Techniques in Regional Anesthesia and Pain Management (2009) 13, 67-75

Anatomy and pathophysiology of intervertebral disc

disease
Hariharan Shankar, MBBS,a,b Jeremy A. Scarlett, MD,b Stephen E. Abram, MDb
From the aDepartment of Anesthesiology, Clement Zablocki VA Medical Center, Milwaukee, Wisconsin; and the
b
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
KEYWORDS:
Intervertebral disc;
Anatomy and
histology;
Physiopathology;
Blood supply;
Innervation;
Herniated disc

Intervertebral discs provide support and cushioning against mechanical loads. Changes secondary to aging
and degeneration lead to loss of this important function. This also sets the stage in some for disc-related pain.
Various therapeutic modalities have been attempted with minimal long-term success to alleviate the poorly
described disc-related pain. To better understand the pain originating from the disc, this article attempts to
explore the anatomy of the disc and the different perturbations that occur following aging and degeneration.
There is a great deal of similarity among the discs in different levels. They all consist of a nucleus pulposus,
surrounded by the annulus fibrosus, whose outer layers integrate with the endplate and the ligaments to
strengthen and provide support. The spinal arteries provide the nutrient supply, and the lack thereof seems
to be a hallmark of degeneration and aging. The nerve supply is provided by the sympathetic chain and from
the recurrent sino vertebral nerve, but only the outermost layers of the annulus contain the sensory nerve
fibers. There also appears to be some genetic variation in the rate and degree of synthesis and breakdown
in the primary structural components of the disc, increasing the predisposition for disc-related pain. This
review will also briefly discuss the evidence that has accumulated regarding the occurrence of such
pathologic changes from a genetic and ergonomic perspective.
Published by Elsevier Inc.

Intervertebral discs play a significant role in the support,

durability, and flexibility of the spine. While discs allow for
some movement between different spinal segments, they
provide tremendous stability of the overall spinal column in
the face of a variety of different forces and massive loads.
Disc degeneration is a relatively common problem, and its
incidence seems to increase with the aging process. Changes
consistent with disc degeneration have been identified in
teens.1 It has been shown that approximately 20% of teenage discs are already showing signs of disc degeneration
and they are nearly universal by the eighth decade.2
Although the correlation between disc degeneration and
disc-related pain is not precise, there is a known strong
Address reprint requests and correspondence: Hariharan Shankar,
MBBS, Department of Anesthesiology, Clement Zablocki VA Medical
Center, 5000 West National Avenue, Milwaukee, WI 53295.
E-mail address: hshankar@mcw.edu.

1084-208X/$ -see front matter Published by Elsevier Inc.

doi:10.1053/j.trap.2009.05.001

association between them.3,4 The prevalence rates in the UK

have ranged from as low as 12% to as high as 35%, depending on inclusion criteria. Of those patients, about 10%
develop chronic pain with disability.5 As the population of
the US continues to age, the incidence and prevalence of
pain related to disc degeneration will undoubtedly increase
and with it the economic burden on the society. Fundamental to an appropriate treatment strategy is a thorough comprehension of the disc anatomy as well as the pathophysiology and its clinical presentation.

Gross anatomy
There are a total of 23 discs in the entire length of the spinal
cord. When the height of all the discs (approximately 8-10
mm in height and 4 cm in diameter) are considered, they

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Techniques in Regional Anesthesia and Pain Management, Vol 13, No 2, April 2009

comprise approximately 25% of the total height of the

vertebral column. The centrally located nucleus pulposus is
surrounded by concentrically arranged collagen fibrils that
make up the annulus fibrosus. This, in turn, is sandwiched
between two cartilaginous endplates adjoining the vertebral
body together forming the intervertebral disc (Figure 1).
The discs are attached through cartilaginous endplates to the
vertebral body above and below6 (Figure 2).
Although there are no discs between the first two cervical
vertebra and the sacrum and coccyx, there are intervertebral
discs between the other cervical, thoracic, and lumbar vertebrae as well as between the last lumbar vertebrae and the first
sacral vertebrae. The thickness and surface area of the discs are
greatest at the lumbar levels and thinnest at the cervical levels.6
Other than variations in size and shape to meet the dimensions
of the vertebral bodies in different spinal levels, the intervertebral discs throughout the spine are remarkably similar in
composition and function. They provide the mechanical
cushion, support, and flexibility to allow the spinal column
to transmit loads from the bodys weight and muscle activ-

Figure 2 Diagram of sagittal section of vertebral body and disc

showing relationship of endplate and longitudinal ligament to the
disc and the vertebrae. 1, vertebral body; 2, annulus fibrosus; 3,
nucleus pulposus; 4, endplate; 5, spinal nerve root. (Adapted from
multiple sources, including reference 4.)

ity from the head, upper extremities, and torso to the lower
extremities. The discs play a key role in maintaining the
proper spatial orientation of the bony anatomy, such as the
vertebral bodies and facet joints, and consequently also
allow adequate room for passage of the neural roots.7

Cartilaginous endplates
The most cephalad and caudal regions of the intervertebral
discs are the cartilaginous endplates. They have approximately 1-mm-thick horizontal layer of hyaline cartilage
forming an important morphologically and functionally distinct junction between the annulus and the vertebral body.
The composition of the endplate varies slightly in the area
adjacent to the annulus. Here it is primarily composed of
collagen fibers that are continuous with the disc and lay
parallel and horizontal to the adjacent vertebral bodies;
however, the area immediately adjacent to the osseous vertebral body is made up of primarily hyaline cartilage and is
less adherent and more prone for separation during trauma.8
Early in life, the endplates are highly vascularized, but the
degree of vascularity wanes dramatically over the course of
the first year, and there are essentially no blood vessels
present by the third decade, increasing the predisposition for
degeneration.4

Figure 1 Cryo-microtome section specimen at the level of the

intervertebral disc. SP, spinous process; IAP, inferior articular
process; SAP, superior articular process; LF, ligamentum flavum;
AL, annulus fibrosus; NP, nucleus pulposus; IVD, intervertebral
disc. Black arrows represent dorsal root ganglion; white arrow
represents blood vessel.

Annulus fibrosus
The annulus is composed of a series of 15-25 lamellae, or
concentric rings of collagen. Within each lamella, the collagen fibers lie parallel and are oriented at approximately

Shankar et al

Anatomy and Pathophysiology of Intervertebral Disc

69

60 to the vertical axis. Each adjacent lamellar fiber alternates to the left and right in relation to its direction from the
vertical axis. The outermost layers of the annulus tend to be
most dense and resistant to tensile forces. These layers are
firmly attached to the endplates and the vertebral bodies and
are reinforced by the posterior and anterior longitudinal
ligaments (Figure 2). These fibers are most dense posteriorly or anteriorlaterally in close approximation to the posterior and anterior longitudinal ligaments.9,10 These outermost layers of the annulus also contain the sensory nerve
fibers.
The areas between the lamellae are filled with elastin,
which may allow the disc to return to its original position
following flexion or extension. As elastin fibers extend
radially from one lamella to the next, they may also play a
role in binding the lamellae together. The cells within the
annulus are aligned parallel to the collagen fibers. They tend
to be thin, elongated, and fibroblast-like, most notably in the
outer dense region. The annular cells tend to become more
oval as one moves inward toward the nucleus pulposus and
the collagen fibers tend to become less dense and more
loosely organized. A thin, fibrous band of tissue, referred to
as the transitional zone, surrounds the nucleus pulposus.
Thin extensive cytoplasmic projections (some greater than
30 mm) can be found in cells of both the nucleus pulposus
and the annulus. This feature is unique to the intervertebral
discs and is not found in cells of articular cartilage. The
function of these intradiscal projections remains unknown,
but it has been hypothesized that they could play a role in
the communication of mechanical strain.11

Nucleus pulposus
The nucleus pulposus differs from the annulus in that the
vast majority of it is much less dense and nearly the consistency of a gel. It contains a more solidified central region
composed of loosely organized thin, type II collagen and
irregularly shaped radially organized elastin. These hold the
gel-like area, which contains proteoglycan molecules (especially aggrecan) that have hydrophilic chondroitin and keratin sulfate attached to them. This glycoaminoglycan arrangement binds water molecules and gives the nucleus a
much higher composition of water contributing to its consistency (Figure 3). Other proteoglycans include versican,
biglycan, decorin, fibromodulin, and lumican. Other than
versican, whose function is not yet clear, and aggrecan, all
the other small proteoglycans are involved in the repair of
the extracellular matrix.12

Matrix
The extracellular matrix is composed primarily of collagen
and aggrecan. The discs collagen framework serves as an
anchor, attaching to the vertebral bodies and providing the

Figure 3 (A) Cryo-microtome section specimen at the level of

the intervertebral disc showing the degenerated nucleus. Green dye
outlining the epidural space. (B) Diagram of the intervertebral disc
with the posterior neural arch. 1, anterior longitudinal ligament; 2,
annulus fibrosus; 3, nucleus pulposus; 4, posterior longitudinal
ligament; 5, spinal roots in the dural sac; 6, vertebral canal.
(Adapted from multiple sources, including reference 4.)

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Techniques in Regional Anesthesia and Pain Management, Vol 13, No 2, April 2009
cellular processes that regulate the synthesis and turnover of
extracellular components, such as collagen and proteoglycans.

Vascular and nervous supply

Figure 4 Posterior oblique view diagram of the intervertebral

disc and vertebrae with the posterior elements removed. 1, intervertebral disc; 2, posterior longitudinal ligament; 3, spinal nerve
root; 4, vertebral body; 5, segmental artery; 6, interosseous arteries; 7, dorsal root ganglion with accompanying blood vessel; 8,
descending branch of the sino-vertebral nerve; 9, ascending branch
of the sino-vertebral nerve; 10, aorta. (Adapted from multiple
sources, including reference 4.)

disc with tensile strength. The matrix of the nucleus pulposus and the endplate are formed of collagen II (synthesized
by chondrocyte-like cells), proteoglycans, and noncollagenous proteins. Type I and type II collagen fibrils for the
annulus fibrosus are produced by fibroblast-like cells. Proteoglycans are aggregated together by hyaluronic acid and
further by collagen II and collagen IX.13
Aggrecan, containing highly anionic glycosaminoglycans, is the major proteoglycan of the disc. Its components,
chondroitin and keratin sulfate, retain water due to their
osmotic pressure and hence maintain tissue hydration. The
nucleus has a higher concentration of proteoglycans (and
consequently a higher degree of hydration) than the annulus.
Although aggrecan in the articular cartilage contains some
keratin sulfate, the disc aggrecan has far more. In addition,
the disc aggrecan has a higher degree of variability in its
composition, with many smaller, more degraded and less
aggregated molecules.
The matrix is dynamic and constantly in a state of flux.
Its constituents are continually being broken down by proteinases, such as the matrix metalloproteinase (MMP) and
aggrecanases synthesized by disc cells. The discs mechanical properties are determined by the quality and integrity of
the matrix. Homeostasis is maintained within the disc by

Branches of the spinal artery are present in the cartilaginous

endplates before the first year of life, but are later present
only in the longitudinal ligaments to either side of the disc
and occasionally in the outermost portions (outer 3.5 mm)
of the annulus. Branches from the segmental artery provide
blood supply to the vertebral body and the endplate of the
disc. Nerves accompanying the vessels originate near the
disc space and are branches of the recurrent sino-vertebral
nerve (Figure 4). The nerve enters the foramen at a particular level after branching off from the dorsal root ganglion.
Once in the foramen, it divides into a more prominent
ascending and a less prominent descending branch. The
gray rami communicantes from dorsal root ganglia also has
a significant contribution to the nerve supply (Figure 5). The
fact that sensory information from the sino-vertebral nerve
may reach the spinal cord segmentally through the dorsal
horn or extrasegmentally through the paravertebral sympathetic chain may explain the diffuse spatial nature of pain
besides the overlap from adjacent sino-vertebral nerves into
three segments. Mechanoreceptors and free nerve endings
have been found in the annulus. The dorsal root ganglion
also provides branches that allow afferent innervation to the
anterior longitudinal ligament. The posterior longitudinal
ligament and the outer annulus fibrosus layers contain
plenty of nociceptive fibers that originate from the ascend-

Figure 5 Innervation of the intervertebral disc. 1, intervertebral

disc; 2, recurrent sino-vertebral nerve; 3, spinal nerve; 4, posterior
branch of spinal nerve; 5, thecal sac with spinal roots; 6, paraspinal
muscle. (Adapted from multiple sources, including reference 4.)

Shankar et al

Anatomy and Pathophysiology of Intervertebral Disc

ing branch of the sino-vertebral nerve. Schwann cells also

appear to accompany the nerves in discs and play some role
in neural and vascular proliferation in an injured disc. By
the second or third decade, the healthy adult disc has some
innervation restricted to the outer annulus to about 3 mm
that may provide a source for pain perception, but it normally has very little vasculature unless there has been some
degree of degeneration.14 In the young adult, the cartilaginous endplate, like other areas of the body that are composed of hyaline cartilage, contains no blood vessels or
nerves.6

Nutrient exchange
A consistent supply of essential nutrients and oxygen as
well as a means for removal of metabolic end products such
as lactate is required to support the aerobic metabolism
needed to synthesize collagen and proteoglycans, thus enabling optimal cellular function. Most of the discs blood
supply is usually limited to the outer annulus. Given this
fact, the nearest source of blood to the overwhelming majority of adult disc tissues is located in the subchondral
regions of the vertebral bodies. With this tenuous blood
supply, the disc depends solely upon bulk fluid flow for the
transport of large molecules and diffusion for the transport
of small molecules into and out of the disc. These molecules
may traverse a substantial distance, perhaps as far as 20 mm
from the blood source to the center of the disc. The molecules transported must extravasate from the capillaries into
the subchondral bone, cross the vertebral endplate, and then
travel through the extracellular matrix of the disc to center.
This journey must then be traversed in reverse for the
removal of metabolic waste. Rajasakaran and coworkers
tracked diffusion with a gadolinium-enhanced lumbar MRI.
They found that molecules took 2 hours to cross the endplate from the vertebral body and 4 hours to accumulate to
any significant degree in the center of the disc.15 When one
considers the number of different tissues traversed as well
as the sheer distance, it is amazing that any exchange of
nutrients and wastes in the disc takes place via diffusion or
bulk flow.
Electrochemical events as well as mechanical barriers
dictate the velocity of the discs tissuefluid exchange.16
Mechanical barriers would include fibrous tissues near
and within the disc as well as the vertebral endplates. The
potent negative charges exerted by proteoglycans to attract and bind water is a type of electrochemical force.
Proteoglycan-induced increased binding of water improves the compressive strength of the nucleus. Spinal
loading and unloading may influence proteoglycan activity in the disc, which may in turn account for the large
degree of variation in the nucleuss compressive strength
from 630 to 2900 lbs.17

71

Physiological changes
When the nuclear region of the young, healthy disc is
analyzed with a T2-weighted magnetic resonance (MR)
imaging, a diurnal variation becomes apparent. The signal
intensity, which correlates with a higher concentration of
water, is elevated in the morning hours after lying down for
several hours overnight and is lower in the evening (correlating with less hydration) after several hours of standing or
sitting in the upright position. This indicates that loading
and unloading the spine appears to create gradients that
influence the degree of tissuefluid exchange. A 19.3-mm
average increase in total body height and an average disc
volume increase of 1300 mm3 in young, healthy females
after lying recumbent for several hours was reported.18
Similarly a 0.9-mm loss in the height of a disc during the
span of a day in healthy adults was documented.19 Yet
another study reported that degenerative discs and nondegenerated discs in subjects over 35 years of age did not
exhibit appreciable diurnal variations.20 The absence of
significant diurnal variations in older and degenerated discs
supports the findings of Rajasekaran and coworkers, who
conclude that any degree of inability to perform fluid exchange is a key element of degenerative disc disease.15

Pressure transmission
As previously discussed, the hydraulic mechanism needed to
both transmit and absorb forces through the disc is primarily
dependent on the degree to which the nucleus is hydrated as
well as the structural integrity of the annulus and the vertebral
endplate. The primary function of the nucleus is to decrease
stress on the vertebral endplate. The vertebral endplate and
annulus both contain and restrain the force of the nucleus.
Normally, functioning discs disperse forces evenly. However,
any compromise of the functional integrity of the nucleus, the
annulus, or the endplate can alter the balance of forces and
decrease disc function.

Age-related histologic changes

Each of the structures comprising the intervertebral disc undergoes histologic changes with aging. The annulus, which is
composed of fibrous connective tissue, in infancy gets increasingly hyalinized with collagen fibers, and at the third
decade of life starts showing fissures. Later by the fourth
decade, mismatch of cell death and cellular proliferation
develops, leading to invasion of vasculature through the
clefts and tears. The nucleus shows gradual replacement of
the notochordal cells with chondrocytes in the second decade. Subsequent decades show the occurrence of clefts,
which lead to the formation of fibrous tissue later in life.
The endplate has vasculature up to the third decade. It gets
thinned with formation of clefts and fissures in the fourth

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decade and finally is replaced by fibrocartilage in the sixth

decade.21 There is also a temporal relationship between the
changes in various disc components. The endplates show
the earliest changes followed by the nucleus and then the
annulus. The decrease in endplate vasculature in the teens
may be the critical factor leading to loss of nutrients and
oxygen for the nucleus, leading to further degeneration.22
Increased crosslinks due to reaction between collagen and
glucose give the older discs a yellow color. Matrix synthesis
also decreases with aging.

Causes of disc degeneration

Disc degeneration includes real or apparent desiccation,
fibrosis, narrowing of the disc space, diffuse bulging of the
annulus beyond the disc space, extensive fissuring (ie, numerous annular tears) and mucinous degeneration of the
annulus, defects and sclerosis of the endplates, and osteophytes at the vertebral apophyses.23 Although the list of
contributing factors to disc degeneration has not changed
over the last several years, the degree of importance attributed to each factor has significantly changed over the last
decade. Higher associations with disc degenerations were
found with body weight, lifting strength, and axial disc area
than physical activity.24 Occupational risks, such as exposure to vibrations, heavy manual labor (and concomitant
forces in the lumbar spine) leading to endplate damage, and
smoking and atherosclerosis causing decrease in nutrient
supply, are all traditionally believed to play a role in disc
degeneration. The role of genetic predisposition to disc
degeneration as the primary risk factor is being increasingly
recognized.25 More specifically, there appears to be some
genetic variation in the rate, degree of synthesis, and breakdown in the primary structural components of the disc, such
as the collagen.26 Collagen IX encoding genes (COL9A2,
COL9A3) are the most studied showing substitution of
tryptophan. Similarly, candidate genes encoding for type I
collagen (COL1A 1-Sp1 binding site), Sox 9, which regulates other genes like the gene encoding aggrecan, vitamin
D receptor gene, matrix metalloproteinase-3 gene, responsible for degeneration and interleukin-1 polymorphisms are
being studied for possible association with disc degeneration.27 High prevalence of disc degeneration was noted in
knockout mice for aggrecan.28 In addition, there appears to
be some genetic variation in the size and shape of many
structural components of the spine.
The Twin Spine study, which included both monozygotic
and dizygotic twins from the Finnish Twin cohort registry,
revealed that there was little effect on physical loading to
the contribution of disc degeneration. They failed to find a
smoking-related effect. Interestingly by multivariate analysis comparing the spine MRIs from 115 monozygotic twins,
they found that including age and work with familial aggregation improved the explanation for the variability to
74%.29 The disc degeneration as seen in MRIs had a striking

similarity among the twins.30,31 Patients who were diagnosed with herniated discs before the age of 21 were four to
five times more likely to have a significant family history
for disc herniation. Patients with significant osteoarthritis of
the extremities have a greater degree of osteoarthritis and
disc degeneration of the spine. Furthermore, there may be a
genetic link between disc degeneration, degenerative scoliosis,
and spondylolisthesis through similar cellular processes.32
In addition to pathologic processes that occur over time
leading to accelerated degeneration of discs, there is also a
nonpathological degeneration that is inherent with the aging
process independent of trauma or predisposing genetic variation. Two key normal processes that occur with natural
disc degeneration are reduced proteoglycan content within
the disc (and consequent decreased hydration and function)
and decreased endplate permeability (and consequent decreased metabolic exchange). Simultaneously, the type II
collagen molecules are replaced by the denser type I collagen molecules in the nucleus. These type I molecules tend
to crosslink and form even denser tissue that further inhibits
exchange of nutrients and metabolic waste. Although these
changes lead to increased disc desiccation, and decreased
function, it is important to note that they do not substantially
decrease disc height, nor do they invoke an extremely painful response. Similar changes also occur in the articular
cartilage. These changes are easily noticed on an MRI in
which the cartilage (or the disc) takes on a darker appearance as they become less hydrated.

Pathologic features of disc degeneration

Compromise of the annulus or the vertebral endplate leads
to loss of restraint or opposing forces to the nucleus. Initially a weak small area of the annulus or endplate, perhaps
secondary to trauma, shows signs of degeneration. This
gradually spreads over time to lead to global disc degeneration and compromises the intrinsic ability of the disc to
oppose extrinsic forces. This correlates with bulging, herniation, and decreased disc height as well as associated
changes in the anterior and posterior elements of the spine
as these bony structures are called upon to provide more
support.12
One interesting finding is the difference in the rates of
diffusion of the endplates of otherwise indistinguishable
discs. Those that are symptomatic have a decreased diffusion rate as compared with those that are asymptomatic.19
Degeneration seems to be initiated with the production of
abnormal components in the matrix or increase in the factors responsible for matrix degradation (like TNF-, IL-1,
and others), and MMPs (specifically collagenase, stromelysin, gelatinase aside from MMPs 2, 7, 8, and 13) with a
reduction in tissue inhibitors. The increase in growth factors
triggers a reparative process, albeit poor.33
Circumferential tears, peripheral rim tears, and radial
fissures are the distinguishable annular tears. Although

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Anatomy and Pathophysiology of Intervertebral Disc

common at the age of 10, they peak in the middle age.

Repetitive compressive interlaminar shear stress is thought
to contribute to circumferential tears. The peripheral rim
tears are more common in the anterior portion and may be
related to trauma.17 The radial fissures project posteriorly
from the nucleus possibly following nuclear degeneration.
Radial fissures and concentric tears in the annulus seem to be
preceded by nuclear clefts.34 Following radial fissures, the
nucleus may either extrude or protrude, depending on the
percentage of dimensions of the herniated disc material.17 If
the nuclear material protrudes through the outer layer of the
annulus and into the vertebral foramen or lateral recess, it
could cause compression and subsequent edema on the
dorsal root ganglia or ignite a severe inflammatory reaction
leading to ipsilateral paraesthesias and pain.35 Application
of nuclear material to the nerve root produces inflammatory
reaction in the nerves.35 Internal disc disruption occurs
more commonly anteriorly following nuclear decompression. Although not all disc herniations are symptomatic, the
likelihood of clinical significance increases with size. The
disc prolapse, narrowing, internal disc disruption, and radial
fissures seem to be associated with pain.17

Disc repair
Following disc disruptions, the discs have a very limited
capacity to heal or to restore their structural integrity. The
outer portion of the annulus is vascularized and heals
through an inflammatory process, but the sparse population
of cells in this area does not produce sufficient quantity or
quality of collagen to replace any structural damage. Sufficiently large tears with less access to cells will in fact be
replaced with granulation tissue that lacks the tensile

Figure 6
stenosis.

Axial T2-weighted MR image of disc showing spinal

73

Figure 7 Axial T2-weighted MR image of disc showing disc

herniation.

strength of collagen. The outer annulus forms only a peripheral scar tissue after a scalpel wound. This makes one
wonder about the safety of performing decompressive or
thermo-ablative procedures on the disc. The collagen turnover time is longer than the average lifespan of humans.
Injuries to the nucleus or the endplate undergo severe degeneration of the disc following decompression.17
The complexities of disc degeneration-induced pain and
the number of variables that are involved likely accounts for
the great degree of variation between different patients and
disc injuries. With the influx of inflammatory mediators into
the annulus, there is a proliferation of blood vessels and
nerves deeper into the disc, which would allow for nociception in areas with no prior innervation.36-38 Additionally, the
influx of inflammatory mediators, such as tumor necrosis
factor, substance P, or interleukins, will lead to hyperalgesia.39,40
Following disc injury, an inflammatory cascade is initiated. This leads to build up of lactic acid, increased secretion of proteolytic enzymes, decreased proteoglycan production, decreased hydration, cell apoptosis, and further
structural breakdown of the intradiscal components. Over
time, there may be a loss of disc height, bulging of the
periphery of the disc with slackening of the supporting
fibrous tissues, and a reduction of the contribution of the
disc to axial forces. This, in turn, causes maldistribution of
forces to the surrounding structures. One to three millimeters of decrement to disc height has the potential to cause
and overload the facet joint, which could lead to facet
hypertrophy and dysfunction. The combination of a hypertrophied facet, bowed annulus, and ligamental hypertrophy
could significantly decrease the cross-sectional area of the
foramen and lead to symptomatic spinal stenosis.7

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Techniques in Regional Anesthesia and Pain Management, Vol 13, No 2, April 2009
plate trauma may also be associated with Schmorls nodes
or even bone marrow edema in nearby vertebral bodies.48
Peripheral rim lesions in the outer most annulus are
thought to be secondary to trauma. These lesions have been
suggested to correlate with high intensity zones on T2weighted MR imaging that are thought to represent associated hemorrhage or edema.

Conclusions

Figure 8 Sagittal T2-weighted MR image of lumbar spine

showing Schmorls node at the level of T11 and an extruded disc
material at the level of L5-S1. All the lumbar discs show disc
degeneration and loss of disc height. Type 1 Modics changes seen
in lumbar 1 and 2 vertebral bodies.

MR imaging of disc degeneration

MRI findings of disc degeneration include disc space narrowing, T2 weighted signal intensity loss from the intervertebral disc, presence of fissures, vacuum changes and calcification within the intervertebral disc, ligamentous signal
changes, marrow signal changes, osteophytosis, disc herniation, malalignment, and stenosis23 (Figures 6 and 7). MR
imaging currently is the major modality for investigating
disc degeneration. Vacuum phenomenon is seen with the
collection of gas in areas of negative pressure and appears
as a signal void in spin echo images. With calcification,
T1-weighted images may show hyperintense discs. Modic
described three different changes in signal intensity in the
vertebral body marrow adjacent to the endplate sometimes
referred to as Modics changes (Figure 8). Type 1 changes
appear as decreased signal intensity on T1 and increased on
T2-weighted images. This may be a form of acute degenerative change and may predict better surgical outcome.
Type 2 changes have increased signal intensity with T1 and
slightly hyperintense or no change in T2-weighted images.
Type 3 has decreased signal intensity on both T1 and T2
images and is associated with extensive sclerosis. Although
type 2 changes are supposedly more stable, type 1 and 2
may revert to the other. Although it has been theorized that
this finding could distinguish a painful versus nonpainful
degenerative disc, the evidence does not support this.41-46 A
correlation was suggested between the state of hydration of
the disc and signal intensity of the nucleus pulposus, but it
more likely reflects the status of proteoglycans.22,47 End-

Our understanding of both the natural and clinically relevant

pathologic degeneration of the spine has increased tremendously over the last several decades. To best address a
patients pain we must have a thorough understanding of the
anatomy and pathophysiology. With the invention of newer
imaging modalities, like the dynamic spine MR, ultra short
echo time imaging, and apparent diffusion coefficient, the
future looks more promising in terms of our ability to detect
subtle changes in the disc.23

Acknowledgments
We thank Quinn Hogan, MD, for kindly providing the
cryo-microtome pictures, John Joseph, MD, for providing
the MR images, and DeWayne Risley for doing the color
illustrations.

References
1. Boos N, Weissbach S, Rohrbach H, et al: Classification of age-related
changes in lumbar intervertebral discs: 2002 Volvo award in basic
science. Spine 27:2631-2644, 2002
2. Miller JA, Schmatz C, Schultz AB: Lumbar disc degeneration: Correlation with age, sex, and spine level in 600 autopsy specimens. Spine
13:173-178, 1988
3. Luoma K, Riihimaki H, Luukkonen R, et al: Low back pain in relation
to lumbar disc degeneration. Spine 25:487-492, 2000
4. Raj PP: Intervertebral disc: Anatomy-physiology-pathophysiologytreatment. Pain Pract 8:18-44, 2008
5. Maniadakis N, Gray A: The economic burden of back pain in the UK.
Pain 84:95-103, 2000
6. Coventry MB, Ghormley RK, Kernohan JW: The intervertebral disc:
Its microscopic anatomy and pathology. Part I. Anatomy, development, and physiology. J Bone Joint Surg Am 27:105-112, 1945
7. Pye SR, Reid DM, Lunt M, et al: Lumbar disc degeneration: Association between osteophytes, end-plate sclerosis and disc space narrowing. Ann Rheum Dis 66:330-333, 2007
8. Weishaupt D, Zanetti M, Hodler J, et al: Painful lumbar disk derangement: Relevance of endplate abnormalities at MR imaging. Radiology
218:420-427, 2001
9. Edgar MA: The nerve supply of the lumbar intervertebral disc. J Bone
Joint Surg Br 89:1135-1139, 2007
10. Fagan A, Moore R, Vernon Roberts B, et al: The innervation of the
intervertebral disc: A quantitative analysis. Spine 28:2570-2576, 2003
11. Errington RJ, Puustjarvi K, White IR, et al: Characterization of cytoplasm-filled processes in cells of the intervertebral disc. J Anat 192:
369-378, 1998

Shankar et al

Anatomy and Pathophysiology of Intervertebral Disc

12. Singh K, Masuda K, Thonar EJ, et al: Age-related changes in the

extracellular matrix of nucleus pulposus and anulus fibrosus of human
intervertebral disc. Spine 34:10-16, 2009
13. Eyre DR, Matsui Y, Wu JJ: Collagen polymorphisms of the intervertebral disc. Biochem Soc Trans 30:844-848, 2002
14. Johnson WE, Evans H, Menage J, et al: Immunohistochemical detection of Schwann cells in innervated and vascularized human intervertebral discs. Spine 26:2550-2557, 2001
15. Rajasekaran S, Babu JN, Arun R, et al: ISSLS prize winner: A study
of diffusion in human lumbar discs: A serial magnetic resonance
imaging study documenting the influence of the endplate on diffusion
in normal and degenerate discs. Spine 29:2654-2667, 2004
16. Kealey SM, Aho T, Delong D, et al: Assessment of apparent diffusion
coefficient in normal and degenerated intervertebral lumbar disks:
Initial experience. Radiology 235:569-574, 2005
17. Adams MA, Roughley PJ: What is intervertebral disc degeneration,
and what causes it? Spine 31:2151-2161, 2006
18. Boos N, Wallin A, Aebi M, et al: A new magnetic resonance imaging
analysis method for the measurement of disc height variations. Spine
21:563-570, 1996
19. Roberts N, Hogg D, Whitehouse GH, et al: Quantitative analysis of
diurnal variation in volume and water content of lumbar intervertebral
discs. Clin Anat 11:1-8, 1998
20. Karakida O, Ueda H, Ueda M, et al: Diurnal T2 value changes in the
lumbar intervertebral discs. Clin Radiol 58:389-392, 2003
21. Coventry MB, Ghormley RK, Kernohan JW: The intervertebral disc:
Its microscopic anatomy and pathology. Part II. changes in the intervertebral disc concomitant with age. J Bone Joint Surg Am 27:233237, 1945
22. Horner HA, Urban JP: Volvo award winner in basic science studies:
Effect of nutrient supply on the viability of cells from the nucleus
pulposus of the intervertebral disc. Spine 26:2543-2549, 2001
23. Modic MT, Ross JS: Lumbar degenerative disk disease. Radiology
245:43-61, 2007
24. Videman T, Levalahti E, Battie MC: The effects of anthropometrics,
lifting strength, and physical activities in disc degeneration. Spine
32:1406-1413, 2007
25. Battie MC, Videman T: Lumbar disc degeneration: Epidemiology and
genetics. J Bone Joint Surg Am 88:3-9, 2006 (suppl 2)
26. Battie MC, Videman T, Parent E: Lumbar disc degeneration: Epidemiology and genetic influences. Spine 29:2679-2690, 2004
27. Zhang Y, Sun Z, Liu J, et al: Advances in susceptibility genetics of
intervertebral degenerative disc disease. Int J Biol Sci 4:283-290, 2008
28. Watanabe H, Nakata K, Kimata K, et al: Dwarfism and age-associated
spinal degeneration of heterozygote cmd mice defective in aggrecan.
Proc Natl Acad Sci U S A 94:6943-6947, 1997
29. Videman T, Battie MC, Gibbons LE, et al: Associations between back
pain history and lumbar MRI findings. Spine 28:582-588, 2003
30. Battie MC, Haynor DR, Fisher LD, et al: Similarities in degenerative
findings on magnetic resonance images of the lumbar spines of identical twins. J Bone Joint Surg Am 77:1662-1670, 1995
31. Batti MC, Videman T, Kaprio J, et al: The twin spine study: Contributions to a changing view of disc degeneration. Spine J 9:47-59, 2009

75

32. Johnson WE, Roberts S: Human intervertebral disc cell morphology

and cytoskeletal composition: A preliminary study of regional variations in health and disease. J Anat 203:605-612, 2003
33. Hadjipavlou AG, Tzermiadianos MN, Bogduk N, et al: The pathophysiology of disc degeneration: A critical review. J Bone Joint Surg
Br 90:1261-1270, 2008
34. Haefeli M, Kalberer F, Saegesser D, et al: The course of macroscopic
degeneration in the human lumbar intervertebral disc. Spine 31:15221531, 2006
35. Olmarker K, Rydevik B, Nordborg C: Autologous nucleus pulposus
induces neurophysiologic and histologic changes in porcine cauda
equina nerve roots. Spine 18:1425-1432, 1993
36. Zhao JG, Jia CQ, Zhang P: The possible process of neovascularization
in degeneration intervertebral disc. Med Hypotheses 72:361-362, 2009
37. Abe Y, Akeda K, An HS, et al: Proinflammatory cytokines stimulate
the expression of nerve growth factor by human intervertebral disc
cells. Spine 32:635-642, 2007
38. Aoki Y, Ohtori S, Takahashi K, et al: Innervation of the lumbar
intervertebral disc by nerve growth factor-dependent neurons related to
inflammatory pain. Spine 29:1077-1081, 2004
39. Weiler C, Nerlich AG, Bachmeier BE, et al: Expression and distribution of tumor necrosis factor alpha in human lumbar intervertebral
discs: A study in surgical specimen and autopsy controls. Spine 30:
44-53, discussion 54, 2005
40. Brisby H: Pathology and possible mechanisms of nervous system
response to disc degeneration. J Bone Joint Surg Am 88:68-71, 2006
(suppl 2)
41. Modic MT: Modic type 1 and type 2 changes. J Neurosurg Spine
6:150-151, 2007
42. Carragee E, Alamin T, Cheng I, et al: Are first-time episodes of serious
LBP associated with new MRI findings? Spine J 6:624-635, 2006
43. Carragee EJ, Alamin TF, Miller JL, et al: Discographic, MRI and
psychosocial determinants of low back pain disability and remission:
A prospective study in subjects with benign persistent back pain. Spine
J 5:24-35, 2005
44. Kjaer P, Leboeuf-Yde C, Korsholm L, et al: Magnetic resonance
imaging and low back pain in adults: A diagnostic imaging study of
40-year-old men and women. Spine 30:1173-1180, 2005
45. Kleinstuck F, Dvorak J, Mannion AF: Are structural abnormalities
on magnetic resonance imaging a contraindication to the successful
conservative treatment of chronic nonspecific low back pain? Spine
31:2250-2257, 2006
46. Mitra D, Cassar-Pullicino VN, McCall IW: Longitudinal study of
vertebral type-1 end-plate changes on MR of the lumbar spine. Eur
Radiol 14:1574-1581, 2004
47. Tertti M, Paajanen H, Laato M, et al: Disc degeneration in magnetic
resonance imaging. A comparative biochemical, histologic, and radiologic study in cadaver spines. Spine 16:629-634, 1991
48. Modic MT, Steinberg PM, Ross JS, et al: Degenerative disk disease:
Assessment of changes in vertebral body marrow with MR imaging.
Radiology 166:193-199, 1988