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8/13/2019 Clin Anat 07 Spinal Segmental Bone Innervation
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REVIEW
The Evidence for the Spinal SegmentalInnervation of Bone
JASON J. IVANUSIC*
Department of Anatomy and Cell Biology, University of Melbourne, Victoria, Australia
Dermatomes and myotomes are areas of skin and muscle, respectively, thatare innervated by single spinal segmental nerves, and reflect a principle of or-ganization that appears in just about every clinical textbook available today.The evidence for the existence of dermatomes and myotomes has a long andsubstantial history. A lesser known, but similar principle exists for the skeletalsystem. The term sclerotome was first used in the non-embryological sense
by Inman and Saunders ([1944] J. Nerv. Ment. Dis. 99:660667) to define aregion of bone and periosteum that is innervated by a single spinal segment.It is used by clinicians in many healthcare settings to aid in the diagnosis anddescription of a variety of deep and/or skeletal tissue pathologies and painsyndromes. In this article, the evidence for the existence of the sclerotomes isdescribed in detail. Early clinical studies that define the sclerotomes, evidencefrom studies of the development of skeletal innervation, and the contributionsof anatomical and physiological investigations are explored. It is suggestedthat there is in fact little direct evidence for the existence of discrete spinalsegmental innervation patterns for the skeleton. Clin. Anat. 20:956960,2007. VVC 2007 Wiley-Liss, Inc.
Key words: sclerotomes; segmental innervation of bone; skeletal innervation
INTRODUCTION
Dermatomes and myotomes are areas of skin and mus-
cle, respectively, that are innervated by single spinal seg-
mental nerves, and reflect a principle of organization that
appears in just about every clinical textbook available
today. Whilst textbook descriptions are often simplistic (for
example, they fail to account for considerable overlap in
territories innervated by adjacent spinal nerves), they are
used widely by clinicians in many healthcare settings to aid
in the diagnosis and description of a variety of conditions.
The evidence for the existence of dermatomes and myo-tomes has a long and substantial history (Warwick et al.,
1989; Greenberg, 2003).
A lesser known, but similar principle exists for the skele-
tal system. The term sclerotome was first used in the non-
embryological sense by Inman and Saunders (1944) to
define a region of bone and periosteum that is innervated
by a single spinal segment. This definition appears as a sec-
ondary meaning in (some) medical dictionaries. The pri-
mary use of the term by most anatomists and clinicians is
in descriptions of the ventromedial part of the embryologi-
cal somite, which ultimately forms the axial skeleton (see
Evidence From Developmental Studies). This embryologi-
cal definition cannot extend to the adult because the group
of cells that constitute the somite do not exist beyond the
embryonic stage, and the definition of Inman and Saunders
cannot be applied to the early stages of development
because the innervation of skeletal tissue is yet to fully de-
velop. To avoid ambiguity in the present review, the term
sclerotome is used to define a region of bone and perios-
teum innervated by a single spinal segment. When referring
to the embryological meaning, the term embryological
sclerotome is used. The same convention is applied to the
terms dermatome and myotome.A number of clinicians have used the sclerotomes, as
defined by Inman and Saunders (1944), in early discus-
*Correspondence to: Dr. Jason Ivanusic, Department of Anatomyand Cell Biology, University of Melbourne, Melbourne, VIC 3010,Australia. E-mail: j.ivanusic@unimelb.edu.au
Received 25 March 2007; Revised 15 August 2007; Accepted 4September 2007
Published online 22 October 2007 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ca.20555
VVC 2007 Wiley-Liss, Inc.
Clinical Anatomy 20:956960 (2007)
8/13/2019 Clin Anat 07 Spinal Segmental Bone Innervation
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sions of backache (Rose, 1954; Wilson, 1967), cancer
(Klingon, 1961, 1964), fibrositis (Yunus et al., 1981), herni-
ated discs (Inman and Saunders, 1947), referred and deep
pain (Southworth and Krohn, 1950), nerve blocks to treat
pain (Dobney and Belam, 1963), and more recently, in dis-
cussions of bone disorders such as melorheostosis (Murray
and McCredie, 1979; North and McCredie, 1987) and thali-
domide induced malformations (McCredie, 1977; McCredieet al., 1984; McCredie and Willert, 1999). Chiropractors
today use published maps of sclerotomes in describing
deep, scleratogenous pain (Banner-Therapy-Products-
Inc., 2007). However, upon reviewing the literature, few
studies of the spinal segmental innervation of bone
could be found. In this article, the evidence for the exis-
tence of the sclerotome is reviewed. It is suggested that
there is in fact little direct evidence for the existence of the
sclerotome.
CLINICAL OBSERVATIONS
Dejerine (1914) was the first to construct a map of the
spinal segmental innervation of the bony skeleton. His work
was based on two principles. The first was the observation
that cutaneous (skin) and deep (muscle, tendon, bone, and
periosteum) sensitivity to pressure could, in cases of certain
central and peripheral nervous lesions, be dissociated
because an anesthetized area of skin may overly deeper tis-
sue that was not anesthetized, or vice versa. For example,
a C5 lesion causing cutaneous anesthesia over a bone,
without coincident deep anesthesia beneath the area of
anesthetized skin, indicated to Dejerine that the deep tissue
in that region was not innervated by the C5 spinal segment.
The second was meticulous cadaver dissection of spinal
nerves from their radicular origin. It is important to note
however, that much of the pressure Dejerine applied to
deep structures must have stimulated afferent fibers in
muscle, tendon and ligaments, rather than in periosteum
and bone alone. There are only a few sites in which boneand periosteum are in close apposition to skin without other
structures in between. Furthermore, it is difficult to con-
ceive that such a defined representation of the innervation
territory of single spinal nerves could be achieved by follow-
ing the fibers within a single spinal nerve through a periph-
eral plexus (e.g., lumbosacral plexus), multiple peripheral
nerves, and the very fine branches that innervate bone and
periosteum.
Kellgren (1939) reported a similar map by examining
the distribution of referred pain following injections of hypo-
tonic saline into deep tissues such as ligaments, tendons,
joint capsules, and muscles. When these deep tissues were
injected, the author noted that the pain experienced by
subjects was referred to cutaneous and muscular areas
associated with defined dermatomes or myotomes, andproposed that the innervation of the deep tissue must have
the same spinal segmental origin as the dermatome or
myotome that the pain was referred to. Using this tech-
nique, Kellgren carefully identified the spinal segmental
innervation patterns for deep tissue throughout the whole
body. The similarity between Kellgrens and Dejerines
maps confirms that what Dejerine mapped was most likely
the innervation of muscle, tendon and ligaments, not bone
and periosteum alone. Furthermore, at no stage was the
term sclerotome used in the study of Kellgren, and no claim
was made that this map was representing the segmental
innervation of bone and periosteum, yet some recent
reports quote this work when defining the sclerotomes. A
notable example is the published chiropractic charts of the
sclerotomes (Banner Therapy Products Inc., 2007). The
term sclerotome was not actually defined until later. This
highlights the notion that the use of the term sclerotome
has become somewhat ambiguous. In many cases, it has
been used to imply the spinal segmental innervation ofdeep tissues, including muscle, tendon, joint capsule, and
ligament as well as bone and periosteum, but this is an
incorrect use of the term.
Inman and Saunders (1944) were in fact the first to use
the term sclerotome in the non-embryological sense. They
studied the distribution of referred pain to non-bony tissues
in patients with focal bone lesions and a group of volunteers
that submitted to direct periosteal stimulation (scratching
with a fine needle), and reported a map of the spinal seg-
ments that were known to innervate the areas of referred
pain for each stimulus site, in a manner similar to that of
Kellgren. However, the distribution of referred pain is diffi-
cult to document accurately because it is generally
described as diffuse and dull, and often perceived over a
number of dermatomes or myotomes. In fact, Inman andSaunders acknowledged that: Our knowledge of the pre-
cise segmental innervation of the sclerotomal areas cannot
at the moment be given with any great precision. They
also commented that their aim was to map the extent of
scleratogenous pain, not to produce a segmental map, con-
trary to the opinions of future authors.
There exist a number of confounding issues regarding
the sclerotomes as derived from these early clinical obser-
vations. The first issue is that it is unclear as to how many
points on the bony skeleton were actually sampled in these
studies. It is difficult to imagine how these stimuli could be
applied to the whole skeleton when deep tissues such as
ligaments, tendons, and muscles overly bone at most points
in the skeleton. The second issue is the notion that when
stimuli were applied specifically to skeletal tissues, theywere applied to the periosteum (by pressure or scratching)
and not to the inside of bone. We are now aware that pri-
mary afferent fibers exist within bone (Bjurholm et al.,
1988; Hill and Elde, 1991; Mach et al., 2002), and that
they may be activated with many different stimulus types
(Furusawa, 1970; Seike, 1976). The segmental innervation
of the bone as opposed to the periosteum is yet to be
defined at all. A third point of contention is that most of
these studies were based on mapping the distribution of
referred or deep pain, but because pain of these types is so
dull and diffuse, it is difficult to ascribe the origin of the
pain to a single dermatome or myotome and thus to a sin-
gle spinal segment. Finally, referred pain is most likely an
indication of common segmental spinal cord mechanisms. It
is probable that spinal and supraspinal circuits influencedthe extent of referred pain perceived by subjects in these
studies, confounding the results reported. The accuracy of
the sclerotomes presented in these early studies was there-
fore questionable, and in line with the perceived lack of clin-
ical importance at the time, led to their exclusion in the
literature for many years. It should be emphasized that the
sclerotome maps marketed at present (aimed mainly at
chiropractic use e.g., Banner Therapy Products Inc., 2007)
are based on these early clinical observations. As a result,
they show only vague areas of deep, radiating or referred
pain, and not specific skeletal territories supplied by single
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spinal nerves. A more concise method for mapping the scle-
rotomes would result in a more effective use of the principle
in the clinical setting.
A number of more recent reports of patients with bone
disorders such as melorheostosis (Murray and McCredie,
1979; North and McCredie, 1987) and thalidomide induced
malformations (McCredie, 1977; McCredie et al., 1984;
McCredie and Willert, 1999) have cited the sclerotomes toexplain the pathology they observed. Thalidomide is well-
known for its anti-angiogenic and immuno-modulatory
properties, but was also used as an antiemetic agent to
control nausea in pregnant females in the 1960s (Perri and
Hsu, 2003; Franks et al., 2004). However, babies born to
mothers that had taken thalidomide developed gross
deformities involving skin, muscle, and skeletal structures.
Of the skeletal deformities, reductions of the limbs involving
malformation of the long bones were most obvious
(McCredie, 1977; McCredie et al., 1984; McCredie and
Willert, 1999). McCredie (1974) hypothesized that this was
a result of toxic damage to neural crest cells (the segmen-
tally organized precursors of peripheral sensory neurons).
She predicted that if a segment of neural crest fails to de-
velop, then one would expect the skeletal structures sup-plied by the sensory nerves derived from that segment to
be missing (or at least malformed), possibly because of
impaired neurotrophic influences. McCredie retrospectively
examined the radiographs of limb reductions in thalidomide
babies, and observed that most limb reductions could be
approximated by theoretically subtracting a single sclero-
tome, as mapped by Inman and Saunders (1944), from a
complete appendicular skeleton (McCredie, 1977; McCredie
et al., 1984; McCredie and Willert, 1999). She argued that
the sclerotomes provided a mechanism by which one could
explain the effects of thalidomide poisoning, and therefore
that they must indeed exist. However, there is some debate
as to whether thalidomide affects neural crest cells directly,
or causes secondary neuropathy related to an effect on tar-
get tissues (de Iongh, 1990). In addition, Strecker and Ste-phens (1983) showed that physically blocking the early de-
velopment of peripheral nerves did not result in any limb
reductions at all. DAmato et al. (1994) further showed that
thalidomide is a potent inhibitor of angiogenesis, and
Strecker and coworkers (Stephens et al., 2000; Stephens
and Fillmore, 2000) subsequently suggested that thalido-
mide inhibits the transcription of genes that drive angiogen-
esis. Therefore, it appears that the observed malformations
might result from a lack of blood supply to the developing
limb, not from a direct toxic effect on developing segmental
sensory neurons. This suggests that McCredies hypothesis
regarding the importance of the segmentally organized
neural crest cells in thalidomide teratogenicity may have
been overstated, and raises the possibility that the implied
existence of the sclerotomes may not be real.Melorheostosis is a disease that is characterized by
abnormal longitudinal growth of sclerotic tissue in long
bones. Murray and McCredie (1979) and North and McCre-
die (1987) loosely correlated the distribution of sclerotic tis-
sue in patients with the distribution of single sclerotomes,
as defined by Inman and Saunders (1944). They noted that
in some cases, cutaneous disturbances associated with a
single dermatome of the same segmental origin were also
present, reinforcing the notion that single spinal segments
could be associated with defined skeletal tissue territories.
An important feature of these studies is that melorheostosis
presents in the adult, and thus the pathological distribution
of the sclerotic tissue can be compared with the sclerotome
maps of Inman and Saunders (1944) with more confidence
than thalidomide induced limb reductions. Nonetheless, a
clearer understanding of how segmental innervation pat-
terns of skeletal tissues in both the embryo and the adult
are organized is required to support the hypotheses that
these authors present, and are indeed necessary to rein-force the idea that sclerotomes do exist in a form useful to
such discussion.
EVIDENCE FROM DEVELOPMENTALSTUDIES
The relationship between developing, segmentally
organized sensory and motor neurons in the embryo and
spinal segmental innervation patterns of skin and muscle in
the adult is well documented (Krull, 2001; Wang and Scott,
2002). Primary afferent neurons that innervate skin are
derived from neural crest cells that migrate away from the
developing neural tube and undergo significant proliferation
adjacent to primitive somites. Motorneurons originate in the
basal plate of the developing neural tube and their develop-
ing axons project into the primitive somites. Somites are
organized in a segmental manner, so when the peripheral
processes of neural crest cells, or axons of developing
motorneurons, extend into the adjacent somites they pro-
vide a template for the segmentation of these neurons. The
somites subsequently differentiate into three regions: an
embryological dermatome, embryological myotome, and
embryological sclerotome. The embryological dermatome
develops into axial skin and the embryological myotome
develops into both axial and appendicular muscle tissue, all
of which retain the segmental innervation patterns imposed
by the developing neurons. Skin of the limbs develops from
tissues associated with the outgrowth of the limb bud, so
the peripheral processes of developing neural crest cellshave to extend beyond the somite, and out to the develop-
ing limb bud to innervate their final target tissue. There is
significant evidence that this outgrowth is mediated by
either neurotrophic factors and/or contact guidance mecha-
nisms, and that the segmentation is maintained when the
processes travel over such long distances (Davies and
Lumsden, 1990; Wang and Scott, 2002). Thus, it appears
that the spinal segmental innervation patterns of skin and
muscle of the adult develop in part from patterns imposed
by somites during embryonic development.
If the embryonic development of the innervation of skel-
etal structures follows the same principles that exist for
skin and muscle, then it would seem reasonable to presume
that developing neurons in the embryo might also impose
segmental innervation patterns on the adult skeleton (andmanifest as sclerotomes). In the development of the axial
skeleton, neural crest cells extend peripheral processes into
the surrounding embryological sclerotome, forming the ba-
sis for segmental innervation of the axial skeleton, including
the vertebra and ribs. However, this is somewhat compli-
cated because each embryological sclerotome is split: its
cranial part forms the caudal part of the vertebra above,
and its caudal part forms the cranial part of the vertebra
below (Balling et al., 1992). This implies that in the adult, a
single spinal segmental nerve should innervate two adja-
cent vertebrae. This is not acknowledged in the maps of
958 Ivanusic
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Dejerine (1914). Furthermore, Kellgren (1939) and Inman
and Saunders (1944) did not document segmental innerva-
tion patterns for axial tissues at all, and therefore offer no
clarification on the matter. The case for the appendicular
skeleton is also unclear. Peripheral processes of neural crest
cells extend into the mesenchyme of the limb bud
(Cameron and McCredie, 1982) which subsequently forms
the bones of the developing limb (Olsen et al., 2000). How-ever, the extent to which the developing primary afferent
fibers maintain segmental innervation patterns in develop-
ing limb bones is yet to be determined. Until these issues
are resolved, some caution should be practiced before pre-
suming that the development of segmentally organized
nerves in the embryo imposes a segmental innervation pat-
tern on adult skeletal tissues, as it appears to for cutaneous
and muscular tissue. The evidence to imply that this might
form the basis of the sclerotomes does not as yet exist.
ANATOMICAL AND PHYSIOLOGICALINVESTIGATIONS IN ANIMAL STUDIES
It is relatively easy to study the connections between a
single spinal nerve and either skin or muscle in animal stud-
ies. Connectivity has been established with electrophysio-
logical recordings of spinal nerve activity evoked by stimu-
lation of skin or muscle (Dykes and Terzis, 1981), muscle
activity evoked by electrical stimulation of single spinal
nerves (Browne, 1950; Thage, 1965), application of neuro-
anatomical tracers to skin and muscle (Takahashi et al.,
2003), and by dye extravasation following electrical stimu-
lation of single spinal nerves (Takahashi and Nakajima,
1996). Using these techniques, it has been possible to
define territories innervated by single spinal nerves and
then reconstruct a concise map representing the innerva-
tion patterns of many spinal nerves in skin and muscle.
Maps of dermatomes and myotomes produced in this way
are very similar to maps produced from clinical (and experi-mental) observations in human studies (Warwick et al.,
1989; Greenberg, 2003), and have provided empirical evi-
dence that spinal segmental innervation patterns do indeed
exist for skin and muscle. However, examining the connec-
tivity between the bony skeleton and spinal nerves is diffi-
cult, because bone is a very hard, mineralized tissue that is
difficult to work with. Most of the techniques applied to
establishing dermatomes and myotomes are not appropri-
ate for the determination of sclerotomes. A single study has
attempted to address the issue of the segmental innerva-
tion of bony tissue using anatomical techniques. Gajda
et al. (2004) placed a retrograde tracer (DiI) under the per-
iosteum of the rat tibia, which is easy to expose because of
its close proximity to the skin, and reported labeled neuro-
nal cell bodies in the dorsal root ganglia confined predomi-nantly to spinal cord levels L3 and L4. The author of the
present paper has observed similar results following injec-
tions of another retrograde tracer (Fast Blue) into either
the medullary cavity or epiphyses, in addition to the perios-
teum, of the rat tibia (Ivanusic, unpublished observations).
However, using this approach, it would be very difficult and
time consuming to place the tracer into enough points in
the skeleton to be able to reconstruct the whole sclerotomal
map. No other anatomical or physiological studies of con-
nectivity between single spinal nerves (or spinal cord seg-
ments) and bone could be found in the literature. It is clear
that anatomical and physiological techniques need to be
exploited further to study the sclerotomes. In particular,
empirical mapping of connectivity between single spinal
segmental nerves and bony tissues, as has been done for
skin and muscle, is required to confirm the existence of the
sclerotomes.
CONCLUDING REMARKS
The sclerotomes are used by clinicians in many health-
care settings to aid in the diagnosis and description of a va-
riety of deep and/or skeletal tissue pathologies and pain
syndromes. However, we are currently relying on early clin-
ical or experimental observations of referred mechanisms of
deep pain to approximate the sclerotomes. The maps
reported in the early literature are not complete, and they
should be interpreted with consideration of limits in the
techniques used. They show only vague areas of deep, radi-
ating or referred pain, and not specific skeletal territories
supplied by single spinal nerves. Further to this, a definitive
description of the sclerotomes in the adult is complicated by
the lack of knowledge regarding the development of skele-
tal innervation in the embryo. We do not have the evidence
to imply that the development of segmentally organized
nerves imposes a segmental innervation pattern on skeletal
tissues, as it appears to for cutaneous and muscular tissue.
Finally, there is little evidence based on anatomical and
physiological studies of the sort have been instrumental in
confirming the existence of segmental innervation patterns
in skin and muscle. Thus there appears to be little direct
evidence for the existence of the sclerotomes. It is pro-
posed that the nature of the segmental innervation of bony
tissue requires further attention. In particular, more detail
of the anatomical and physiological connections between
single spinal nerves and bone is required. Like the derma-
tomes and myotomes presented in many of the textbooks
today, this will reflect the true patterns of segmental inner-
vation of skeletal tissue in the adult, and provide a defini-tive basis upon which discussions of the sclerotomes can be
based in the future.
ACKNOWLEDGMENTS
The author thanks Dr. Pascal Carrive and Dr. Marius
Fahrer for their assistance in the translation of Dejerines
monograph (Dejerine, 1914).
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