obs-22_intervertebra disk aging degeneration & herniation

Chapter 22

Intervertebral DiskAging, Degeneration,and Herniation

Chapter 22

Intervertebral DiskAging, Degeneration,and HerniationJoseph A. Buckwalter, MS, MD

Scott D. Boden, MD

David R. Eyre, PhD

Van C. Mow, PhD

Mark Weidenbaum, MD

This chapter at a glanceThis chapter discusses age-related deterioration, degenerative disease,and herniation of the intervertebral disk.

Chapter Outline

Introduction

Disk AgingNewbornChildhood and AdolescenceAdultElderly

DegenerationMechanisms of Intervertebral Disk Degeneration

Alterations in Disk Mechanical Properties

Intervertebral Disk Degeneration and Pain

HerniationMechanisms of Intervertebral Disk Herniation

Intervertebral Disk Herniation and Pain

Summary

Selected Bibliography

IntroductionNo component of the musculoskeletal system changesmore with age than the intervertebral disk. Age-relateddeterioration of disk structure, composition, and functioncontribute to the 2 most common clinical disorders of theaxial skeleton: degenerative disease of the spine and inter-vertebral disk herniation.

Once skeletal maturity is achieved, all intervertebral disksundergo progressive alterations in biomechanical proper-ties, volume, shape, microstructure, and composition thatcan decrease motion of and adversely affect the mechanicalproperties of the spine. In addition, some intervertebraldisks undergo a severe age-related loss of structure andfunction that is best considered a form of degeneration,leaving only a thin layer of fibrous tissue separating the ver-tebral bodies. Motion between adjacent vertebral bodies isrestricted, and degenerative changes in the facet joints mayoccur or worsen. In addition to restricted motion, degener-ative disease of the spine can cause pain; neurologicdeficits may occur when osteophytes compress the spinalcord or spinal nerves. The disk tissue is weakened and thereis an increased risk of herniation, which also can cause painand neurologic deficits.

Disk AgingThe changes in disk volume and shape (including loss ofdisk height, protrusion of the central disk into the vertebralbody with a decrease in the height of the anulus, and buck-ling or bulging of the anulus) and the rate at which thesechanges occur following skeletal maturity vary among indi-viduals and among disks. Unfortunately, these changeshave not been well defined or correlated with those in disktissue structure and composition.

Changes in disk tissue microstructure and compositionprecede and accompany the alterations in gross morpholo-gy. The changes in disk size, vascular supply, and composi-tion (especially proteoglycan organization and proteogly-can and water concentrations) begin during growth anddevelopment, well before evidence of disk degenerationappears. These early changes may form the basis for thechanges that occur following skeletal maturity, includingdegeneration. In this sense, the age-related disk changesbegin soon after birth. The most extensive changes occur,after age 20, in the nucleus pulposus, where there is adecline in the number of viable cells and the concentra-tions of proteoglycans and water. These changes areaccompanied by fragmentation of the aggregating proteo-glycans and increases in the concentrations of collagensand noncollagenous proteins.

Newborn

At birth, distinct hyaline cartilage end plates separate thedisk tissues from the vertebral bodies. The outer anulusfibrosus consists of dense circumferential layers of collagenfibrils (Fig. 1) that penetrate the cartilage plates of the ver-tebrae. Occasional elastic fibers lie parallel to the collagenfibrils. Small blood vessels may be found between the outerlamellae of the anulus fibrosus, especially in the posterolat-eral regions of the disk and adjacent to the cartilage endplates, and occasional blood vessels penetrate the inneranulus. Numerous perivascular and free nerve endings lieon and among the most peripheral layers of the anulus. Thenucleus pulposus fills almost half the disk and at birth con-sists primarily of notochordal tissue: a soft, gelatinous, clearmatrix surrounding syncytial cords and clusters of noto-chordal cells. The matrix of the nucleus contains few colla-gen fibrils and even fewer sheets of elastin embedded in anabundant network of highly hydrated proteoglycans. Indisk tissues of the newborn, collagen fibers have a nearlyuniform small diameter (Fig. 1). Proteoglycan aggregatesfrom newborn and infant intervertebral disk anulus fibro-sus and cartilage end plate have the same structure asaggregates from hyaline cartilages; only about one third ofnucleus pulposus proteoglycan aggregates resemble theselarge aggregates, and the other two thirds consist of aggre-can clusters that frequently lack a visible central hyaluro-nan filament.

Childhood and AdolescenceDuring skeletal growth, disk volume and diameter increaseseveral fold, thereby increasing the distance between thecentral regions of the disk and the peripheral blood vessels.At the same time the blood vessels of the anulus and thecartilage end plate become smaller and less numerous. Thefibrocartilaginous component of the anulus increases insize, but during early adolescence the nucleus pulposus stillcomprises nearly half the disk and can easily be distin-guished from the fibrocartilage of the inner anulus. Thenumber of notochordal cells decreases, and chondrocyte-like cells appear in the central regions of the disk. More col-lagen fibrils appear in the nucleus, and the collagen fibrilsof all disk components increase in mean diameter and vari-ability in diameter (Fig. 1). The proportion of proteoglycansthat form aggregates and proteoglycan aggrecan size bothdecrease, and large proteoglycan aggregates similar tothose found in articular cartilage disappear. By adoles-cence, the proteoglycan population of the nucleus pulpo-sus consists almost entirely of clusters of short aggrecanmolecules and nonaggregated proteoglycans. A decline inthe concentration of functional link protein may cause atleast some of the change in proteoglycan aggregates.

558 Section 2 Tissues and Pathophysiology

Orthopaedic Basic Science American Academy of Orthopaedic Surgeons

Chapter 22 Intervertebral Disk Aging, Degeneration, and Herniation 559

Adult

With skeletal maturity, many of the remaining peripheralblood vessels disappear. The size of the outer anulus fibro-sus stays about the same, but the apparent size of the fibro-cartilaginous inner anulus expands at the expense of thenucleus pulposus as the latter becomes progressively morefibrotic. In portions of the anulus, myxomatous degenera-tion develops with loss of the normal collagen fiber organi-zation. Fissures and cracks appear in the disk, oftenbetween the lamellae, and extend from the periphery tothe central regions. The nucleus pulposus becomes firmand white rather than soft and translucent. In all regions ofthe disk inside the outer anulus, but especially in the mostcentral regions, the concentration of viable cells declinessharply. Few if any notochordal cells remain, but the cen-tral regions of the nucleus contain scattered viable chon-drocyte-like cells. Proteoglycan and water concentrationsdecrease and collagen and noncollagenous protein con-centrations increase as dense granular material accumu-lates throughout the matrix (Fig. 1). Although this materialappears throughout the matrix, it appears especially con-centrated in the regions immediately surrounding the cellsand forms thick sheaths around some collagen fibers. Itscomposition remains unknown, but it may containdegraded matrix molecules or noncollagenous matrix pro-teins including fibronectin, and its deposition in thematrix may be at least partially responsible for the age-related increase in the concentration of noncollagenousprotein. Taken together, the age-related alterations in disktissue following skeletal maturity appear to decrease thestructural integrity of the disk and thereby contribute tothe changes in disk volume and shape and the increasedprobability of mechanical failure of the matrix leading todisk herniation.

ElderlyIn the elderly, the entire disk inside the outer lamellae ofthe anulus fibrosus usually becomes a stiff fibrocartilage. Itmay be difficult if not impossible to distinguish the inneranulus fibrosus from the nucleus pulposus by gross exam-ination, although the region of the nucleus may still haveless densely packed collagen fibrils of smaller diameter, asdemonstrated by electron microscopy. In the centralregions of the disk, few viable cells remain (Fig. 2). Theheight of the disk may decline further and prominent fissures and clefts may form in the center. The loss of diskheight and alterations in disk composition can affect spinemobility and alter the alignment and loads (vector) appliedto the facet joints, spinal ligaments, and paraspinousmuscles.

Electron micrographs showing collagen fibrils from the anulus fibrosus. A,Newborn. B, Young adult. C, Older adult. Note that the mean collagen fibrildiameter and the variability in collagen fibril diameter increase betweenbirth and skeletal maturity and that with age, electron-dense granular mate-rial accumulates in the matrix. (Reproduced with permission from Buckwal-ter JA: The fine structure of human intervertebral disk, in White AA III, Gordon SL (eds): American Academy of Orthopaedic Surgeons Symposium onIdiopathic Low Back Pain. St. Louis, MO, CV Mosby, 1982, pp 108–143.)

Figure 1

American Academy of Orthopaedic Surgeons Orthopaedic Basic Science

A

B

C

DegenerationAlthough all disks undergo aging changes, not all of themdegenerate. Disks that have almost disappeared, leavingonly a thin layer of fibrotic tissue separating adjacent verte-bral bodies, represent the end stage of the degenerativeprocess (Fig. 3). In many instances advanced disk degener-ation is associated with vertebral body osteophytes,increased bone density or sclerosis of the vertebral bodiesadjacent to the disk, and facet joint osteoarthritis (Fig. 4).Small blood vessels proliferate in the end plates and verte-bral bodies and grow into the peripheral regions of degen-erated disks. Extension of nerves into the inner regions ofthe disk may accompany this vascular proliferation andingrowth, and several investigators have found evidencethat these changes are associated with back pain. The lossof disk tissue results from the action of degradativeenzymes within the disk and the inability of disk cells tomaintain or restore their extracellular matrix. This last stageof disk degeneration leads to a loss of spinal mobility andabnormal loading of the facet joints, spinal ligaments, andmuscles. The relationships between disk degeneration andclinical disorders of the spine are complex. Advanced diskdegeneration is commonly found in middle-aged and olderpeople with no symptoms, but in others it can lead to spinalstenosis and neurogenic claudication as well as back pain.

Although the end stage of intervertebral disk degenera-tion can be identified by imaging studies and gross exami-nation, widely accepted criteria for the diagnosis of diskdegeneration and for distinguishing between disk agingand degeneration have not been established. Correlation ofchanges in disk size, shape, composition, and mechanicalproperties with alterations in spine function may make itpossible to develop these criteria. These types of studieshave recently been reported in the literature, and mayeventually show that disk degeneration differs from thenormal aging of the disk, much like osteoarthritis or degen-erative joint disease differs from normal aging of synovialjoints. In both synovial joints and the joints formed by



Electron micrograph showing the remains of a necrotic nucleus pulposuscell. V indicates membrane-bound vacuoles and the arrows mark dense celldebris. (Reproduced with permission from Buckwalter JA, Martin J: Inter-vertebral disk degeneration and back pain, in Weinstein JN, Gordon SL(eds): Low Back Pain: A Scientific and Clinical Overview. Rosemont, IL,American Academy of Orthopaedic Surgeons, 1996, pp 607–623.)

Figure 2

Radiograph showing advanced degen-eration of an intervertebral disk. Notethe almost complete loss of diskheight and the formation of vertebralosteophytes. (Reproduced with per-mission from Buckwalter JA, Martin J:Intervertebral disk degeneration andback pain, in Weinstein JN, Gordon SL(eds): Low Back Pain: A Scientific andClinical Overview. Rosemont, IL,American Academy of OrthopaedicSurgeons, 1996, pp 607–623.)

Figure 3

vertebral bodies and intervertebral disks, degenerativechanges may or may not be associated with pain. Articularcartilage and intervertebral disks change with age, anddegeneration of both these tissues is closely correlated withincreasing age, but despite aging changes these tissues con-tinue to function well throughout life in many individuals.Thus, disk degeneration may result from either an acceler-ation or exacerbation of normal aging or a distinct processthat is superimposed on normal aging; at present a distinc-tion between these 2 alternatives cannot be made.

Mechanisms of Intervertebral Disk DegenerationA variety of mechanisms, including declining nutrient andwaste product transport mechanisms (for example, loss ofthe cartilage end plate and decreased tissue hydration)decreasing concentration of viable cells, cell senescence,apoptotic debris, loss of aggregating proteoglycans, modifi-cation of matrix proteins, degradative enzyme activity,accumulation of degraded matrix macromolecules, andfatigue failure of the matrix, may contribute to disk degener-ation. Although each of these mechanisms may alter diskcomposition and microstructure, their relative importanceand the interactions among them have not been established.

Declining nutritional transport appears to be the mostcritical event responsible for the changes in central diskcells and their matrices. The disk cells rely on diffusion andconvection of nutrient waste products through the matrixfrom blood vessels on the periphery of the anulus fibrosusand within the vertebral bodies. The increase in disk vol-ume during growth, combined with the progressive age-related decline in the number of arteries supplying theperiphery of the disk (and possibly calcification of the car-tilage end plates), impair delivery of nutrients and removalof waste products. At the same time the blood supply to theperiphery of the disk declines, the accumulation of degrad-ed matrix macromolecules and decreasing matrix waterconcentration within the central disk may interfere withdiffusion and convection through the matrix, further com-promising cell nutrition.

Not only does the supply of nutrients decline, but the pHis decreased. This decrease is caused by a rise in lactateconcentration due to an increase in its production as aresult of low oxygen tension and decreased rate of lactateremoval. A lower pH compromises cell metabolism andbiosynthetic functions and can cause cell death. Factorsthat may increase the rate and severity of age-relatedchanges in the intervertebral disk by indirectly alteringnutrition transport include increased disk loading due todemanding physical activities, immobilization, vibration(such as while driving), or spinal deformity. Factors thatdirectly compromise the vascular supply include smoking,vascular disease, and diabetes.

The age-related decline in nutrition and waste transportto and from the central disk region and the accompanyingdecline in pH would be expected to have an adverse effecton cell viability. Indeed, electron microscopic studies showthat the proportion of necrotic cells and apoptotic debrisincreases with age. In fetal and infant intervertebral disks,no more than 2% of the nucleus pulposus cells showedmorphologic signs of necrosis. In disks of some adolescentsand young adults, more than 50% of the nucleus cells werenecrotic, and in samples from elderly people, more than80% were necrotic.

Although age-related changes in disk cell function havenot been extensively studied, in other tissues declining cellfunction contributes to age-related degeneration. Evenwithout decreased cell nutrition, many normal differentiat-ed cells become senescent with age. The cells remain viable,but lose their capacity to replicate DNA and possibly someor all of their synthetic capacity and other specialized func-tions. Experimental evidence suggests that these alter-ations in cell capacity result from changes in gene expres-sion, and that these age-related changes are controlled bytranscription factors, proteins that bind to specificsequences of DNA and direct gene expression.

Mature intervertebral disks lack large proteoglycan aggre-gates and aggrecans similar to those found in articular car-tilage. The available evidence suggests that a population of



Drawing showing degenerative changes of the spine. Notice the advanceddegeneration of the L4-5 and L5-S1 intervertebral disks, the formation ofvertebral and facet joint osteophytes, and the narrowing of the interver-tebral foramina by the osteophytes.

Figure 4

articular cartilage-like proteoglycan aggregates exists in thedisks of newborns, but disappears during maturation andthat the aggrecans become shorter. Other work shows thata decline in proteoglycan concentration precedes andaccompanies disk degeneration. The loss of proteoglycanaggregates and large aggrecans and decreased proteoglycanconcentration affect the ability of the disk to maintain ahigh water concentration (see Chapter 21). These changes,combined with the increasing collagen concentration and adecline in water concentration, make the central diskfibrotic and stiff, and decrease its ability to maintain itsheight and distribute loads.

With increasing age, connective tissue matrices, includingthose of the intervertebral disk tissues, tend to lose elastic-ity and strength. These changes may result from modifica-tions of the various matrix collagen molecular form andultrastructural organization. These alterations, includingincreased collagen cross-linking, impaired collagen fibrilformation, and denaturation of collagen, contribute to diskdegeneration. Increasing collagen cross-links throughnonenzymatic glycation or lipid peroxidation may cause anincrease in brown pigmentation with age, and, more impor-tantly, alter disk mechanical properties. In addition to theirpotential effects on tissue biomechanical properties, glyca-tion products also can stimulate cells, including chondro-cytes, to release cytokines and proteases that contribute totissue degeneration. Examination of adult human interver-tebral disks has shown greater denaturation of type II colla-gen (loss of triple helical configuration) in the anulus fibro-sus and nucleus pulposus than in articular cartilage fromthe same individuals. This difference may result from accu-mulation of degraded molecules in the intervertebral diskand could alter the biomechanical properties of the colla-gen fibrillar framework and the interaction of type II colla-gen fibrils with other matrix molecules.

Throughout life newly synthesized matrix moleculesreplace older molecules that are enzymatically degraded.An imbalance between synthesis and degradation leads to aloss of disk tissue. The cause of the imbalance between syn-thetic and degradative activity in degenerating disksremains unknown.

With aging, accumulation of partially degraded moleculesmay alter the properties of the disk, including the biome-chanical behavior of the tissue and the ability of nutrientsand metabolites to diffuse and convect through the matrix.Increasing concentrations of degraded molecules, and pos-sibly noncollagenous proteins, may inhibit or interfere withthe ability of cells to synthesize new molecules. Accumula-tion of degraded molecules may also interfere with thetransport and assembly of newly synthesized molecules inthe matrix. For example, accumulation of hyaluronan bind-ing fragments of proteoglycan aggrecan core proteins mayinterfere with assembly of proteoglycan aggregates.

Normal spine movement requires loading and deforma-tion of disks followed by recovery of disk shape. In addition,

maintaining an upright posture decreases disk height bydriving water out of the disk matrix. Prolonged recumben-cy then restores the original disk shape and volume aswater returns to the matrix. These repetitive deformationsof the disk may lead to fatigue failure of the collagen fibers,and anulus delamination. These failures may appear asmacroscopically observable fissures, cracks, or myxoiddegeneration (appearance and accumulation of myxoidmaterial within dense fibrous tissue), or as more subtlechanges in the macromolecular framework of the matrixincluding fragmentation of proteoglycans, and disruptionof collagen fibrils and the relationships between the colla-gen network and other matrix macromolecules. Thesealterations of the matrix may expose cells to increasedstresses and strains that compromise their function.

Age-related changes in the disk may lessen the ability ofthe tissue to recover from deformation, either from a loss ofintrinsic elasticity of the solid matrix or from a decrease ofthe Donnan osmotic pressure resulting from the loss of pro-teoglycans, and make it more vulnerable to progressivemicrodamage of the matrix. Loss of proteoglycans andwater from the central disk regions (that is, decreased fluidpressure load support from loss of hydrostatic or osmoticpressures, or both) would therefore necessarily increase theloads that the collagen-proteoglycan solid matrix mustcarry. Modifications of the collagens, decreased water con-centration, and accumulation of degraded matrix mole-cules may make the collagen framework more vulnerable tofurther mechanical failures, either fatigue or rupture. Also,the decline in cell nutrition, decreased concentration ofviable cells, and cell senescence, combined with the accu-mulation of disorganized molecular debris in the extracel-lular matrix, could further compromise the ability of thecells to repair the altered organization of the degeneratedmatrix. This repair process must necessarily depend on thetransport of these matrix molecules once the cells havemade and extruded them into the interterritorial space. Anyhindrance of this transport process clearly will affect extra-cellular matrix repair.

Alterations in Disk Mechanical PropertiesThe changes in composition and structure that occur withaging and degeneration alter the mechanical properties ofthe disk. The most apparent changes include increaseddeformability, decreased intradiskal hydrostatic andosmotic pressure, reduced fatigue life and failure strength,altered manner of load support Chydrostatic pressure ver-sus osmotic pressure versus matrix stresses, and changes intheir biphasic viscoelastic properties. The normal nucleuspulposus behaves in a manner similar to a viscous fluid;with degeneration, it shows an increase in shear modulus(becomes stiffer) and becomes more elastic. This undoubt-edly is the result of a shift of composition of the nucleus



with increasing collagen content. This shift in compositionhas been shown to increase tissue stiffness, decrease dissi-pation, and result in more elastic solid-like behavior. Thistransition from fluid-like to more solid-like behavior isassociated with a decrease in hydrostatic pressurization,resulting in reduced energy dissipation in the disk. Thismay lead to significantly altered states of stress in the disk,with focal areas of abnormally high stresses and strains inboth the nucleus pulposus and anulus fibrosus. The loss ofa fluid-like nature suggests a loss of the isotropic stress statein the nucleus pulposus. The maintenance of a fluid-likenature is critical to the ability of the tissue to distributeloads. This mechanical change is likely to result in anincrease in the anisotropic and nonuniform deformationalbehaviors of the entire disk and may be partly responsiblefor the induction of focal or site-specific damage in thedisk. This modified stress-strain environment may havedeleterious effects on the entire disk and may contribute tocommonly observed degenerative changes such as tearingof the anulus fibrosus.

Anulus fibrosus samples with degenerative changes donot exhibit the same degree of anisotropy in compressionas in tension. Significant effects of degeneration or speci-men orientation on permeability have not been noted inanulus fibrosus samples with degenerative changes,although significant effects on stress and compressive stiff-ness have been identified. This implies that the highly orga-nized anulus fibrosus collagen network does not play themajor role in compression that it does in tension. Normal-ly, fluid pressurization and osmotic swelling pressure shieldthe solid matrix from large stress and strains. With degen-eration there is a loss of fluid content and thus fluid pres-surization. This means that more of the load must now becarried by nonhydrostatic (and nonuniform) mechanisms.This diminution of stress shielding of the collagen-proteo-glycan solid matrix is thought to be a major determiningfactor in disk degeneration.

Permeability is orientation-dependent (anisotropic) foranulus fibrosus specimens without degenerative changes,but not for those with degenerative changes. In anulusfibrosus samples without degenerative changes, perme-ability is greatest in the radial direction (important in diffu-sion and convective fluid transport of nutrients). Withdegeneration, radial permeability decreases (due todecreased water content or clogging of the pores with mol-ecular debris) while axial and circumferential permeabilityincrease (due to structural changes such as fissuringbetween the lamellae), leading to more isotropic perme-ability. This pattern is consistent with streaming potentialbehavior as well. Reduction of steady-state streamingpotentials with degeneration may be caused by a decreasein proteoglycan content (that is, decrease of the fixedchange density) with disk degeneration.

Degeneration not only affects the nucleus pulposus andanulus fibrosus, but it affects the end plate as well. Thin-

ning, microfracture, or damage to the end plate with degen-eration may significantly increase its hydraulic permeabili-ty, allowing rapid fluid exudation from the cartilage endplate on loading. Although beneficial for nutrient transport,this rapid fluid exudation would defeat any hydrostaticpressure load-support mechanism provided by the endplate, leading to a more nonuniform load distributionacross the entire disk and higher shear stresses, thus con-tributing to site-specific damage in the disk.

With this understanding of disk mechanics, it is clear thatchanges with degeneration in the material behaviors of diskcomponents may predispose the disk to mechanical failure.This can occur in the absence of any change in the type, fre-quency, or magnitude of loading. Degeneration is the nat-ural consequence of either of 2 scenarios: (1) application ofnormal loads to disk components with abnormal materialproperties; and (2) application of abnormal loads to components with normal material properties. In traumaticsituations, the latter scenario would prevail.

It appears that the degenerative process affects the nucle-us pulposus and cartilage end plate more significantly thanthe anulus fibrosus, at least with respect to changes inmaterial properties. A scenario is therefore suggested inwhich loss of hydrostatic pressurization and osmotic pres-sure in both the nucleus pulposus and cartilage end platewith degeneration has a deleterious effect on the entiredisk. The loss of the mechanism for uniform load transferand the loss of the isotropic pressure load support in thenucleus pulposus and cartilage end plate seem to lead tostates of nonuniform stress within the anulus fibrosus,resulting in the development of focal stress concentrationsand high shear stresses, and thus material failures.

Reduction of steady-state streaming potential with degen-eration is due to the decrease in proteoglycan content (fixedcharge density) with degeneration along with changes inother material properties (such as stiffness or permeability).These results may provide insight into such phenomenon assignal transduction to cells to modulate their metabolicactivities. Changes in the streaming potential response ofthe disk suggest the possibility of developing sensitive meth-ods for detecting early disk degeneration using electro-mechanically instrumented arthroscopic probes.

Intervertebral Disk Degeneration and PainThe relationships between disk degeneration and painremain poorly understood. Some individuals with minimalmorphologic evidence of disk degeneration have chronicback pain and stiffness, while others with advanced diskdegeneration have minimal symptoms. Yet, the availableinformation suggests that intervertebral disk degenerationmay contribute to back pain through 3 possible mecha-nisms: loss of disk structure and biomechanical properties,release of mediators that may sensitize nerve endings, and



nerve and blood vessel ingrowth into degenerated disks.The loss of disk structure and biomechanical propertiesalters loading and alignment of vertebral bodies, facetjoints, spinal ligaments, and muscles, and decreases theability of the disks to absorb and distribute loads applied tothe spine (Fig. 4). These changes may increase stimulationof nerve endings in bone, spinal ligaments, facet joint cap-sules, and muscles. By altering the biomechanical functionof the spine and the alignment of the facet joints, long-standing advanced disk degeneration may initiate or accel-erate development of osteoarthritis of the facet joints.

In addition to these structural and loading changes, thecell and matrix changes associated with disk degeneration,including cell necrosis, may be associated with release ofcytokines, free radicals, and other molecular debris frommatrix degradation. Some of these substances can sensitizenociceptive nerve endings and thereby contribute to thedevelopment of back pain. Although normal intervertebraldisks rarely have nerve fibers or blood vessels that penetratefurther than the first lamellae of the outer anulus, nervesand blood vessels have been identified in the inner anulusand even in the nucleus pulposus of degenerated disks, andthese changes have been correlated with back pain.

HerniationIntervertebral disk herniation refers to protrusion of tissuefrom the nucleus pulposus through a defect in the anulusfibrosus (Fig. 5). The herniated tissue may remain attachedto the disk or become a free fragment. This material mayfrequently impinge on the spinal nerves, causing back pain.

Mechanisms of Intervertebral Disk HerniationFissures that extend through the full thickness of the anulusfibrosus create a defect that will allow herniation of nucle-us pulposus tissue. Experimentally, compressive loadsapplied to flexed, twisted, fully saturated disks cause prop-agation of annular fissures, most often starting at the junc-tion of the posterior anulus and the vertebral body. Thecauses of annular fissures in vivo remain poorly under-stood, but the fissures are presumed to result from localizeddegeneration of the anulus fibrosus or from excessive load-ing of normal annular tissue. It is also not clear how oftenfull-thickness fissures lead to disk herniation; however,once the fissures form, the risk of herniation exists. Becauseprolonged recumbence allows fluid to flow into the centraldisk, increasing hydrostatic pressure and in some instancesdisk volume, many disk herniations occur in the morning,soon after the patients increase disk loading by assumingan upright posture. The most common site of annular dis-ruption and symptomatic disk herniation is at the insertionof the outer anulus into the vertebral body. Hence, herniat-ed tissue commonly tracks from the posterior surface of theanulus near its bony insertion into the space between theanterior surface of the posterior longitudinal ligament andthe posterior surfaces of the anulus and vertebral body andthen cephalad or caudad into the spinal canal.

Intervertebral Disk Herniation and PainClinical studies show that the relationships between inter-vertebral disk herniation and pain are complicated. Insome patients, back pain precedes a disk herniation, and


Magnetic resonance images showing herniated intervertebral disks. A, Sagittal view showing posterior herniation of the L5-S1 intervertebral disk. Notethat the L4-5 intervertebral disk has a well-defined nucleus pulposus, but the L5-S1 disk has a poorly defined nucleus pulposus and reactive changes inthe vertebral end plates suggesting the presence of degenerative changes. B, Transverse view showing a posterior lateral herniation of the L5-S1 inter-vertebral disk.

Figure 5


A B

when the herniation occurs the back pain decreases. Otherpatients have no prodromal symptoms. Once herniationoccurs, mechanical pressure and chemical irritation fromthe extruded nucleus pulposus tissue are presumed tocause the pain in the region of the affected nerve root orroots. In more than 90% of patients with symptomatic diskherniations, the pain subsides within 3 months. In manypeople (28% to 35% of asymptomatic patients), disk herni-ations occur in the absence of symptoms.

SummaryThe common clinical problems of degenerative disease ofthe spine and intervertebral disk herniation may resultfrom degenerative changes in the disk. Mechanisms thatappear to contribute to disk degeneration include decliningnutrition to the cells, decreasing concentration of viablecells, cell senescence, loss of aggregating proteoglycans,modification of matrix proteins, degradative enzyme activ-ity, accumulation of degraded matrix macromolecules, andfatigue and other mechanical failures in the matrix. Also,changes in load support from fluid pressurization, chydro-static and osmotic, to matrix compression can further exac-erbate the matrix damage. The most important initiatingmechanism for disk degeneration, however, appears to bedeclining nutrition to the cells, thus permitting damageaccumulation to occur in the disk. Demanding physicalactivities, immobilization, vibration, spinal deformity,smoking, vascular disease, and diabetes can accelerate thedecline in disk nutrition. Disk degeneration may cause painby contributing to the development of facet joint osteo-arthritis and spinal stenosis, by releasing mediators thatsensitize nociceptive nerve endings, and by stimulatingproliferation and ingrowth of blood vessels and nervefibers. Disk herniation results from a rupture of the anulusfibrosus that allows central disk material to protrudethrough a defect in the anulus fibrosus. Herniations maycause pain and neurologic deficits by stimulating inflam-mation of adjacent tissues and by placing pressure on thespinal cord or nerve roots.

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