normal despite clinical suspicions; (4) if the clinician suspects focal nerve entrapment, polyneuropathy, or myopathic condition; and (5) if the clinician needs to identify which of several anatomic lesions in the spine is the cause of radicular symptoms.

• If a malignancy is suggested, laboratory studies, including determination of the complete blood count, erythrocyte sedimentation rate, and alkaline phosphatase levels and serum protein electrophoresis, may be helpful. Conversely, if a rheumatologic etiology is considered, tests for antinuclear antibody, rheumatoid factor, uric acid, and HLA-B27 levels may be beneficial.

PROCEDURES

• Initial reports of epidural injections almost a century ago described the instillation of cocaine into the epidural space to treat lumbago and sciatica. In the early 1900s, epidural injection of local anesthetic was used to treat intractable sciatica. In 1952, Robecchi and Capra reported success with the first epidural steroid instillation in treating lumbar and associated sciatic pain. Instillation of steroid into the epidural space has become a common modality in treating lumbar and lower-extremity pain due to a suspected inflammatory etiology.

• Patient characteristics that may suggest an unfavorable or suboptimal response to possible epidural steroid injection (ESI) are a long duration of symptoms, a nonradicular diagnosis, unemployment because of pain, smoking, increasing use of pain medication, increasing number of treatments for pain, pain not relieved by medication, and pain not increased by activity.

• Optimal timing for the administration of epidural steroids has not been elucidated. Patients generally undergo conservative palliative measures (eg, NSAID therapy, lumbar-spine stabilization therapy) before they are considered for ESIs. However, do not delay epidural injections when conservative treatments do not seem to be helping. Delaying aggressive treatment may allow the ongoing inflammatory process to result in fibrosis and possibly permanent damage.

• How often ESIs can be administered is unknown. Practitioners often wait as long as 2 weeks before reassessing the patient for a response to the injection and for possible reinjection. This practice became popular after Swerdlow and Sayle-Creer suggested that steroid injected into the epidural space may remain in situ for up to 2 weeks.

• In 1972, Winnie and colleagues emphasized the importance of placing medication as close to the site of pathology as possible to maximize the outcome. They reported improvement in 80% of patients in whom steroids were injected at the site of pathology. The best route for injection of steroids into the epidural space in patients with a diskogenic source is transforaminal. This route allows the clinician to drive the injected steroid ventrally with approximately 5 mL of local anesthetic to bathe the suspected diskogenic inflammatory source. The efficacy of this approach has been demonstrated in various prospective studies in lumbar axial pain syndromes and in those associated with corroborative radicular pain.

  • Only 2 nonrandomized, retrospective studies have address the outcome of transforaminal ESIs on spinally mediated lumbar axial pain due to diskogenic pathology without imaging evidence of nerve-root involvement.

    • Rosenberg and colleagues reported greater than 50% pain reduction after 1 year in 59% of patients.

    • Manchikanti and colleagues examined patients with spinally mediated lumbar axial pain treated with blind interlaminar ESI, fluoroscopically guided caudal injection, or fluoroscopically guided transforaminal injection. The authors reported superior short- and long-term pain relief with the transforaminal route. This conclusion makes anatomic sense because transforaminal ESIs likely distribute the injectate more focally to the ventral epidural space than do the interlaminar and caudal routes. Therefore, is may be most target specific when one attempts to deliver medication to the focus of a posterior diskogenic inflammatory response.

  • The optimal route for injection of corticosteroids into the epidural space at the site of pathology in patients with diskogenic mediated lumbar axial pain syndromes with corroborative radicular involvement is the transforaminal route. This approach allows the clinician to deliver the injectate, composed of a betamethasone 6-12 mg and 1% lidocaine 0.5-1 mL. The goal is to precisely eradicate the known inflammatory response emanating from the potentially inflammagenic herniated nucleus pulposus (HNP) focally on the corroborative inflamed nerve root sleeve.

  • The efficacy of the aforementioned approach has been demonstrated in 4 randomized prospective, double-blind controlled clinical trials.

    • Riew and colleagues reported the results of fluoroscopically guided lumbar transforaminal injections in 55 patients with imaging evidence of nerve-root compression and corroborative radicular symptoms. Twenty-eight patients received bupivacaine and betamethasone, and 27 received bupivacaine. At 13- to 26-month follow-up, 33.3% of patients in the bupivacaine group decided not to have surgery compared with 71.4% of the bupivacaine-and-betamethasone group. The difference in surgical rates was statistically significant (P <.004). This study demonstrated the beneficial effect of precisely delivered corticosteroids in obviating operative treatment in patients with HNP and/or spinal stenosis.

    • Kraemer and colleagues reported long-term pain relief with transforaminal ESI. In their study, 49 patients with lumbar radicular pain were randomly assigned to into a corticosteroid group and control group.

    • Karppinen and colleagues reported 160 consecutive patients with symptomatic herniated disks with no history of lumbar-spine surgery. Patients were randomly selected for a corticosteroid group or a normal-saline group. Outcome measures obtained at 2 weeks, 3 months and 6 months included pain relief, sick leave, medical costs, findings on the Nottingham Health Profile, and future requirements for surgical intervention. Transforaminal ESI provided significant short- and long-term improvement in all of the outcome measures.

    • Thomas and colleagues reported the relative effectiveness of fluoroscopically guided lumbar transforaminal ESIs versus blind interlaminar ESIs in patients with radicular pain. Transforaminal ESIs were superior a variety of outcome measures, including finger-to-floor lumbar flexion, daily activity (including work and vocational function), and Dallas pain scores. Findings from this direct comparison underscore the importance of fluoroscopic guidance and of delivering medication accurately and precisely to the site of a potential ongoing inflammatory response.

  • In a prospective nonblinded randomized study by Buttermann, transforaminal ESIs provided efficacy measured by reduced symptoms and disability and obviation of surgery at a follow-up of up to 3 years. Patients had large (>25% of the cross-sectional area of the spinal canal) symptomatic lumbar herniated disks. Buttermann also reported that patients who had short-term improvement or ineffectiveness of transforaminal ESIs and who require surgical diskectomy had no adverse affect in the outcome of that surgery due to the temporal delay caused by the trial of transforaminal ESIs.

  • Findings from several prospective nonrandomized clinical trials of the efficacy of transforaminal ESI strongly suggest the beneficial effects of transforaminal ESIs for HNP that causes lumbar axial pain with corroborative radicular pain.

    • Weiner and colleagues reported that 21 of 28 patients with a CT-documented HNP and corroborative lower-extremity pain had moderate or complete pain relief after receiving a single transforaminal infusion of betamethasone and 1% Xylocaine; patients did not require surgery at an average of 3.4 years during follow-up.

    • Lutz and colleagues reported 69 patients, with an average of 22 weeks of symptoms, who had MRI evidence of a HNP and radicular pain. Patients underwent an average of 1.8 transforaminal injections of betamethasone and 1% Xylocaine followed by a 6- 12-week course of lumbar-spine stabilization therapy. At an average of 80 weeks of follow-up, 75% of patients had a success outcome (defined as pain reduction by 50% or more and return to previous or near-previous level of function).

    • In a retrospective evaluation, Wang and colleagues demonstrated significant short- and long-term symptomatic improvement and the avoidance of diskectomy in 77% of patients with lumbar disk herniations who were treated with 1-6 transforaminal ESIs.

• The literature discussed above strongly suggests that transforaminal ESI should be the standard of care for index interventional spinal procedure in patients with spinally mediated lumbar axial pain syndromes associated with radicular involvement due to diskogenic disease and/or HNP when more conservative measures fail. Furthermore, in most cases of HNP, the known phagocytic immunologic response and consequent benign anatomic natural history contributes to the relatively high long-term success rates of transforaminal ESIs.

• Contraindications to steroid instillations in the epidural space are pregnancy (because of the adverse effects of fluoroscopy on the fetus), hypersensitivity to any component of the injected steroid, bacteremia, full anticoagulation, and bleeding diathesis. Other concerns are elevation of serum glucose levels in patients with diabetes, elevation of blood pressure in hypertensive patients, and fluid retention in patients with congestive heart failure. Use of aspirin and other NSAIDs has not been demonstrated to predispose patients to clinically significant bleeding when they are receiving epidural injections.

HISTOLOGIC FINDINGS

The lumbar intervertebral disk is composed of the nucleus pulposus and annulus fibrosis. The disk is intimately related as a functional unit to the cartilaginous endplate.

The intervertebral disk contains water, collagen, and proteoglycans. The nucleus pulposus normally is well hydrated, containing approximately 85-90% water in children aged 0-10 years and 70-80% water in adults.

Elongated fibrocytes are organized loosely, forming a gelatinous matrix. The nucleus has a higher content of proteoglycans than the disk annulus.

The annulus fibrosis contains 75% water in children aged 0-010 years and 70-80% water in adults.

The peripheral annulus is primarily composed of type I collagen, lending tensile strength to the intervertebral disk.

The inner annulus is primarily composed of type 2 collagen, which, in conjunction with the nucleus pulposus, provides compressive strength.

Type 2 collagen may contain more water than type 1 collagen.

The collagenous lamellae are fewer, thinner, and more tightly packed posteriorly than anteriorly. The central depression of the vertebral endplate is covered by hyaline cartilage.

With age-related degeneration, the volume of the nucleus pulposus diminishes with decreasing hydration and increasing fibrosis.

Changes in water content are from alteration in the relative composition of proteoglycan, as well as decrease in the extent of aggregating proteoglycans.

By age 30 years, in-growth of fibrous tissue into the nucleus results in an intranuclear cleft. Fibrocartilage, derived from cells in the annulus and endplate, gradually replaces mucoid material within the nucleus. Gradual loss of definition between nucleus and inner annular fibers occurs.

In the final stages of degeneration, the nucleus is replaced completely by fibrocartilage indistinguishable from the fibrotic disk annulus. Specifically, the type 1 collagen content of the disk annulus increases, especially posteriorly, and type 2 collagen content diminishes.  

Cartilaginous metaplasia begins in the inner annular fibers with changes in the overall fiber direction from vertical to horizontal. Infolding of fibers of the outer annulus occurs early with myxoid degeneration of the outer annular fibers.

Concentric and/or transverse tears in the annulus fibrosis are frequent findings.

Peripheral tears are more frequent posterior or posterolateral where the annular lamellae are fewer. The development of a radial tear, particularly a tear extending to the disk nucleus, is a major hallmarks of disk degeneration.

The degenerated intervertebral disk loses height and overall volume. Herniation of both nuclear material and annulus fibrosis may occur through the tear. With aging, the cartilage endplate may become thin and eventually calcified. In advanced disk degeneration, the cartilage endplate is calcified, with fissuring and microfractures.

For a structure to be considered a pain generator, it must have a nerve supply, it must be susceptible to disease or injuries known to be painful, and it must be capable of causing pain similar to that observed clinically.

The superficial layers of the annulus fibrosis contain nerve fibers in the posterior portion of the annulus, which are branches from the sinuvertebral nerves. The sinuvertebral nerves are branches of the ventral rami. They also contain fibers derived from the grey ramus.

Small branches from the grey ramus communicans or sympathetic fibers innervate the anterior longitudinal ligament and lateral and anterior annulus. The grey ramus communicans joins the sinuvertebral nerve that reenters the intervertebral foramen and spinal canal to innervate the posterior annulus and the posterior longitudinal ligament.

A dense nerve network on the posterior portion of the lumbar intervertebral disk has been demonstrated in rats. This network disappears almost completely after total resection of bilateral sympathetic trunks at L2-L6.

In rats, sympathetic nerves bilaterally and multisegmentally innervate the posterior portion of the lumbar intervertebral disk and posterior longitudinal ligament. A variety of free and complex nerve endings have been demonstrated in the outer one third to one half of the annulus. Coppes and colleagues observed that disk innervation was more extensive in severely degenerated lumbar disks than in compared normal disks.

Substance P immunoreactivity suggests nociceptive properties of at least some of these nerves, which provides further evidence for a morphologic substrate of diskogenic pain. Nerve fibers were restricted to the outer or middle third of the annulus in control samples.

In the patient population undergoing spinal fusion for chronic LBP, nerves extended into the inner third of the annulus fibrosis in 46% and into nucleus pulposus in 22%.

The findings that isolated nerve fibers express substance P deep within diseased intervertebral disks and the association with pain suggests an important role for nerve ingrowth into the intervertebral disk in the pathogenesis of chronic LBP.

Weinstein and colleagues identified substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptides (VIP) in the outer annular fibers of the disk in rats.These chemicals are all related to pain perception.

Substance P–, dopamine-, and choline acetyltransferase–immunoreactive nerve fibers are found in human longitudinal ligaments that have been removed surgically. These findings not only provide evidence to support the first criterion but also reveal changes associated with painful disks.

TREATMENT

PHYSICAL THERAPY

Physical rehabilitation with active patient participation is a key approach to treatment of patients with diskogenic pain.

Physical therapy programs prescribed specifically to address the primary site of injury and secondary sites of dysfunction can provide a means of treatment, with or without adjunct medications, therapeutic procedures, or surgical intervention.

Relative rest, which restricts all occupational and avocational activities, for up to the first 2 days after an acute episode, may be indicated to help calm initial pain.

Rest for longer periods has not been shown to be beneficial and can cause deconditioning, loss of bone density, decreased intradiskal nutrition, loss of muscle strength and flexibility, and increased segmental stiffness.

Passive modalities are valuable during the initial 48 hours of relative rest to aid in pain relief, but protracted courses of passive treatments become counterproductive, as they place patient in a dependent role instead of an active one.

Education is one of the most important components of any back-care program and should include an explanation of the natural history of acute, subacute, and chronic disk injury.

The physical rehabilitation program should also include training in proper body mechanics and lumber ergonomics during various functional, occupational, and avocational activities.

Manual techniques may be applied to increase soft tissue pliability when secondary myofascial tightness is present. If the aforementioned measures are appropriate and completed, an active, dynamic rehabilitation program to stabilize the lumbar spine may be started on an outpatient basis.

In addition, rehabilitation of other associated components of the functional kinetic chain may be appropriate, as these structures may also be affected.

Dynamic lumbar-spine stabilization programs are aimed at maintaining a neutral spine position throughout various daily activities. An extension bias commonly is used to help reduce intradiscal pressure. This position allows for balanced segmental force distribution between the disk and zygapophyseal joints, it provides functional stability with axial loading to help minimize the chance for acute dynamic overload upon the disks, it minimizes tension on ligaments and fascia planes, and it decreases symptoms.

Repetition is key to increasing flexibility, building endurance, and developing the required muscle motor engrams that subconsciously activate a series of key multimuscular contractions to maintain the lumbar spine in a neutral position throughout static and dynamic activities.

For athletes, the aforementioned program can be progressively combined with sport-specific plyometrics to help the lumbar spine maintain neutral position during high-intensity, unpredictable, reaction-intensive sports.

Rehabilitation of athletes should also train them to maintain a neutral spine position in sport-specific motions. These component motions should then be grouped into a new, safe spine-stable movement.

Cardiovascular training is an important adjunct to comprehensive rehabilitation programs because it provides endurance necessary to prevent fatigue of the muscles that stabilize the spine.

OCCUPATIONAL THERAPY

Occupational therapy can be an important adjunct in the rehabilitation process when generalized muscular deconditioning has created adverse effects on strength, endurance, and flexibility of the upper extremities and/or impairment in activities of daily living (ADLs).

An occupational therapist often provides this portion of the rehabilitation program. Essential elements consist of ensuring proper ergonomics at the work site, which may involve simply reconfiguring a desktop and/or workstation, or it may require complex solutions.

Another aspect involves rehabilitation before the patient resumes full-time duties. After the offending source of pain is resolved, the patient typically has deconditioning and may require activity-specific reconditioning to prevent new or recurring injury.

RECREATIONAL THERAPY

Recreation therapy may have a role in assisting the patient to resume avocational activities, possibly with adaptations in technique or with the use of adaptive equipment.

SURGICAL INTERVENTION

Available surgical approaches include anterior, posterior, or combined procedure; interbody fusion with allograft autologous bone or threaded titanium cage; and intertransverse process in situ fusion with or without instrumentation.

The introduction of disk arthroplasty has been proposed as a possible surgical option in those patients who would like to maintain as much segmental motion as possible.

• To date, no prospective randomized blind study has demonstrated the superiority of any surgical approach or technique. One retrospective study was performed to compare posterolateral fusion with iliac-crest allografting and translaminar facet-screw augmentation, anterior interbody fusion with fibula allografting, posterolateral fusion with pedicle screw-rod fixation, and anterior interbody threaded cage fusion combined with facet-joint fusion and posterolateral fusion. The results suggested that the last procedure may provide superior outcomes.

• Other investigators report outcome rates ranging from 39% to 82-93% for various procedures. With respect to disk arthroplasty, the literature is not clear on its definitive role, if any, in the treatment of symptomatic LDDD.

• In a study of 59 patients suffering from low back pain and 1- or 2-level LDDD, Freudenberger et al compared the effectiveness of anterior lumbar interbody fusion with anterior tension band plating (ALIF-ATB) with that of posterior lumbar interbody fusion (PLIF) with pedicle screw instrumentation. The investigators found that both techniques had similar fusion rates, but that patients who underwent PLIF had greater estimated blood loss and required more surgical time than did patients who were treated with ALIF-ATB.

MEDICATION

Medications are an integral part of treatment of LDDD. A myriad of medications of various subtypes has been prescribed by a wide array of medical specialties to help patients with sequelae of LDDD.

Several types of medications may be helpful in treatment of diskogenic pain (eg, analgesics [peripheral and centrally acting], muscle relaxants, sedatives, glucocorticoids, anticonvulsants, antidepressants, antihistamines, stimulants). Mainstays of oral treatment of LDDD, peripherally acting analgesics, are discussed here.

Analgesics act either peripherally or centrally.

Peripherally acting analgesics include nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen.

NSAIDs are the drugs of choice (DOCs) in initial pharmacologic treatment of acute episodes of diskogenic pain or with acute exacerbation of chronic diskogenic pain. NSAIDs have mild-to-moderate analgesic, antipyretic, and anti-inflammatory properties.

NSAIDs have multiple mechanisms of action, including inhibition of cyclo-oxygenase, competition with prostaglandin at receptor sites, and inhibition of WBC migration and of lysosomal enzymes from WBCs.

Analgesic effect appears earlier and at lower doses than anti-inflammatory effects. Increasing dosage usually increases analgesic effect, with a ceiling effect after which increasing dosages do not increase therapeutic efficacy but do increase toxicity. Use of these medications on a long-term basis is not advised. For reasons not well understood, some patients respond to some NSAIDs and not to others despite their apparently similar mechanisms of action.

This response does not correlate with the class of NSAIDs. Therefore, 7- to 14-day trials of up to 3 different NSAIDs should be performed before one deems NSAIDs ineffective for an individual patient.

NSAIDs can be divided into categories based on the cyclo-oxygenase (COX-2) specificity and short, intermediate, or long half-lives. COX-2 specific NSAIDs are primarily beneficial because they do not inhibit the COX-1 isoenzyme. This property dramatically decreases risk of GI and renal adverse effects.

NSAIDs with a short half-life (4-6 h) include aspirin, ibuprofen, ketoprofen, and flurbiprofen. Of these medications, aspirin and ibuprofen are the DOCs. NSAIDS with an intermediate half-life (8-12 h) include naproxen, etodolac, diclofenac, sulindac, and diflunisal. Of these, naproxen

Ketoralac requires special consideration because it is the NSAID best known for its analgesic effect at the opioid level. However, it should be used for a maximum of 5 days (in any form). Acetaminophen is effective for mild to moderate pain. It has analgesic and antipyretic properties but no anti-inflammatory action.

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

These drugs have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclo-oxygenase activity and prostaglandin synthesis.

They may have other mechanisms as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.

ASPIRIN (Anacin, Bayer Aspirin, Ascriptin)

Best-known NSAID; widely available; cardioprotective, cerebroprotective, and anticoagulation properties. Treats mild to moderate pain. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.

Adult: 650 mg PO q6h; not to exceed 3 g/d

Pediatric: 90-130 mg/kg/d PO divided q6h with target plasma salicylate level of 150-300 mcg/mL

IBUPROFEN (Ibuprin, Motrin)

DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Adult: 400 mg PO q4-6h; not to exceed 2400 mg/d 

Pediatric: <6 months: Not established

6 months to 12 years: 10 mg/kg PO q6-8h; not to exceed 40 mg/kg

>12 years: Administer as in adults

NAPROXEN (Naprelan, Naprosyn, Aleve)

For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, decreasing prostaglandin synthesis.

Adult: 250, 375, or 500 mg PO bid; not to exceed 1500 mg/d 

Pediatric: <2 years: Not established

>2 years: 5 mg/kg PO bid

NABUMETONE (Relafen)

Nonacidic NSAID rapidly metabolized after absorption to a major active metabolite that inhibits cyclooxygenase enzyme, which inhibits pain and inflammation.

Adult: 1000 mg/d PO; not to exceed 1000 mg PO bid

KETOROLAC (Toradol)

Inhibits prostaglandin synthesis by decreasing activity enzyme, cyclo-oxygenase, decreasing formation of prostaglandin precursors.

Adult: <65 years: 60 mg IM initially followed by 15-30 mg q6h prn; not to exceed 5 d of treatment

>65 years: 30 mg IM initially followed by 15 mg q6h prn; not to exceed 5 d of treatment

CELECOXIB (Celebrex)

Primarily inhibits COX-2. COX-2 is considered an inducible isoenzyme, induced by pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity.

At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, incidence of GI toxicity, such as endoscopic peptic ulcers, bleeding ulcers, perforations, and obstructions, may be decreased when compared with nonselective NSAIDs. Seek lowest dose for each patient.

Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).

Has a sulfonamide chain and is primarily dependent upon cytochrome P450 enzymes (a hepatic enzyme) for metabolism.

Adult: 200 mg/d PO qd; alternatively, 100 mg PO bid 

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause fluid retention and peripheral edema; caution in compromised cardiac function, hypertension, conditions predisposing to fluid retention; caution in severe heart failure and hyponatremia because may deteriorate circulatory hemodynamics; NSAIDs may mask usual signs of infection; caution in the presence of existing controlled infections; evaluate therapy when symptoms or lab results suggest liver dysfunction

ANALGESICS

Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who experience pain.

ACETAMINOPHEN (Tylenol, Aspirin Free Anacin, Feverall)

Ensures patient comfort, promotes pulmonary toilet, and has sedating properties.

Adult: 1000 mg PO q4-6h prn; not to exceed 4000 mg/d 

Pediatric: <6 years: Not established

6-12 years: 325 mg PO q4-6h; not to exceed 1625 mg/d

>12 years: Administer as in adults 

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hepatotoxicity possible in chronic alcoholism following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; present in many OTC products, and combined use may result in cumulative doses exceeding recommended maximum

SKELETAL MUSCLE RELAXANTS

These drugs are effective in reducing morbidity. Their mechanism of action not clearly understood.

ORPHENADRINE (Norflex)

Although the exact mode of action not well understood, has clinical effectiveness in muscular injury. Effectiveness may be related to analgesic properties. May have atropinelike effects and analgesic properties.

Adult: 100 mg PO bid

60 mg IV/IM q12h 

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiac arrhythmias and congestive heart failure

CYCLOBENZAPRINE (Flexeril)

Acts centrally and reduces motor activity of tonic somatic origins, influencing both alpha and gamma motor neurons. Structurally related to tricyclic antidepressants.

Skeletal muscle relaxants have modest short-term benefit as adjunctive therapy for nociceptive pain associated with muscle strains and, used intermittently, for diffuse and certain regional chronic pain syndromes.

Long-term improvement over placebo has not been established. Often produces a "hangover" effect, which can be minimized by taking the nighttime dose 2-3 h before going to sleep.

Adult: 10 mg PO tid with a range of 20-40 mg/d in divided doses; not to exceed 60 mg/d.