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Intervertebral Disc: Anatomy-Physiology-

Pathophysiology-Treatment

Article in Pain Practice April 2008

DOI: 10.1111/j.1533-2500.2007.00171.x Source: PubMed

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 REVIEW ARTICLE

Intervertebral Disc:
Anatomy-Physiology-
Pathophysiology-Treatment

P. Prithvi Raj, MD, FIPP, ABIPP

Department of Anesthesiology and Pain Management, Texas Tech University, Lubbock,
Texas, U.S.A.

Abstract: This review article describes anatomy, physiol- Back pain is a major public health problem in Western
ogy, pathophysiology and treatment of intervertebral disc. industrialized societies. The prevalence rates in a
The intervertebral discs lie between the vertebral bodies, number of studies ranged from 12% to 35%,1 with
linking them together. The components of the disc are
around 10% of patients becoming chronically disabled.
nucleus pulposus, annulus fibrosus and cartilagenous end-
plates. The blood supply to the disc is only to the cartilag-
It also places an enormous economic burden on
enous end-plates. The nerve supply is basically through the society.
sinovertebral nerve. Biochemically, the important constitu- Back pain is strongly associated with degeneration of
ents of the disc are collagen fibers, elastin fibers and aggre- the intervertebral disc.2 Disc degeneration, although in
can. As the disc ages, degeneration occurs, osmotic pressure many cases asymptomatic,3 is also associated with sci-
is lost in the nucleus, dehydration occurs, and the disc loses its atica and disc herniation or prolapse. It alters disc height
height. During these changes, nociceptive nuclear material
and the mechanics of the rest of the spinal column,
tracks and leaks through the outer rim of the annulus. This is
possibly adversely affecting the behavior of other spinal
the main source of discogenic pain. While this is occurring,
the degenerative disc, having lost its height, effects the struc- structures such as muscles and ligaments. In the long
tures close by, such as ligamentum flavum, facet joints, and term, it can lead to spinal stenosis, a major cause of pain
the shape of the neural foramina. This is the main cause of and disability in the elderly; its incidence is rising expo-
spinal stenosis and radicular pain due to the disc degenera- nentially with current demographic changes and an
tion in the aged populations. increased aged population.
Diagnosis is done by a strict protocol and treatment Discs degenerate far earlier than do other musculosk-
options are described in this review. The rationale for new
eletal tissues; the first unequivocal findings of degenera-
therapies are to substitute the biochemical constituents, or
augment nucleus pulposus or regenerate cartilaginous end-
tion in the lumbar discs are seen in the age group 11 to
plate or finally artificial disc implantation. . 16 years.4 About 20% of people in their teens have discs
with mild signs of degeneration; degeneration increases
Key Words: Intervertebral disc, disc disease, Annu- steeply with age, particularly in males, so that around
loplasty, disc decompression 10% of 50-year-old discs and 60% of 70-year-old discs
are severely degenerate.5
Address correspondence and reprint requests to: P. Prithvi Raj, MD,
FIPP, ABIPP, 1097 Cameron Glen, Cincinnati, OH 45245, U.S.A. E-mail:
prithviraj@fuse.net. ANATOMY
Submitted: August 18, 2007; Revision accepted: October 23, 2007
The Normal Disc
2008 World Institute of Pain, 1530-7085/08/$15.00
The intervertebral discs lie between the vertebral bodies,
Pain Practice, Volume 8, Issue 1, 2008 1844 linking them together (Figure 1). They are the main
 Intervertebral Disc 19

Figure 1. A line drawing of the spinal segment consisting of two

vertebral bodies and a normal intervertebral disc sandwiched
between them.

Figure 3. The central Nucleus Pulposus containing collagen

fibers and elastin fibers. The solidified portion of the Nucleus
Pulposus is surrounded by gel-like Nucleus Pulposus.

surrounds a more gelatinous core known as the nucleus

pulposus; the nucleus pulposus is sandwiched inferiorly
and superiorly by cartilage endplates.

Structure of the Nucleus Pulposus

The central nucleus pulposus contains collagen fibers,
which are organized randomly,8 and elastin fibers
(sometimes up to 150 mm in length), which are arranged
Figure 2. A cut out portion of a normal disc. Note the location of
the Nucleus Pulposus, the vertebral end plate and the architec- radially;9 these fibers are embedded in a highly
ture of Annulus Fibrosis. The intervertebral disc is 4 cm wide and hydrated aggrecan-containing gel (Figure 3). Inter-
710 mm thick. spersed at a low density (approximately 5000/mm3,10 are
chondrocyte-like cells, sometimes sitting in a capsule
within the matrix. Outside the nucleus is the annulus
joints of the spinal column and occupy one-third of fibrosus, with the boundary between the two regions
its height. Their major role is mechanical, as they con- being very distinct in the young individual (<10 years).
stantly transmit loads arising from body weight and
muscle activity through the spinal column. They provide Structure of the Annulus
flexibility to this, allowing bending, flexion, and torsion. This is made up of a series of 15 to 25 concentric rings,
They are approximately 7 to 10 mm thick and 4 cm in or lamellae,11 with the collagen fibers lying parallel
diameter (Figure 2) (anteriorposterior plane) in the within each lamella. The fibers are oriented at approxi-
lumbar region of the spine.6,7 The intervertebral discs mately 60 to the vertical axis, alternating to the left and
are complex structures that consist of a thick outer ring right of it in adjacent lamellae. Elastin fibers lie between
of fibrous cartilage termed the annulus fibrosus, which the lamellae, possibly helping the disc to return to its
20 raj

Figure 4. The organization of the vertebral endplate containing

hyaline cartilage bonded to the perforated cortical bone of the
vertebral body and collagen fibers of the annulus and the
nucleus. Arrows indicate routes for nutrient transport from
blood vessels into the central portion of the disc (Adapted from
J Orthop Res. 1993;11:747757).

original arrangement following bending, whether it is

flexion or extension. They may also bind the lamellae
together as elastin fibers pass radially from one lamella
to the next.9 The cells of the annulus, particularly in the
outer region, tend to be fibroblast-like, elongated, thin,
and aligned parallel to the collagen fibers. Toward the
inner annulus the cells can be more oval. Cells of the
disc, both in the annulus and nucleus, can have several
long, thin cytoplasmic projections, which may be more
than 30 mm long.12,13 Such features are not seen in
cells of articular cartilage.12 Their function in disc is
unknown but it has been suggested that they may act as
sensors and communicators of mechanical strain within
the tissue.12 Figure 5. (A) An axial section of the intervertebral disc in a
10-month-old girl. Note the numerous vascular channels and
The Structure of the Endplate wide cartilaginous endplates traversing to the annulus fibrosis
and Nucleus Pulposus. The disc is more gel-like and highly
The third morphologically distinct region is the cartilage
hydrated. (B) An axial section of the intervertebral disc of a
endplate, a thin horizontal layer, usually less than 1 mm 50-year-old adult. Note the thin cartilaginous plate and lesser
thick, of hyaline cartilage (Figure 4). This interfaces the vascular channels traversing to less hydrated distinct Annulus
disc and the vertebral body. The collagen fibers within it Fibrosis and Nucleus Pulposus.

run horizontal and parallel to the vertebral bodies, with

the fibers continuing into the disc.7 The appearance of the lae (Figure 6), some of which terminate in proprio-
intervertebral disc at young (10 months old) and adult ceptor.14 The cartilaginous endplate, like other hyaline
periods are shown in Figure 5A and B, respectively. cartilages, is normally totally avascular and aneural in
the healthy adult. Blood vessels present in the longitu-
Blood Vessels and Nerve Supply of the Disc dinal ligaments adjacent to the disc and in young carti-
The healthy adult disc has few (if any) blood vessels, but lage endplates (less than about 12 months old) are
it has some nerves, mainly restricted to the outer lamel- branches of the spinal artery.15
 Intervertebral Disc 21

Figure 6. The organization of the blood vessels branching

from the segmental artery entering the vertebral body and
Figure 7. Innervation of the PLL and the disc annulus by the
end as capillaries in the endplate (adapted from http://www.
ascending branch of the Sino-vertebral nerve.
Medscape.com).

PATHOPHYSIOLOGY
Nerves in the disc have been demonstrated, often Changes in the Disc due to Aging
accompanying these vessels, but they can also occur During growth and skeletal maturation, the boundary
independently, being branches of the sinuvertebral nerve between annulus and nucleus becomes less obvious,
or derived from the ventral rami or gray rami com- and with increasing age the nucleus generally becomes
municantes. A meningeal branch of the spinal nerve, more fibrotic and less gel-like.17 With increasing age and
known as the recurrent sinovertebral nerve, originates degeneration, the disc changes in morphology, becom-
near the disc space (Figure 7). This nerve exits from ing more and more disorganized. Often the annular
the dorsal root ganglion and enters the foramen, when lamellae become irregular, bifurcating, and interdigitat-
it then divides into a major ascending and a lesser ing and the collagen and elastin networks also appear to
descending branch. It has been shown in animal studies become more disorganized. There is frequently cleft
that further afferent contributions to the sinovertebral formation with fissures forming within the disc, par-
nerve arises via the rami communicantes from multiple ticularly in the nucleus. Nerves and blood vessels are
superior and inferior dorsal root ganglia (Figure 8). In increasingly found with degeneration.14 Cell prolifera-
addition, the anterior longitudinal ligament also receives tion occurs, leading to cluster formation (Figure 9), par-
afferent Innervation from branches that originate in the ticularly in the nucleus.18,19 Cell death also occurs, with
dorsal root ganglion. The posterior longitudinal liga- the presence of cells with necrotic and apoptotic appear-
ment (PLL) is richly innervated by nociceptive fibers ance.20,21 It has been reported that more than 50% of
from the ascending branch of the sinovertebral nerve. cells in adult discs are necrotic.20 With discs from indi-
These nerves also innervate the adjacent outer layers of viduals as young as 2 years of age having some very mild
the annulus fibrosis. Some of the nerves in discs also cleft formation and granular changes to the nucleus.
have glial support cells, or Schwann cells, alongside With increasing age comes an increased incidence of
them.16 degenerative changes, including cell death, cell prolif-
22 raj

PHYSIOLOGY
Biochemistry of the Normal Disc
The mechanical functions of the disc are served by the
extracellular matrix; its composition and organization
govern the discs mechanical responses. The main
mechanical role is provided by the two major macro-
molecular components.

Collagen Fibers
The collagen network, formed mostly of type I and
type II collagen fibrils and making up approximately
70% and 20% of the dry weight of the annulus
and nucleus, respectively,22 provides tensile strength
to the disc and anchors the tissue to the bone
(Figure 10A).

Aggrecan
Aggrecan, the major proteoglycan of the disc,23 is
Figure 8. The course of the recurrent Sino-vertebral nerve, which responsible for maintaining tissue hydration through the
innervates the Postero-lateral region of the disc. The nerve exits osmotic pressure provided by its constituent chondroitin
from the dorsal root ganglion and enters the vertebral foramen,
and keratan sulfate chains.24 The proteoglycan and
where it divides into a major ascending and a lesser descending
branch. The posterior longitudinal ligament is richly innervated water content of the nucleus (around 15% and 80%
by nociceptive fibers from the ascending branch of the of the wet weight, respectively) is greater than in the
Sino-vertebral nerve. annulus (approximately 5% and 70% of the wet weight,
respectively) (Figure 10B).

Matrix
The matrix is a dynamic structure. Its molecules are
continually being broken down by proteiniases, such
as the matrix metalloproteinase (MMPs) and aggreca-
nases, which are also synthesized by disc cells.2527 The
balance between synthesis, breakdown, and accumula-
tion of matrix macromolecules determines the quality
and integrity of the matrix, and thus the mechanical
behavior of the disc itself. The integrity of the matrix is
also important for maintaining the relatively avascular
and aneural nature of the healthy disc.
The intervertebral disc is often likened to articular
cartilage. However, there are significant differences
between the two tissues, one of these being the compo-
Figure 9. A nerve bundle in human intervertebral disc stained sition and structure of aggrecan. Disc aggrecan is more
with an antibody to neurofilament (with permission from:
Roberts S, Evans H, Menage J et al. Eur Spine J. 2005;14:3642). highly substituted with keratan sulfate than that found
in the deep zone of articular cartilage. In addition, the
aggrecan molecules are less aggregated (30%) and more
heterogeneous, with smaller, more degraded fragments
eration, mucous degeneration, granular change, and in the disc than in articular cartilage (80% aggregated)
concentric tears. It is difficult to differentiate changes from the same individual.28 Disc proteoglycans become
that occur solely due to aging from those that might be increasingly difficult to extract from the matrix with
pathological. increasing age.23
 Intervertebral Disc 23

Figure 11. (A) The proteoglycan aggregates are depicted as the

central hyaluronan molecule (dashed line) substituted with
aggrecan molecules possessing a central core protein (open line)
and sulfated glycosaminoglycan side chains (solid lines) The
hydration properties of the glycosaminoglycan chains of aggre-
can cause the tissue to swell until an equilibrium is reached,
where the swelling potential is balanced by tensile forces in the
Figure 10. (A) A line drawing of the intervertebral disc structure. collagen network. (B) Degradation of proteoglycan with the
(B) A line drawing of a disc proteoglycan aggregate. degeneration of the intervertebral disc. This results in loss of
water pressure and disc dehydration.

PATHOPHYSIOLOGY
B).29 The aggrecan molecules become degraded, with
Loss of Proteoglycan smaller fragments being able to leach from the tissue
The most significant biochemical change to occur in disc more readily than larger portions. This results in loss of
degeneration is loss of proteoglycan (Figure 11A and glycosaminoglycans; this loss is responsible for a fall in
24 raj

the osmotic pressure of the disc matrix and therefore a an optimal pH that is approximately neutral. All of
loss of hydration. these enzymes have been identified in disc.
Even in degenerate discs, however, the disc cells can
retain the ability to synthesize large aggrecan molecules Functional Changes of the Disc due to Degeneration
with intact hyaluronan-binding regions, which have the The loss of proteoglycan in degenerate discs29 has a
potential to form aggregates.23 Less is known of how the major effect on the discs load-bearing behavior. With
small proteoglycan population changes with disc degen- loss of proteoglycan, the osmotic pressure of the disc
eration, although there is some evidence that the falls35 and the disc is less able to maintain hydration
amount of decorin, and more particularly biglycan, is under load; degenerate discs have a lower water content
elevated in degenerate human discs as compared with than do normal age-matched discs,29 and when loaded
normal ones.30 they lose height36 and fluid more rapidly: the discs tend
to bulge. Loss of proteoglycan and matrix disorganiza-
Loss of Collagen Fibers tion has other important mechanical effects; because
Although the collagen population of the disc also of the subsequent loss of hydration, degenerated discs
changes with degeneration of the matrix, the changes no longer behave hydrostatically under load.37 Loading
are not as obvious as those of the proteoglycans. The may thus lead to inappropriate stress concentrations
absolute quantity of collagen changes little but the types along the endplate or in the annulus; the stress con-
and distribution of collagens can be altered. For centrations seen in degenerate discs have also been
example, there may be a shift in proportions of types of associated with discogenic pain produced during
collagens found and in their apparent distribution discography.38
within the matrix. In addition, the fibrillar collagens, Such major changes in disc behavior have a strong
such as type II collagen, become more denatured, appar- influence on other spinal structures, and may affect their
ently because of enzymic activity; the amount of dena- function and predispose them to injury. For instance, as
tured type II collagen increases with degeneration.31,32 a result of the rapid loss of disc height under load in
However, collagen cross-link studies indicate that, as degenerate discs, apophyseal joints adjacent to such disk
with proteoglycans, new collagen molecules may be syn- may be subject to abnormal loads39 and eventually
thesized, at least early in disc degeneration, possibly in develop osteoarthritic changes. Loss of disc height can
an attempt at repair.33 also affect other structures. It reduces the tensional
forces on the ligamentum flavum and hence may cause
Increase in Fibronectin remodeling and thickening. With consequent loss of
Other components can change in disc degeneration and elasticity,40 the ligament will tend to bulge into the
disease in either quantity or distribution. For example, spinal canal, leading to spinal stenosisan increasing
fibronectin content increases with increasing degenera- problem as the population ages.
tion and it becomes more fragmented.34 These elevated Loss of proteoglycans also influences the movement
levels of fibronectin could reflect the response of the cell of molecules into and out of the disc. Aggrecan, because
to an altered environment. Whatever the cause, the for- of its high concentration and charge in the normal disc,
mation of fibronectin fragments can then feed into the prevents movement of large uncharged molecules such
degenerative cascade because they have been shown to as serum proteins and cytokines into and through the
down-regulate aggrecan synthesis but to up-regulate the matrix.41 The fall in concentration of aggrecan in degen-
production of some MMPs in in vitro systems. eration could thus facilitate loss of small, but osmoti-
cally active, aggrecan fragments from the disc, possibly
Enzymatic Activity accelerating a degenerative cascade. In addition, loss of
The biochemistry of disc degeneration indicates that aggrecan would allow increased penetration of large
enzymatic activity contributes to this disorder, with molecules such as growth factor complexes and cytok-
increased fragmentation of the collagen, proteoglycan, ines into the disc, affecting cellular behavior and possi-
and fibronectin populations. Several families of enzymes bly the progression of degeneration. The increased
are capable of breaking down the various matrix mol- vascular and neural ingrowth seen in degenerate discs
ecules of disc, including cathepsins, MMPs, and aggre- and associated with chronic back pain42 is also probably
canases. Cathepsins have maximal activity in acid associated with proteoglycan loss because disc aggrecan
conditions. In contrast, MMPs and aggrecanases have has been shown to inhibit neural ingrowth.43,44
 Intervertebral Disc 25

It is now clear that herniation-induced pressure on in disc degeneration. Long-term exercise or lack of it
the nerve root cannot alone be the cause of pain because appears to have an effect on movement of nutrients
more than 70% of normal, asymptomatic people into the disc, and thus on their concentration in the
have disc prolapses pressurizing the nerve roots but no tissue.59,60
pain.3,45 A past and current hypothesis is that, in symp- The mechanism is not known but it has been sug-
tomatic individuals, the nerves are somehow sensitized gested that exercise affects the architecture of the capil-
to the pressure,46 possibly by molecules arising from an lary bed at the discbone interface. Finally, even if the
inflammatory cascade from arachidonic acid through blood supply remains undisturbed, nutrients may not
to prostaglandin E2, thromboxane, phospholipase A2, reach the disc cells if the cartilaginous endplate calci-
tumor necrosis factor-a,47 the interleukins, and MMPs. fies;50,61 intense calcification of the endplate is seen in
These molecules can be produced by cells of herniated scoliotic discs.
discs and because of the close physical contact between
the nerve root and disc following herniation they may be
able to sensitize the nerve root.48,49 The exact sequence Effect of Mechanical Load and Injury to the Disc
of events and specific molecules that are involved have Abnormal mechanical loads are also thought to provide
not been identified. a pathway to disc degeneration. For many decades, it
was suggested that a major cause of back problems is
Nutritional Pathways of Disc Degeneration injury, often work-related, that causes structural
One of the primary causes of disc degeneration is damage. It is believed that such an injury initiates a
thought to be failure of the nutrient supply to the pathway that leads to disc degeneration and finally to
disc cells.50 Like all cell types, the cells of the disc clinical symptoms and back pain.62 Although intense
require nutrients such as glucose and oxygen to remain exercise does not appear to affect discs adversely63 and
alive and active. In vitro, the activity of disc cells is discs are reported to respond to some long-term loading
very sensitive to extracellular oxygen and pH, with regimens by increasing proteoglycan content,64 experi-
matrix synthesis rates falling steeply at acidic pH mental overloading65 or injury to the disc66,67 can induce
and at low oxygen concentrations,51,52 and the cells do degenerative changes.
not survive prolonged exposure to low pH or glucose
concentrations.53 A fall in nutrient supply that leads
to a lowering of oxygen tension or of pH (arising
from raised lactic acid concentrations) could thus
affect the ability of disc cells to synthesize and main-
tain the discs extracellular matrix and could ulti-
mately lead to disc degeneration. The disc is large and
avascular and the cells depend on blood vessels at their
margins to supply nutrients and remove metabolic
waste.54 The pathway from the blood supply to the
nucleus cells is precarious because these cells are sup-
plied virtually entirely by capillaries that originate in
the vertebral bodies, penetrating the subchondral
plate and terminating just above the cartilaginous
endplate.15,55 Nutrients must then diffuse from the
capillaries through the cartilaginous endplate and the
dense extracellular matrix of the nucleus to the cells,
which may be as far as 8 mm from the capillary bed
(Figure 12).
The nutrient supply to the nucleus cells can be dis- Figure 12. Nutritional pathways of the normal disc. The disc is
turbed at several points. Factors that affect the blood large and avascular and depends on the blood supply at the
margins to supply nutrients and remove metabolic waste. The
supply to the vertebral body such as atherosclero-
pathway from the blood supply to the nucleus cells is precarious
sis,56,57 sickle cell anemia, Caisson disease, and Gauch- because these cells are supplied virtually, entirely by capillaries
ers disease58 all appear to lead to a significant increase that originate in the vertebral bodies.
26 raj

Genetic Factors in Disc Degeneration back of the disc into the epidural space. The presence of
More recent work suggests that the factors that lead to a disc bulge and/or disc herniation is also included in this
disc degeneration may have important genetic compo- category. This condition is classified as grade 3 IDD, or
nents. Several studies have reported a strong familial grade 3 radial annular tear. This disc pathology produces
predisposition for disc degeneration and herniation.6870 the same incidence of patients having sciatica as the grade
Findings from two different twin studies conducted 2 IDD patients. This indicates the nerve fibers in the
during the past decade showed heritability exceeding posterior annulus are a strong trigger for the of annular
60%.71,72 Magnetic resonance images in identical twins tears.80 This classification has been modified by percep-
were very similar with respect to the spinal columns and tion of sciatic pain in the lower limbs.
the patterns of disc degeneration.73
CT Classification of Annular Tears
Genes associated with disc generation have been
identified. Individuals with a polymorphism in the The following classification was finalized in the 1990s
aggrecan gene were found to be at risk for early disc and is the gold standard for the computerized tomogra-
degeneration. Studies of transgenic mice have demon- phy (CT) classification of annular tears.80 This classifi-
strated that mutations in structural matrix molecules cation has been modified by Bogduk et al.81 in 1992, and
such as aggrecan,74 collagen II,75 and collagen IX76 can then further modified by Schellhas et al. in 1996.82
lead to disc degeneration. Mutations in genes other than There are five possible severities of the radial annular
those of structural matrix macromolecules have also tear as seen on an axial CT image (Figure 13).
been associated with disc degeneration.7779 The grade 0 is a normal disc, where no contrast
material injected in the center of the disc has leaked from
the confines of the nucleus pulposus. The grade 1 tear has
CLASSIFICATION OF PATHOLOGY OF leaked contrast material but only into the inner one-third
DISC DEGENERATION of the annulus. In the grade 2 tear, the contrast has leaked
The disc lesions can be classified as Contained or Her- from the nucleus into the outer two-thirds of the annulus.
niated. The progression of disc degeneration can further The grade 3 tear has leaked contrast completely through
be classified as follows: all three zones of the annulus. This tear is believed to be
Grade 0: Normal nonleaking nucleus. painful since the outer one-third of the disc has many tiny
Grade 1: Annular tearing confined to the inner region nerve fibers that are irritated. The grade 4 tear is more
of the annulus fibrosis. In grade 1, a tear or fissure serious form of the grade 3 tear, in that now the contrast
becomes visible. It extends from the nucleus radially has spread circumferentially around the disc, often
into the inner one-third of the annulus fibrosus. This is resembling a ships anchor. To qualify as a grade 4 tear,
described as a grade 1 Radial Annular Tear, or grade 1 the spread must encompass greater than 30 degrees of the
internal disc disruption (IDD). disc circumference. Pathologically, this represents the
Grade 2: In this condition, annular tears have com- merging of a full thickness radial tear with a concentric
pletely disrupted the disc architecture but do not affect annular tear. The grade 5 tear includes either a grade 3 or
the outer contour of the annulus. The entire anulus is grade 4 radial tear that has completely ruptured the outer
disrupted. There is no leakage of injected dye on discog- layers of disc and is leaking contrast material from the
raphy from the disc, nor bulging nor protrusion of the disc into the epidural space. This type of tear is thought to
disc. This state of the disc is classified as grade 2 IDD or have the ability to induce a severe inflammatory reaction
a grade 2 radial annular tear. There is no compressive in the adjacent neural structures. In some patients, this
effect on the corresponding nerve root. Many of these inflammatory process is so severe that it causes a painful
patients with (grade 2 IDD) complain of lower back chemical radiculopathy and sciatica without the presence
pain, which may travel into the lower limb and even of nerve root compression.
past the knee into the lower leg and foot.
Grade 3: In this situation, tears have completely MECHANISM OF DISCOGENIC PAIN
disrupted the annulus and the PLL and deformed the In 1979, Brodsky and Binder83 characterized the mecha-
contour of the posterior portion of the disc. There is a full nism for the provocation of pain with discography.
thickness annular tear in which the outer annulus (Sharp- Their findings included: (1) stretching of the fibers of an
eys Fibers) and PLL have been completely ruptured. abnormal annulus, (2) extravasation of extradurally
During discography, contrast material leaks out of the irritating substances such as glycosaminoglycans, lactic
 Intervertebral Disc 27

posterior annular tears (a.k.a. IDD, radial fissures/

tears). Surprisingly, they discovered that the disc does
not have to be completely torn for the patient to suffer
from lower limb pain. In fact, discs did not even need to
be completely ruptured or bulging.
Grade 2 (outer annulus nonruptured and nonleak-
ing) were found to reproduce lower limb pain on dis-
cography just as often as grade 3 discs (bulging,
herniated, completely ruptured, and leaking). About
60% of both types of IDD reproduced lower limb
pains on provocative discography. This study supports
the theory that nuclear material in the outer region of
the posterior annulus may be a cause of sciatica on its
own.
The pain pathways for discogenic pain are still very
controversial. Traditionally, pain signals that originate
in the nerve roots adjacent to the disc move from that
root, into the corresponding dorsal root ganglion
(DRG) and into the spinal cord (Figure 14A). However,
recent new research suggests that pain signals from the
lower lumbar discs (L4 and L5) are detoured up the
sympathetic nerves (gray ramus communicans) and into
the upper lumbar DRGsespecially at the L2 level
(Figure 14B).8789 Clinically, in some patients it then
would be possible for patients with L4 and L5 disc
pathology to have L1 or L2 dermatomal pain (groin and
anterior thigh pain).

DIAGNOSIS OF IDD
Provocative Discography
The gold standard in making the diagnosis of IDD is a
very painful and invasive test called provocation discog-
raphy with follow-up CT discogram. There are two
components to provocation discography: the first is an
attempt by the physician to provoke the patient to feel
their usual pain (concordant pain) by pressurizing the
Figure 13. The classification of internal disc disruption from disc with a contrast material. The second is a painless
grade 0 to grade 5, based on the Modified Dallas Classification. discogram in the adjacent discs.
The International Society for the Study of Pain, in its
taxonomy,90 has adapted the following set of criteria for
acid, and acidic media, (3) pressure on nerves posteri- diagnosing IDD: (1) no visible disc herniations seen on
orly caused by bulging of the annulus, (4) hyperflexion magnetic resonance imaging (MRI) or CT, (2) during
of posterior joints on disc injection,84 and (5) the pres- provocation discography injection of the suspected disc,
ence of vascular granulation tissue, with pain caused by recreation of the patients exact back, and/or leg pain
scar distension.85 Another mechanism speculated was must occur,91,92 (3) injection of the disc above or below
pain generators in the end plates that may be provoked the suspect disc must be nonpainful, and this acts
by endplate deflection.86 as a control disc or normal disc, and (4) a grade 3 or 4
Ohnmeiss et al.86 studied the typical patterns of pain radial annular fissure must be demonstrated on CT
referral from different degrees of discogram-confirmed discography.9396
28 raj

A Gadolinium-DTPA Enhanced MRI

Although provocation discography with CT discogra-
phy is the gold standard to make the diagnosis of
symptomatic IDD, the procedure itself can damage the
disc and spread the degenerative disc disease.97102
As an alternative, the use of gadolinium (contrast)
enhancement may be considered. Gadolinium-
dimethoxypropane, when injected into the vein during
the MRI, will light up the granulation tissue that
forms within a healing/healed full thickness annular disc
tear (Figure 15A and B).

Hyper Intensity Zone

A hyper intensity zone is a focal high intensity signal in
the posterior annulus fibrosis distinct from the nucleus
without disc protrusion. This phenomenon also gives
another clue that IDD might be involved in the patients
pain syndrome, although this T2-weighted MRI finding
is highly controversial (Figure 16).
B

OPTIONS FOR TREATMENT OF DISCOGENIC PAIN

The Pathological Basis for some Low Back Pain may
be due to internally disrupted intervertebral discs and
in particular, sensitized annular tears. Treatments
described to manage IDD and discogenic pain include
surgical intervention with total disc excision and
arthrodesis or more conservative measures such as in-
tradiscal steroids, chemonucleolysis, intradiscal decom-
pression, annuloplasty, and the use of intradiscal laser
devices.
Two minimally invasive procedures have been pro-
moted as alternatives to major surgical interven-
tions. Both involve the introduction of a flexible
electrode into the painful disc, with the aim of
coagulating the posterior annulus. In addition, new
minimally invasive procedures have been introduced
to decompress the disc with painful pathology. A
classification of such percutaneous procedures is given
below.
1. Annuloplasty
Figures 14. Pain pathways for discogenic pain. (A) Pain signals A. Intradiscal electrothermal therapy (IDET)
that generate from the disc traverse pass into the corresponding
B. Radiofrequency posterior annuloplasty (RFA)
DRG and into the spinal cord. (B) Pain signals from the lower
lumbar discs (L4-L5) detour up the sympathetic nerves (grey C. Biacuplasty
ramus communicans) into the upper lumbar DRG, especially at 2. Percutaneous disc decompression
the L2 level. DRG, dorsal root ganglion. A. Laser discectomy
B. Radiofrequency coblation (plasma discec-
tomy)
 Intervertebral Disc 29

Figure 15. (A) MRI with a disc lesion. (B)

Enhanced MRI with Gadolinium-DTPA.
The enhanced MRI lights up the
granulation tissue in the full thickness
annular disc tear. MRI, magnetic reso-
nance imaging; DTPA, dimethoxypro-
pane.

form of oral analgesics, gentle traction, and nondynamic

spinal stabilization treatments and exercise.

1. Chemonucleolysis
In the early 1940s, chymopapain was derived from the
papaya fruit by Jansen and Balls, as reported by Jaiku-
mar, Kim, Kam, and Maroon.103,104 By 1956, Thomas
saw the potential for this enzymatic substance and
began work on determining a clinical use. He injected
the chymopapain intravenously into the ears of rabbits
and noted that the ears became floppy.105 Thomas con-
firmed the softening of the cartilaginous material in the
ear due to the chymopapain. Smith et al. picked up the
torch and hypothesized that chymopapain could be used
to treat chondroblastic tumors, which it did not;
however, they did find that when injected into the intra-
discal space of rabbits, the nucleus pulposus disap-
peared but left the annulus intact.104,105 In 1963, Smith
injected the first human patient with chymopapain to
Figure 16. T2-weighted MRI shows a hyper intensity zone (HIZ) treat sciatica. Chymopapain works by depolymerizing
in the posterior annular fibrosis, which is distinct from the signal the proteoglycan and glycoprotein molecules in the
from the nucleus. MRI, magnetic resonance imaging.
nucleus pulposus.104 These large molecules are respon-
sible for water retention and turgidity. When exposed to
C. Mechanical disc decompression (dekom- chymopapain, the water content within the disc plum-
pressor) mets; shrinkage follows and causes a reduction in disc
D. Manual percutaneous lumbar discectomy height and girth. The bulging disc, therefore, shrinks.
(PLD)
3. Endoscopic percutaneous discectomy Procedure
The patient is placed in either a lateral or a prone
Conservative Management position. Under conscious sedation and guided by fluo-
Ninety percent of all IDD patients will obtain satisfac- roscopy, a 6-inch, 18-gauge needle is inserted posterolat-
tory pain relief by conservative measures. However, for erally and placed centrally within the disc. Discography,
the conservative treatment to be effective, it may take along with the pain provocation test, is performed for
many months. Conservative treatment often takes the evaluation of the affected disc. Chymopapain is then
30 raj

injected into the nucleus pulposus in amounts ranging and in the hernia zone. The injection itself, except for a
from 1000 to 4000 U. The number of units injected slight sense of localized pain of short duration, is gen-
decreases if more than one disc is to be treated.104,105 erally painless and well-tolerated. There is insufficient
Chymopapain has been in use for more than 30 years. published data to conclude that this technique is a
After approval by the U.S. Food and Drug Administra- promising alternative method.
tion in 1982, early complications were reported even
though studies had shown a very safe record.105 Anaphy- MINIMALLY INVASIVE PROCEDURES
laxis, reported in 1% of cases, proved to be the most 1. Annuloplasty
severe complication.105 It became clear that good patient
1A. IDET. Intradiscal electrothermal therapy was
selection, proper surgical training and technique, preop-
developed and published by Saal and Saal in 2000 to
erative hypersensitivity testing and antihistamine admin-
serve as an alternative to fusion for patients with
istration could greatly reduce the complication rate when
chronic discogenic low back pain.108,109 There are several
using chymopapain. In fact, complications became
proposed causes for discogenic back pain. Some have
almost nonexistent in the late 1980s and 1990s when
stated that discogenic back pain is due to an IDD, most
utilizing the aforementioned criteria.
likely due to annular tears or fissures.104 Others feel the
Indications for chymopapain include those patients
discogenic pain may be a result of degenerative disc
who present with radicular pain as the chief complaint;
disease.106 Even the developers of the current IDET pro-
confirmation of the disc herniation via MRI, CT, or
cedure state that the pathophysiology of discogenic pain
myelogram; and patients having failed conservative
is complex and hard to pin down into one complete
treatment.104106 Kim et al. found that patients with
moderate to severe positive straight leg raise had a sig- and true definition.108 What is agreed upon is that the
nificantly higher success rate as compared to those with intervertebral disc, particularly the annulus, has noci-
ceptive nerve receptors, which increase when the disk
no or mild straight leg raising pain.106 The younger the
patient, the better the outcome. Younger patients had a degenerates, is injured, or is exposed to a variety of
success rate ranging from 82.3% for those in their 30s inflammatory substances. This increase in neural pain
to 94.6% for those in their teens. Patients 50 years and receptors causes increased and unremitting low back
older had only a 71% success rate.107 Those patients in pain.108,110,111 IDET was therefore developed to modify
whom the pain provocation test was positive had a collagen, making collagen thicker and causing it to con-
91.7% success rate compared to those who did not tract, decreasing the bodys ability to revascularize.
experience pain provocation at a 73.1% success rate.106
Chemonucleolysis has been fraught with controversy Procedure. This procedure is performed with fluoro-
since FDA approval. There are those who want to dismiss scopic guidance, while the patient is under conscious
the procedure as dead due to complications in earlier use sedation lying prone. As with many intradiscal proce-
(and lack of manufacture and distribution within the dures, discography, along with the pain provocation
U.S.A. since 1999), but there are others who state that test, ensues for evaluation of the affected disc. A
with the proper inclusion criteria, preprocedure testing, 17-gauge needle is then inserted posterolaterally into the
and good technique, chemonucleolysis has a significant disc, generally from the patients less painful side. A
place in the minimally invasive category.104106 30 cm catheter with a flexible 5 to 6 cm heating tip is
threaded circumferentially into the disc through the
2. Ozone Chemonucleolysis nucleus pulposus to the pathologic area of the annulus
Another alternative therapy that has been receiving (Figure 17). After fluoroscopic confirmation, the cath-
some interest in Europe is the use of medical ozone in eter tip is heated to 90C over a 13-minute period. Once
the treatment of herniated intervertebral discs.107 This at 90C, the temperature is maintained for an additional
therapy was developed by C. Verga in 1983. In the study four minutes. The catheter and needle are then removed.
of 15 years of treatment, Verga stated that the relapse of The patient is then observed in a recovery area before
pain occurred in less than 2% of cases. The method being discharged home the same day.108,110,111
involves the administration of 40/60 ml of ozone gas Indications for the IDET include long-term low back
(O2O3 mixture) at a concentration of 20/30 micro- pain, failure of conservative therapy, normal neurologic
grams per ml, repeated eight to 14 times. The injection exam, negative straight leg raise, MRI confirmation of
is generally made into the paravertebral musculature, no neural compressive lesion, and positive pain provo-
 Intervertebral Disc 31

Figure 17. Cephalocaudal view of the Spine-CATH in the L4-L5,

created by the curvature of the Lumbosacral spine in an antero- B
posterior radiographic image, showing the correct placement of
the catheter for the IDET procedure. IDET, intradiscal electrother-
mal therapy.

cation test.111 Exclusion criteria include inflammatory

arthritis, nonspinal conditions that mimic lumbar pain,
and any medical or metabolic condition that would
preclude proper follow-up.108,111,112 Much debate still
centers on this technique, as there have been limited
independent studies and studies reporting long-term
follow-up of patients receiving IDET.108,109,113 The col-
lagen modification could also lead to a reduction in the
size of annular fissures and increase the stability of the
disc itself.108,110 IDET also thermocoagulates the nocice-
ptors within the annular walls, thus destroying the Figure 18. This figure illustrates the technique of Radiofre-
ability to transmit nociceptive input.110,111 quency Annuloplasty. (A) The discTRODETM (Valleylab, Boulder,
Complications include catheter breakage, nerve Colorado) is inserted posterolaterally in the posterior annulus for
this technique. (B) RF catheter electrode system uses heat to
root injuries, post-IDET disc herniation, cauda equina coagulate and decompress disc material (Courtesy of Valleylab,
syndrome, infection, epidural abscess, and spinal cord Boulder, Colorado).
damage.
The evidence for IDET is moderate in managing
chronic discogenic low back pain. Both a mild sedative and a local anesthetic may be used
to reduce any discomfort the patient might experience.
1B. RFA. Radiofrequency annuloplasty is a minimally Using X-ray guidance, the physician will insert
invasive method of delivering RF thermal energy to the discTRODE cannula into an intervertebral disc
the disc to treat lower back pain. The discTRODE (Figure 18A). The catheter electrode is passed through
(Valleylab, Boulder, CO, U.S.A.) RF catheter electrode the cannula into the outer disc tissue (Figure 18B). RF
system uses heat to coagulate and decompress disc mate- current flows through the electrode, heating the tissue
rial, providing effective pain relief. Ideal candidates for directly adjacent to the active tip of the electrode to a
a discTRODE procedure are patients with chronic specific treatment temperature. An additional external
low back pain that one has determined to be the result temperature monitor allows the physician to continu-
of an internally disrupted disc. ously observe temperature changes in surrounding tissue
throughout the procedure.
Procedure. The discTRODETM procedure is typically Complications are similar to IDET with catheter
performed on an outpatient basis in a clinical setting. breakage, nerve root injuries, discitis, disc herniation,
32 raj

cauda equina syndrome, infection, epidural abscess, and

spinal cord damage.114,115

1C. Biacuplasty. The new annuloplasty procedure

termed intradiscal biacuplasty (Baylis Medical Inc.,
Montreal, Canada) utilizes a bipolar system that includes
two cooled, RF electrodes placed on the posterolateral
sides of the intervertebral annulus fibrosus. Kapural and
Mekhail reported on a young man with severe axial
discogenic pain treated with this procedure.116 The elec-
trodes are placed fluoroscopically. Two 17-gauge trans-
discal introducers were placed in the posterior annulus
using posterolateral, oblique approach. Then, RF probes
were positioned through each of the introducers bilater-
ally to create a bipolar configuration. There was a
gradual increase of the temperature of the electrodes to
55C over 11 minutes. There were no intraoperative
complications. Following the completion of the proce-
dure, the patient was monitored for 45 minutes then
discharged home. The patient was followed over a period Figure 19. Device used for the LASE procedure (Clarus
of 6 months. Outcome assessment included SF-36 and Medical).

Oswestry questionnaires. Visual analog scale (VAS) pain

scores changed from 5 (baseline) to 2 cm at 30 days and
1 cm at 6-month follow-up. Oswestry scale improvement disc to return to its normal state.119,120 If any disc mate-
was noted from 14 points prior to the procedure to 11 at rial needs to be removed, endoscopic tools can be used
1-month follow-up and 6 points at 6 months. to do so.
This procedure warrants future studies to determine
the efficacy, complication rates, and possible compara-
Procedure. The patient is placed in a prone or lateral
tive advantages of this procedure with other minimally
position under conscious sedation. An 18-gauge 7-inch
invasive procedures for disc lesions.
needle is introduced just anterior to the superior articu-
lar process and superior to the transverse process via
2. Percutaneous Disc Decompression a so-called triangular safe zone. Using fluoroscopy,
2A. Laser Discectomy (Figure 19). Medical lasers the needle is placed 1 cm beyond the annulus into the
have been used since the early 1960s. Ascher, Choy nucleus pulposus just parallel to the disc axis, preferably
et al. published their experiences with the use of halfway between the superior and inferior endplates. If
a neodymium : yttrium-aluminum-garnet (Nd : YAG) the procedure is endoscopically assisted, dilators are
laser on the lumbar spine for nucleolysis.117 There placed over the guide needle for visualization and the
are several types of lasers in use for the lumbar spine introduction of the endoscope. Irrigation with saline
with the most common being the holmium : yttrium- allows for better visualization of the spaces. Depending
aluminum-garnet (Ho : YAG) laser, the others are on the type, the laser is either fired as a pulse or con-
potassium-titanyl-phosphate, and the neodymium tinuously. The Ho:YAG laser is pulse-fired. Newer laser
(Nd) : YAG laser. The Ho : YAG laser is most com- models offer side-firing capabilities. This advancement
monly paired with the endoscope for disc ablation and helps to provide more control of laser placement, better
removal capabilities.118,119 This laser-assisted technique observation, and can help reduce the risk of injury to
combines two effective but limited approaches. several areas, especially those anterior to the spinal
As the affected tissues absorb the laser, light is con- column. Larger fragments, which are more difficult to
verted to heat. At 100C, tissue vaporizes and ablation remove through the endoscope, can be laser ablated.
takes place. As a small amount of nucleus pulposus is After firing the laser and adequate nucleus pulposus
vaporized, intradiscal pressure decreases, allowing the has been removed/ablated, the laser and dilators are
 Intervertebral Disc 33

gas, which is removed through the needle. As the wand

is withdrawn, coagulation takes place thermally treating
the channel, which leads to a denaturing of nerve fibers
adjacent to the channel within the nucleus pulposus.
This process is repeated up to six times within an indi-
vidual disc. The patient is then sent to recovery and later
sent home the same day.
Indications for this procedure include low back pain
with or without radiculopathy, MRI confirmation of
contained herniated disc, and failed conservative
therapy. Patients who should be excluded from receiving
Figure 20. Radiofrequency Coblation (plasma discectomy) (Arth- this procedure include those with spinal stenosis, a loss
roCare, Sunnyvale, CA, U.S.A.) coagulation channels within the of disc height of 50%, severe disc degeneration, spinal
nucleus Pulposus after ablation. fracture or tumor.

removed. The incision can be closed with sutures or

surgical adhesives. The patient is moved to recovery and 2C. Mechanical Disc Decompression (Dekompressor).
sent home later in the day. Few changes have been made in automated discectomy
Indications for laser discectomy include those with until recently with innovations in automation. The
back and leg pain with a confirmed disk herniation. A newest entry is the Dekompressor (Stryker Corpora-
ruptured annulus and lateral recess stenosis are not con- tion, Kalamazoo, MI, U.S.A.) introduced in 2002.122 The
traindications. Newer Transforaminal procedures can Dekompressor is a disposable, self-contained, battery-
treat those patients with fragments in the epidural space. operated hand piece connected to a helical probe (Fig-
In 2002, Tsou and Yeung reported the 9-year retro- ure 21). The outer cannula measures 1.5 mm with an
spective results of their percutaneous transforaminal inner rotating probe. When activated, the probe rotates
approach, with an 88.1% excellent to good result.120
Other studies report success rates from 78% to 85% in
retrospective studies.121 There is a scarcity of clinical
trials regarding percutaneous lasers. Negative aspects of
the laser include a steep learning curve for the physician.
The use of lasers coupled with an endoscopic approach
significantly increases the difficulty level for the surgeon.

2B. RF Coblation (Plasma Discectomy). Radiofre-

quency Coblation (plasma discectomy) (ArthroCare,
Sunnyvale, CA, U.S.A.) is another procedure that has
broken into the minimally invasive field in the 21st
century. The first Nucleoplasty was performed in 2000.

Procedure. Radiofrequency Coblation combines disc

removal and thermal coagulation to decompress a
contained herniated disc. With the patient in a prone
or lateral position under sedation, a posterolateral
approach guided by fluoroscopy is made with a
17-gauge obturator stylet. A discogram may take place
at this time to confirm location and for a positive provo-
cation test. Taking care not to contact the anterior
Figure 21. Placement of the needle into the inflamed disc with
annulus, the nucleus pulposus is first ablated with RF
the posterolateral approach for mechanical disc decompression
waves as the wand (Figure 20) is advanced causing a in a model skeleton (with permission from Stryker Corp., Kalama-
molecular dissociation process converting tissue into zoo, MI, U.S.A.).
34 raj

creating suction to pull milled nucleus pulposus from the is pedal activated, is gently moved back and forth within
disk up the cannula to a suction chamber at the base of the disc until no more disc material is aspirated and then
the handheld unit. Approximately 0.5 to 2 cc of nucleus the probe is rotated. When aspirated disc material
pulposus is removed. This efficient removal of disc mate- decreases significantly, the probe is removed from the
rial decreases surgical procedure times to approximately disc space, usually within 20 to 40 minutes.126128
30 minutes; with the actual time of use for the probe
not exceeding 10 minutes. This procedure is performed 3. Percutaneous Endoscopic Discectomy
under fluoroscopic guidance. The Dekompressor tech- Burman in 1931 was the first reported author who
nique specifically has yet to be studied in a controlled introduced the concept of the direct visualization of the
clinical trial and results with this new automated tech- spinal cord. A few years later, Mixter and Barr performed
nique are limited. Percutaneous discectomy generally has an open laminectomy with discectomy for the treatment
a reported success rate of 60% to 87% good outcomes.123 of a disc herniation into the spinal canal.129 Later, Pool
introduced the concept of intrathecal endoscopy and
2D. Manual PLD. Percutaneous lumbar discectomies reported the outcomes of more than 400 myeloscopic
have been performed for more than 30 years with procedures.130 Due to surgical complications of intraspi-
overall results ranging from disappointing to good nal surgery, endoscopy remained forgotten until the
results. The techniques and equipment used for percu- work carried out by Ooi et al. during the 1970s.131
taneous discectomy vary widely and have fallen in and Hijikata et al. in 1975 demonstrated a percutaneous
out of favor. Hijikata et al. first reported performing a nucleotomy by means of arthroscopy instruments for
percutaneous nucleotomy in 1975.124 The procedure disc removal for the treatment of posterior or postero-
included the use of 3 to 5 mm cannulas from the pos- lateral lumbar disk herniation under local anesthesia.132
terolateral approach, curettes, and time-consuming Kambin described the safe triangular working zone
manual removal of the nucleus pulposus with pituitary (Kambins triangle) and results of arthroscopic micro-
forceps. The theory was that the reduction of Intradiscal discectomy, in which arthroscopic visualization of the
pressure would reduce irritation of the nerve root and herniation via the posterolateral approach was used
the nociceptive nerve receptors in the annulus. The pro- for discectomy of contained herniations (Figure 22). In
cedure remained limited in use until 1985, when Onik 1985, Onik et al.133 reported the development of a 2 mm
et al. developed a new and smaller type of aspiration
probe, which reduced risk of injury to the peripheral
nerves and the annulus, facilitated easier removal of
the nucleus pulposus with an all-in-one suction cutting
device, and decreased surgical time.125

Procedure. Both procedures use a posterolateral

approach to the affected disc on an outpatient basis. The
automated procedure is performed while the patient is
in a lateral decubitus or prone position. An 18-gauge
hubless sheath with a central trocar is guided toward the
affected disc. The trocar is removed and a smaller
2.5 mm cannula with an inner blunt end sleeve is placed
over the hubless sheath. Once correct placement is con-
firmed, the hubless sheath is removed, leaving the
2.5 mm cannula. A 2 mm saw is threaded through the
cannula and a hole is cut into the annulus for the aspira-
tion probe to be inserted. The aspiration probe is a
sharpened cannula fitted through an outer needle. Using
suction to pull in disc material, the inner, sharpened
cannula uses a slide-like cutting motion to slice the tissue
Figure 22. Lumbar Epidural Endoscopic procedure performed:
which is then aspirated, along with irrigation, through technique of passing the cannula and other instruments in the
the inner cannula to a collection bottle. The probe, which disc space.
 Intervertebral Disc 35

blunt-tipped suction cutting probe for automated per- mally visualize the disc space. The cannula puncture site
cutaneous diskectomy at L4-L5 or higher levels. should be made between the carotid sheath and the
airway. The carotid pulse at the disc level is then pal-
Transforaminal Endoscopic Microdiscectomy. The pated with the index and middle fingers, and the carotid
technique of foraminal epidural endoscopic discectomy sheath structures are displaced laterally by manual
(FEES) was developed from epidural endoscopy. FEES palpation.
differs from other percutaneous discectomy procedures
in that direct visualization of the epidural space, the OUTCOME
pathology, and neuroanatomic structures is possible.134 One large-scale prospective nonrandomized investiga-
Recently, the use of spinal endoscopy has been tion followed 402 patients who were treated for
enlarged to include closed decompression of spinal disc herniation-associated sciatica.135 Two groups were
roots, use with lasers, epidural biopsies, percutaneous formed: The first consisted of 220 patients who had
interbody fusion, and lysis of epidural adhesions. undergone surgery; the second consisted of 182 patients
As with other forms of minimally invasive surgical who had chosen to be conservatively (nonsurgically)
disc procedures, patient selection is critical. Patients treated. This study demonstrated that surgical treatment
should have leg pain more severe than back pain and for disc herniation-associated sciatica is faster and
6 months of failed conservative therapy. The ideal slightly more effective than conservative nonsurgical
pathology is a virgin (previously unoperated) paramed- conservative care. There have been reports of more than
ian, foraminal, or extraforaminal contained herniation, 7000 automated or manual PLD procedures performed.
or one that is noncontained at less than 50% of the Published results indicate an overall success rate of 75%
canal diameter. with a complication rate of 1%.

Regional Endoscopic Techniques Evaluation of Intradiscal Therapies

Lumbar Discectomy. This is currently the ultimate IDET. Appleby et al.,136 in a systematic review of the
form of minimally invasive spine surgery. In this tech- literature in 2006, concluded that there was compelling
nique, an endoscope is used. The whole procedure is evidence for the relative efficacy and safety of IDET.
performed under local anesthesia and the patient is fully Freeman137 performed a critical appraisal of the evi-
awake during surgery. The patient is made to lie prone dence of IDET (also published in 2006) and concluded
on the operating table. An exact entry point is mapped that the evidence for the efficacy of IDET remains weak
on the patients body using an image intensifier X-ray and has not passed the standard of scientific proof. The
system and a long spinal needle is introduced from the present evidence includes one positive randomized trial,
posterolateral aspect of the lumbar spine. Through this one negative randomized trial, seven positive prospec-
needle, a guide wire is inserted. Then, a 5 mm incision tive evaluations,138144 and two negative reports.145,146
is made on the skin. Following that, a dilator and a The evidence for IDET is moderate in managing chronic
working cannula are inserted under local anesthesia, discogenic low back pain.
through which the endoscope is passed. The camera and
monitor attached to the endoscope allow the prolapsed Disctrode Procedure. Finch et al.147 studied 31 patients
part of disc to be removed under direct vision. The by heating annular tears with a flexible RF electrode
wound is closed with a single stitch. The patient usually placed across the posterior annulus and compared them
gets immediate pain relief and can go home in 24 h. to 15 patients receiving conservative management. The
VAS decreased significantly. The evidence for RFA was
Cervical Discectomy. The discs in the cervical region limited for short-term improvement, and indeterminate
cannot be approached posteriorly (because of the spinal for long-term improvement in managing chronic disco-
cord), anteriorly (because of the airway), or posterolat- genic low back pain.
erally (because of the vertebral artery and the uncinate
process). Many authors believe that a right-sided Percutaneous Disc Decompression. Waddell et al.148 in
approach should always be used for right-handed prac- a systematic review based on Cochrane Collaboration
titioners and a left-sided approach when left-handed. Review and meta-analysis of surgical interventions in the
The C-arm is placed in the anterior-posterior position lumbar spine,149 identified three trials comparing auto-
with cranial or caudal angulation of the C-arm to opti- mated PLD (APLD) with other surgical techniques and
36 raj

concluded there was limited and contradictory evidence. domized trials. The evidence is moderate for short-term
Randomized trials of APLD and microdiscectomy and limited to long-term relief.154159
included Chatterjee et al.150 and Haines et al.151 Chatter-
jee et al. compared APLD with microdiscectomy in the Plasma Discectomy. There were no systematic reviews
treatment of contained lumbar disc herniation in a ran- evaluating the effectiveness of Nucleoplasty thus far
domized study with blind assessment. The study included in the literature. The effectiveness of Nucleoplasty has
71 patients with radicular pain as their dominant been reported in six prospective studies.160165 Sharps
symptom after failure of conservative therapy for at least and Isaac evaluated 49 patients.161 The evidence of
6 weeks and with MRI demonstration of contained disc Nucleoplasty is limited for short- and long-term relief.
herniation at a single level with a disc bulge of less than
30% of the canal size. The study excluded patients with
dominant symptoms of low back pain, disc extrusion, Mechanical Disc Decompression. There have been no
sequestration, subarticular or foraminal stenosis, or mul- systematic evaluations of percutaneous disc decompres-
tiple levels of herniation. The results showed satisfactory sion utilizing DeKompressor. There also have not been
outcomes in 29% of the patients in the APLD group and any guidelines describing this technology. Amoretti
80% of the microdiscectomy group. They concluded that et al.162 published results of a clinical follow-up of 50
APLD was ineffective as a method of treatment for small, patients treated by PLD using the DeKompressor.
contained lumbar disc herniations. Authors were criti- Although the study was not a blinded, randomized
cized in that they failed to utilize CT discography. study, the data collection was thought to be good. The
Haines et al. conducted a randomized study compar- evidence for percutaneous disc decompression utilizing
ing APLD to conventional discectomy as a first-line DeKompressor is limited for short- and long-term relief.
treatment for herniated lumbar discs.151 The study mea-
sured outcomes with physical signs related to the severity NEW THERAPIES
of low back pain and sciatica, but used a modified Roland Current treatments attempt to reduce pain rather than
Scale for disability assessment, and the SF-36 for general repair the degenerated disc. They are mainly conserva-
health status. The primary endpoint was the patients tive and palliative, and are aimed at returning patients
outcome ratings 12 months after surgery. The study to work. They range from bed rest (no longer recom-
included patients with unilateral leg pain or paresthesia mended) to analgesia, the use of muscle relaxants or
with no history of lumbar spinal surgery, whereas exclu- injection of corticosteroids, or local anesthetic and
sions included moderate or advanced lumbar spondylo- manipulation therapies. Various interventions (eg,
sis, spondylolisthesis, lateral restenosis, herniated disc Intradiscal electrotherapy) are also used, but despite
fragment occupying more than 30% of the AP diameter anecdotal statements of success, trials thus far have
of the spinal canal, herniated disc fragment migrating found their use to be of little direct benefit.144 Disc
more than 1 mm above or below the disc space, calcified degeneration-related pain is also treated surgically,
disc herniation, lateral disc herniation, or posterior disc either by discectomy or by immobilization of the
space height less than 3 mm. Success rate for APLD was affected vertebrae, but surgery is offered in only one of
41% compared with conventional discectomy at 40%. every 2000 back pain episodes in the U.K.; the incidence
However, they concluded that the study did not have of surgical treatment is five times higher in the U.S.A.166
power to identify clinically important differences because The success rates of all these procedures are generally
of insufficient patient enrollment. Among the prospective similar. Although a recent study indicated that surgery
evaluations and case series studies,152,153 all of them improves the rate of recovery in well-selected patients,167
reported positive results in greater than 50% of patients 70% to 80% of patients with obvious surgical indica-
in a large population. The evidence is moderate for tions for back pain or disc herniation eventually recover,
short-term and limited for long-term relief.154 whether surgery is carried out or not.168,169
Because disc degeneration is thought to lead to
Percutaneous Laser Discectomy. Based on the system- degeneration of adjacent tissues and be a risk factor in
atic review by Waddell,148 there is no acceptable evi- the development of spinal stenosis in the long term, new
dence for laser discectomy. Relevant studies evaluating treatments are in development that are aimed at restor-
the effectiveness of laser disc decompression included 14 ing disc height and biomechanical function. Some of the
studies meeting inclusion criteria. There were no ran- proposed biological therapies are outlined below.
 Intervertebral Disc 37

Oral Glucosamine and Chondroitin Sulfate Enhance pathogenesis of degeneration. In addition, the cell density
Proteoglycan Synthesis in normal human discs is low, and many of the cells in
These agents have been used in multiple trials for periph- degenerate discs are dead;20 stimulation of the remaining
eral joint osteoarthritis. These reports have generally cells may be insufficient to repair the matrix.176
been exaggerated by publication bias.170 There is, Cell implantation alone or in conjunction with gene
however, evidence that Glucosamine and Chondroitin therapy is an approach that may overcome the paucity
sulfate synergistically enhance the natural hypermeta- of cells in a degenerate disc. Here, the cells of the degen-
bolic repair response of chondrocytes and retard the erate disc are supplemented by adding new cells either
enzymatic degradation of cartilage. Derby et al. per- on their own or together with an appropriate scaffold.
formed a pilot study using Intradiscal injectable This technique has been used successfully for articular
Glucosamine and Chondroitin sulfate with DMSO (dim- cartilage177,178 and has been attempted with some success
ethylsulfoxide) and hypertonic dextrose to promote a in animal discs.179 However, at present, no obvious
reparative response in the intervertebral disc.171 They source of clinically useful cells exists for the human disc,
hypothesized that the reduction in the pain and disability particularly for the nucleus, the region of most inter-
seen in patients treated with Glucosamine and Chon- est.180 Moreover, conditions in degenerate discs, particu-
droitin mixtures results from favorable alteration in the larly if the nutritional pathway has been compromised,50
biochemical milieu of the intervertebral disc. Clinical may not be favorable for survival of implanted cells.
efficacy is similar to that of IDET procedures, but with an Nevertheless, autologous disc cell transfer has been used
improved costbenefit ratio. There is a need for con- clinically in small groups of patients,180 with initial
trolled randomized comparative studies to establish the results reported to be promising.
efficacy of intradiscal glucosamine and chondroitin S. Richardson, of the University of Manchester, in
sulfate injections. collaboration with Arthro Kinetics has successfully pro-
duced nucleus pulposus cells using mesenchymal stem
cells (MSCs).181 He has developed a clinical procedure to
Cell-Based Therapies inject these cells into the intervertebral disks, thus build-
The aim of these therapies is to achieve cellular repair of ing disk height and providing more cushion to degener-
the degenerated disc matrix. One approach has been to ated disks. This procedure involves mixing the MSCs in
stimulate the disc cells to produce more matrix. Growth a collagenous gel, and then implanting the gel in the
factors can increase rates of matrix synthesis by up to intervertebral disc via an arthroscopic procedure. The
fivefold.172,173 In contrast, cytokines lead to matrix loss idea of using ones own stem cells to regenerate a
because they inhibit matrix synthesis while stimulating dysfunctional intervertebral disc shows promise.
production of agents that are involved in tissue break- At present, although experimental work demon-
down.174 These proteins have thus provided targets for strates the potential of these cell-based therapies, several
genetic engineering. Direct injection of growth factors or barriers prevent the use of these treatments clinically.
cytokine inhibitors has proved unsuccessful because their Moreover, these treatments are unlikely to be appropri-
effectiveness in the disc is short-lived. Hence gene- ate for all patients; some method of selecting appropri-
therapy is now under investigation; it has the potential ate patients will be required if success with these
to maintain high levels of the relevant growth factor or therapies is to be realized.
inhibitor in the tissue. In gene therapy, the gene of interest
(eg, one responsible for producing a growth factor Augmentation of Nucleus Pulposus
such as transforming growth factor-b or inhibiting The objectives of augmentation of the nucleus pulposus
interleukin-1) is introduced into target cells, which following disc removal are to prevent disc height loss
then continue to produce the relevant protein.175 This and the associated biomechanical and biochemical
approach has been shown to be technically feasible in the changes. Free-flowing materials may be injected via a
disc, with gene transfer increasing transforming growth small incision, allowing minimally invasive access to the
factor-b production by disc cells in a rabbit nearly disc space. Fluids can interdigitate with the irregular
sixfold. However, this therapy is still far from clinical use. surgical defects and may even physically bond to the
Apart from the technical problems of delivery of the adjacent tissue. Injectable biomaterials allow for
genes into human disc cells, the correct choice of thera- incorporation and uniform dispersion of cells and/or
peutic genes requires an improved understanding of the therapeutic agents. Injectable biomaterials have been
38 raj

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