Spinal Disorders: Fundamentals of Diagnosis and Treatment Part 15 ppt

Key Articles
Kirkaldy-Willis WH, Wedge JH, Yong-Hing K, Reilly J (1978) Pathology and pathogene-
sis of lumbar spondylosis and stenosis. Spine 3(4):319 – 28
In this study, autopsy specimens of lumbar spines were used to define the degenerative
cascade of the spine. Progressive degenerative changes in the posterior joints lead to
destruction and instability. Similar changes in the disc result in herniation, internal dis-
ruption, and resorption. Combined changes in posterior joint and disc can produce
entrapment of a spinal nerve in the lateral recess and/or central stenosis. Changes at one
level often lead, over a period of years, to multilevel spondylosis and/or stenosis.
Miller JA, Schmatz C, Schultz AB (1988) Lumbar disc degeneration: correlation with age,
sex, and spine level in 600 autopsy specimens. Spine 13(2):173 –8
This meta-analysis is based on data from 16 published reports. Macroscopic disc degen-
eration grades were correlated with age, sex, and level in 600 lumbar discs from 273
cadavers (0–96 years of age). Male discs were significantly more degenerated than female
discs in the second, and fifth to seventh life decades. L4/L5 and L3/L4 level discs showed
more degeneration than other levels. Higher mechanical stress, perhaps combined with
longer nutritional pathways, may be responsible for the earlier degeneration of male
discs.
Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG (2002) 2002 Vo lvo
Award in Basic Science: Classification of age-related changes in lumbar intervertebral
discs. Spine 27(23):2631 – 44
This paper provides a systematic semiquantitative assessment of age-related morpho-
logic changes in the intervertebral disc and cartilaginous endplate which is based on
20250 histologic variables. The study revealed significant temporospatial variations
with regard to presence and abundance of histologic disc alterations across levels,
regions, macroscopic degeneration grades and age groups. The detailed analysis
resulted in a practicable and reliable histologic classification system for lumbar discs
which can serve as a morphologic reference framework. The article provides clear histo-
logic evidence for the detrimental effect of a diminished blood supply to the interverte-
bral disc that appears to initiate disc tissue breakdown beginning in the first half of the
second life decade.

HornerHA,PhilM,UrbanJPG(2001) 2001 Volvo Award Winner in Basic Science: Effect
of nutrient supply on the viability of cells from the nucleus pulposus of the interverte-
bral disc. Spine 26(23):2543 – 49
Nucleus pulposus cells were cultivated in a system where nutrient supply was dependent
on diffusion, therefore simulating the situation in the intervertebral disc. It was found
that the cell density was dependent on nutrient supply and was inversely related to disc
thickness. Oxygen supply was not necessary for cell viability but was needed for proteog-
lycan production. Lack of glucose or low pH led to cell death suggesting nutrient restric-
tions contribute to disc degeneration.
Roberts S, Urban JPG, Evans H, Eisenstein SM (1996) Transport properties of the human
cartilage endplate in relation to its composition and calcification. Spine 21(4):415 –20
Transport properties of solutes of different sizes and shapes were correlated with the
composition of the cartilage matrix. The more hydrated the matrix, the easier solutes
were found to move. Increasing contents of proteoglycan, collagen or calcification
resulted in greater restriction of solute movement. This finding confirmed that calcifica-
tion of the cartilage endplate might have consequences for the nutrient supply to the disc
and therefore for the onset of disc degeneration.
Weiler C, Nerlich AG, Zipperer J, Bachmeier BE, Boos N (2002) 2002 SSE Award in Basic
Science: Expression of major matrix metalloproteinases is associated with interverte-
bral disc degradation and resorption. Eur Spine J 11(4):308 – 20
The role of matrix metalloproteinases (MMPs) in matrix degradation leading to disc
degeneration was investigated in 30 cross-sections of lumbar intervertebral discs from
cadavers (0–86 years of age). Expression of major MMPs was found to correlate with age
and the occurrence of signs of degeneration, i.e. clefts and tears. These data indicated that
major MMPs play an important role in matrix degradation that might lead to disc degen-
eration and possibly to the induction of low back pain.
Age-Related Changes of the Spine Chapter 4 115
BattieMC,VidemanT,GibbonsLE,FisherLD,ManninenH,GillK(1995) 1995 Volvo Award
in Clinical Sciences. Determinants of lumbar disc degeneration. A study relating lifetime
exposures and magnetic resonance findings in identical twins. Spine 20(24):2601 – 12

Effects of lifetime exposure of 115 twin pairs to commonly suspected risk factors on disc
degeneration were assessed by magnetic resonance imaging and their influence was com-
pared to age and familial aggregation, reflecting genetic and shared environmental influ-
ences. The results of this study suggested that disc degeneration may be primarily
explained by genetic influences, with environmental factors, widely suspected of acceler-
ating disc degeneration, only having very modest effects.
Adams MA, Freeman BJC, Morrison HP, Nelson IW, Dolan P (2000) Mechanical initia-
tion of intervertebral disc degeneration. Spine 25(13):1625 –36
It was investigated whether minor damage to a vertebral body can lead to progressive dis-
ruption of the adjacent intervertebral disc. After cadaveric lumbar motion segments were
subjected to complex loading patterns to simulate typical activities, compressive damage
to the bony endplates was observed, altering the compressive stress distribution on the
adjacent disc. Further loading cycles resulted in progressive structural changes and dete-
rioration of the adjacent discs.
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122 Section Basic Science
5
Pathways of Spinal Pain
Heike E. Künzel, Norbert Boos
Core Messages
✔
Chronic (persistent) pain has a high prevalence
in the general population and is predominately
felt as musculoskeletal pain
✔
A temporal classification of pain (i.e. acute, sub-
acute, chronic) is arbitrary and does not reflect
the underlying mechanisms of pain
✔
Pain is better differentiated into nociceptive,
inflammatory, and neuropathic pain
✔
Neuropathic pain has lost its protective role
and is maladaptive
✔
The physiologic processes involved in pain can
be differentiated into transduction, conduction,
transmission, modulation, projection and per-
ception
✔
Nociceptive signals are modulated by various
excitatory and inhibitory mechanisms on their
pathways to the brain
✔

Genetic predisposition and biopsychosocial fac-
tors have a significant influence on pain per-
ception
✔
Pain pathways can undergo distinct alterations
as a result of peripheral tissue damage and
neural injuries (neuroplasticity)
✔
The neuroplasticity of the pain pathways can
be described in terms of peripheral sensitiza-
tion, transcriptional changes in the dorsal root
ganglion, central sensitization and disinhibition
✔
Persistent pain is not prolonged acute pain but
follows distinct alterations in the pain pathways
✔
Neuropathic pain is different from nociceptive
pain and results from primary damage or dis-
ease of the peripheral or central nervous system
✔
Not all persistent pain is neuropathic. The clini-
cal differentiation of persistent inflammatory
and neuropathic pain, however, remains a chal-
lenge
✔
Treatment of acute pain should be aggressive,
multimodal and preemptive to avoid pain per-
sistence
✔
Adjuvant drugs (e.g. antidepressants, anticon-

vulsants, anxiolytics) enhance the central effect
of analgesics and should be included for an
adequate treatment of moderate to severe pain
✔
The scientific evidence for a long-term effec-
tiveness of surgical treatment of persistent spi-
nal pain is lacking
Historical Background
Precartesian Theories
Pain remained enigmatic
in ancient times
Early civilizations provided a wide variety of explanations for pain and attrib-
uted it to factors such as religious influences of gods, the intrusion of magical flu-
ids, the frustration of desires and deficiency or excess in the circulation of Qi
[70]. The relief of pain therefore was the task of shamans or priests, who used
herbs, rites, and ceremonies to alleviate pain. The early Greeks gave more specific
explanations for pain [70]. According to Plato (427–347
A.D.), the heart and the
liver were the centers of appreciation of all the sensations, and pain arose not
only from peripheral sensation but as an emotional response in the soul, which
was located in the heart [70]. Hippocrates assumed a wrong mixture of fluids to
be the cause of pain. However, Galen of Pergamon (130–200
A.D.)madethefirst
observations on the nervous system and the spine but still believed the so-called
“fluid doctrine” of Hippocrates (see Chapter
1 ).
Basic Science Section 123
Cartesian Theory
Descartes first suggested
a pathway which transmits

noxious stimulus directly
to the brain
The French philosopher Ren´e Descartes (1596–1650) presented a dualistic view
of the human body and soul,i.e.heassumedaseparationofthemindandthe
body. The body was seen as a machine working according to the laws of nature
and the “rational soul” was the “conductor of the orchestra” [70]. With the sug-
gestedseparationofthesoulfromthehumanbody,anendlesscontroversyarose
about the mind-body relation which has been plaguing and intriguing philoso-
phers and neuroscientists ever since [7]. Descartes also proposed a simple path-
way of the transmission of a noxious stimulus to the brain [22]. However,Descar-
tes’ theory was only published after his death in the Trait ´edel’Homme[7]. Des-
cartes gave a purely mechanical view of the involuntary withdrawal of a foot that
comes into contact with a noxious stimulus: “the small rapidly moving particle of
fire moves the skin of the affected spot causing a thin thread to be pulled. This
opens a small valve in the brain and through it animal spirits are sent down to the
muscles which withdraw the foot” [22]. After that it was believed for a long time
that there was a one-to-one relationship between the amount of damage and the
perceived pain. The theory of Descartes implies that a specific pain pathway car-
riesthemessagefromapainreceptorintheskintoapaincenterinthebrain.
However, it has become apparently clear that pain cannot be alleviated by simply
cutting this pathway. On the contrary, a dissection of this pathway can even exac-
erbate the pain [22].
Gate Control Theory
Neural “gates” transmit
or block nociceptive
transmission to the CNS
Major progress in our understanding of pain and its mechanisms followed the
introduction of a new theory by Melzack and Wall in 1965 [77]. The authors sug-
gested a gate control system which modulates sensory input from the skin before
it evokes pain perception and response. Accordingly, the substantia gelatinosa in

the dorsal horn functions as a gate control system that modulates the afferent
patterns before they influence the central transmission cells. The afferent pattern
in the dorsal column system acts as a central control trigger which activates
selective brain processes that influence the modulation properties of the gate
control system. The transmission cells activate neural mechanisms which com-
promise the action system responsible for response and perception [77]. This
theory underwent multiple modifications and extensions throughout the follow-
ingyears.Althoughithasbeenshownthatspecificelementsofthegatecontrol
theory are invalid or too simplistic, the fundamental model remains. Gates in the
dorsal horn consisting of interneurons balance the level of sensory fiber activity
and are influenced by descending brain signals. This concept explains how pain
can be felt with and without tissue damage and how psychological factors can
influence pain [84].
Modern Pain Theories
Since the introduction of Melzack and Wall’s theory, most of the research has
focused on two general processes that can control the pain gate [19], i.e.:
the inhibitory mechanism
the exhibitory mechanism
Pain has a morphological
and molecular correlate
Inhibitory neuronal circuits control nociceptive transmission in the spinal cord
and act as gatekeepers suppressing undesirable inputs [19], while increased exci-
tation can occur as a result of neural plasticity [130]. In the last decade, intriguing
progress has been made in dissecting out the molecular and cellular mechanisms
124 Section Basic Science