Nerves have a structure of considerable complexity with features of special

relevance to nerve injury and nerve regeneration. These include variations

in the cross-sectional areas devoted to fascicular and epineurial tissue, the
fascicular redistribution and mixing of different branch fibers brought about
by fascicular plexuses, and the numbers of nerve fibers representing indi-
vidual branches. The elasticity and tensile strength of nerve trunks and their
capacity to resist traction deformation reside in the fascicular tissue, while
the epineurium provides a protective cushion against compression. The mi-
crostructure of nerve trunks provides the basis for a classification of nerve
injuries into five degrees of severity with partial and mixed types-each
with a clearly defined pathology and distinguishing clinical features. Follow-
ing a transection injury, changes occur in the severed axons, endoneurial
tubes, fasciculi, and nerve trunk. The type of injury and the nature of these
changes determine the outcome of axon regeneration.
Key words: nerve injury nerve regeneration.
MUSCLE & NERVE 13:771-784 1990

THE ANATOMY AND PHYSIOLOGY

OF NERVE INJURY
SIR SYDNEY SUNDERLAND, MD, DSc, FRACS, FRACP

Although it is true that many of the problems of
nerve injury and nerve repair must wait on the
molecular biologist for their solution, it is equally
clear that, for the time being, we cannot afford to
overlook the use of somewhat old fashioned but
well-tried methods and techniques that still have
much to offer. It is such an approach that forms
the substance of this article.
THE MICROSTRUCTURE OF NERVE TRUNKS
A convenient starting point for our purposes is a
transverse section of a peripheral nerve trunk.
This reveals those structural features that have
special relevance to nerve injury (Fig 1). Such a
section shows that nerve fibers are collected into
fasciculi, each fasciculus being (1) surrounded by a
thin but distinctive lamellated sheath of perineu-
rial cells interspersed with fine collagen fibers, and
(2) occupied by a framework of endoneurial tissue
From the Department of Anatomy, University of Melbourne, Australia. Dr.
Sunderland is Professor Emeritus of Experimental Neurology.
Second Annual Reiner Memorial Lecture presented at AAEE (now AAEM)
Annual Meeting, International Symposium on Peripheral Nerve Regener-
ation, Washington, DC, September 17, 1989.
Address reprint requests to Dr. Sunderland at the Department of Anat-
omy, University of Melbourne, Parkville, Victoria, 3052, Australia.
Accepted for publication December 13, 1989
CCC 0148-639W90/090771-014 $04.00
Q 1990 John Wiley & Sons,Inc.
that is organized around each nerve fiber to form
its outer endoneurial sheath.
T h e endoneurial tissue has some tensile
strength. T h e main component giving tensile
strength and elasticity to the nerve, however, is
the perineurium. This sheath also constitutes a
diffusion barrier and resists and maintains an in-
trafascicular pressure. The term perineural is of-
ten used incorrectly to apply to the perineurium.
Perineural means around the nerve trunk and
perineurial means around a fasciculus; the two
terms are not interchangeable.
The fasciculi are, in turn, set in an areolar con-
nective tissue packing, the epineurium, which pro-
tects them from compression. The superficial
epineurium forms an external sheath for the
nerve, which gives it a cord-like appearance and
consistency and which permits it to be easily sepa-
rated from the surrounding tissues.
The deep fascia1 or paraneural tissue refers to
the unnamed, nonspecialized loose meshwork of
areolar connective tissue that fills the space be-
tween specialized structures, such as muscles,
nerves, and vessels, connecting them loosely to-
gether and permitting the movement of one on
the other. Though this tissue is associated in this
way with nerve trunks, it is not regarded as a com-
ponent of the nerve trunk whose outer limits are
clearly outlined by a definitive sheath of epineu-
rial tissue.
T o inspection and palpation, the nerve is a

Anatomy and Physiology of Nerve Injury MUSCLE & NERVE September 1990 771
FIGURE 1. Diagrammatic representation of a transverse section
of a nerve trunk. (From Sunderland S: Nerves and Nerve Inju-
ries. Edinburgh, Churchill Livingston, 1979. Used with permis-
sion.)

cord-like structure; the light microscope examina-

tion of a single transverse section reveals the struc-
tural features just outlined, while the electron mi-
croscope reveals details of only a fragment of the
nerve at very high magnifications. All miss the sig-
nificant point that the structure of a nerve is con-
stantly changing along its entire length because
the fasciculi are repeatedly dividing and uniting to
form complex fascicular plexuses (Fig. 2). No fas-
ciculus runs an independent unaltered course
along the entire length of a nerve. FIGURE 2. Fascicular plexus formations in a 3 cm length of the
The examination of successive transverse sec- musculocutaneous nerve reconstructed from a serially sectioned
tions reveals that these plexus formations are re- specimen. (From Sunderland S: Nerves and Nerve Injuries. Ed-
sponsible for bringing about: inburgh, Churchill Livingston, 1979. Used with permission.)

1. Repeated changes in the size, number, and ar-

rangement of the fasciculi so that sections
taken more than a few millimetres apart fail to
present fascicular patterns that are identical in
every respect (Figs. 3 and 4).
2. The fascicular redistribution, dispersal, and in-
termingling of different branch fiber systems as
they are traced along the nerve (Fig. 5). Fea- b.
tures of this fascicular behavior are:
a. The number of fasciculi varies from 1 to
more than 100 depending on the nerve and
the level. The following give some idea of c.
the range of variation of fascicular numbers
in 4 specimens of each nerve: d.
Median: 3-22, 5- 16, 4- 13, 15-36.
Ulnar: 1-8, 1-18, 3-8, 12-36. e.
Radial: 1-20, 2- 13, 2-36, 8-29.
Sciatic nerve:
medial popliteal: 11-27, 16-33, 28-93,
32-83.
lateral popliteal: 1-15, 1-21, 5-20, 8-
24.
Generalizing, the fasciculi in the median
and ulnar nerves are larger and fewer in
number above the elbow compared with the
forearm.
T h e size and number of fasciculi are in-
versely related at any level.
T h e fasciculi are smaller and more numer-
ous where a nerve crosses a joint.
For a given total fascicular area, the tensile

772 Anatomy and Physiology of Nerve Injury MUSCLE & NERVE September 1990

Supracondylar E picondyle
FIGURE 3. Variations in the size and number of fasciculi in a
specimen of the radial nerve. (From Sunderland S: Nerves and
Nerve Injuries. Edinburgh, Churchill Livingston, 1979. Used with
permission.)
strength of a nerve increases with the num-
ber of fasciculi. Cables of the same size are
stronger and more flexible if composed of
many strands.
The Cross-Sectional Areas of Nerves Devoted to
Fascicular and Epineurial Tissue. The relative
amounts of fascicular and epineurial tissue con-
@@
A f- 2mm+ B A on 6
FIGURE 4. The fascicular patterns present in transverse sec-
tions from a radial nerve taken 2 mm apart. (From Sunderland S:
Nerves and Nerve Injuries. Edinburgh, Churchill Livingston,
1979. Used with permission.)
Anatomy and Physiology of Nerve Injury
FIGURE 5. Diagrammatic representation of the fascicular redis-
tribution of nerve fibers brought about by the fascicular plexus.
(From Sunderland S: Nerves and Nerve Injuries. Edinburgh,
Churchill Livingston, 1979. Used with permission.)
tributing to the cross-sectional area of the nerve
varies from level to level along the same nerve. In
general, the fascicular contribution varies from
about 30% to 70%. The sciatic nerve in the gluteal
region is an exception in that the fascicular tissue
in most of these nerves occupies only 20% to 30%
of the nerve; in one specimen examined, this area
was as low as 12%.
As we shall see, the connective tissue compo-
nent of a nerve trunk and features of the fascicu-
lar anatomy of nerves provide an important line
of defense against compression injury.
The Fascicular Redistribution, Dispersal, and Mixing
of the Different Branch Fiber Systems. Fascicular
plexuses bring about the fascicular redistribution,
dispersal, and intermingling of different branch
fiber systems as they are traced along the nerve
(Fig. 6). Thus the arrangement, considered from
distal to proximal, is one-in which the localization
of any particular branch system is at first discrete,
then discrete in combination with other branch fi-
ber% and finally a predominant one only until fi-
ber scattering ultimately reaches a degree at the
MUSCLE & NERVE September 1990 773
 13 mm

63mm 85mm 127mm i8omm

FIGURE 6. The fascicular redistribution of branch fiber systems in a radial nerve affected by fascicular plexus formations. The figures
give the level of the section in mm above the lateral humeral epicondyle. APL and M indicate anterior, posterior, lateral, and medial
aspects of the nerve. o superficial radial; 0 combined posterior interosseous fibers, S, supinator; + extensor carpi radialis brevis; x
extensor carpi radialis longus; * combined radial extensor fibers; A brachioradialis; A brachialis. (From Sunderland S: Nerves and
Nerve lnjuries. Edinburgh, Churchill Livingston, 1979. Used with permission.)

root of the limb where there is no segregation or
localization of the branch fiber system.
Expressed in another way, this means that, at
the root, the nerve fibers representing the distal
branches are intermingled and widely distributed
through the fasciculi of the nerve. On the other
hand, the fibers of proximal branches are concen-
trated in that sector of the nerve from which
branching is about to occur, though the fibers will
be mixed with those for distally destined branches.
As the nerve proceeds distally, the fascicular plex-
uses effect a sorting out of the different branch
fiber systems until, finally, the fibers for a particu-
lar branch are collected into their own fasciculus,
or group of fasciculi, which then leaves the nerve
as a definitive branch.
The fascicular composition of the fibers repre-
senting any particular branch can be expressed in
terms of three levels:
1. At the root of the limb, the fibers of branches
at and below the elbow and knee are widely dis-
tributed over many, if not all, of the fasciculi.
They are mixed with the fibers of other more
distal branches in varying combinations and
proportions, though each fasciculus does not
necessarily contain fibers from every branch.
T h e fibers of high branches, though mixed
with those from distal sources, are relatively lo-
calized and superficially placed because they
are shortly to leave the nerve.
2 An intermediate zone where the fibers of a par-
ticular branch are contained in fasciculi that,
though not devoted exclusively to them, occupy
a relatively localized position in the nerve.
3. A distal zone where,-for a variable, but usually
short, distance above the site of branching, the
fibers of a branch are contained in a fasciculus
or group of fasciculi devoted exclusively to

774 Anatomy and Physiology of Nerve Injury MUSCLE & NERVE September 1990
 them, and are sharply localized and superfi-
cially placed in the nerve (Fig. 7).
Fasciculi are of two types as regards their branch
fiber composition: (1) Simple fasciculi that are
composed of fibers from the same source, and (2)
compound fasciculi that are composed of fibers
from several different sources in varying num-
bers, combinations, and proportions.
Numbers of Nerve Fibers Representing Dlfferent
Branches. Counting the number of fibers in ev-
ery branch of a major peripheral nerve would be a
formidable task. It is possible to obtain some esti-
mate of this feature, however, by measuring the
cross-sectional area of the fasciculi devoted solely
to individual branches. Admittedly, this method
has its limitations because the relationship be-
tween area and numbers is affected by such fac-
tors as the size of individual nerve fibers and the
amount of intra-fascicular endoneurial tissue.
With this proviso, the cross-sectional area of the
fasciculi devoted to individual branches may be ac-
cepted as a rough estimate of the number of fibers
in a nerve representing individual branches. Such
data is available for the major peripheral nerves.
As an example, the percentage values for the
branches of the radial nerve, averaged from the
examination of 11 specimens, are:
Superficial radial 29
Brachialis 2
Brachioradialis 6
Extensor carpi radialis longus 9
Extensor carpi radialis brevis 7
Posterior interosseous 47
In expressing branch fiber numbers in this way, it
should be noted that such estimates are also influ-
enced by variations in the number of branches,
the level of branching, and the distribution of
those branches.
The percentage cross-sectional area of fascic-
uli composed of fibers representing individual
branches also depends on the level at which the
measurement is made. This is illustrated by refer-
ence to the percentage cross-sectional fascicular
areas of a median and an ulnar nerve trunk occu-
pied by cutaneous and “muscle” nerve fibers from

L v
FIGURE 7. Transverse sections from a median nerve above the elbow and at the wrist to illustrate the sorting out of the different branch
fiber systems that occur between these levels. (A) In the section above the elbow, the circles represent groups of fasciculi in which
different branch fibers are represented. Al, anterior interosseous; FCR, flexor carpi radialis; FDS, flexor digitorum sublimis; PC, palmar
cutaneous; PT, pronator teres; T, fibers of terminal branches in the hand. (B)In the section at the wrist, the circles represent individual
fasciculi. A.B.C., digital cutaneous fibers from the third, second, and first interspaces; D, cutaneous fibers from the radial side of the
thumb; M, fibers to thenar muscles; L, lumbrical fibers. (From Sunderland S: Nerves and Nerve Injuries. Edinburgh, Churchill Livingston,
1979. Used with permission.)

Anatomy and Physiology of Nerve injury MUSCLE 8, NERVE September 1990 775
the hand, measured at the wrist and above the el-
bow :
Wrist / Elbow Muscle Cutaneous
Median nerve 614 94 I 6 6
Ulnar nerve 44 I 28 56 I 3 5
Above the elbow, the same nerve fibers from the
hand are now combined with fibers of the remain-
ing branches of the nerve so that the former now
occupy a reduced percentage cross-sectional fas-
cicular area of the nerve. T h e significance of this
feature will emerge as we proceed.

The Blood Supply of Nerves. Regarding this fea-

J J
ture of peripheral
- - nerves, there is time only for a
passing reference to points that call for special
emphasis.

1. Nerves are well supplied by a longitudinally ar-

ranged anastomosing system of nutrient vessels
and networks on the surface and within the
nerve. This system is served by a succession of
regional nutrient arteries that enter a nerve
along its course. The arrangement is one that
ensures a continuing supply of blood to the
nerve should one or more entering nutrient ar-
teries be blocked or destroyed.
2. The largest nutrient vessels are located on the
surface of the nerve and in the epineurium.
3. The largest vessels inside a fasciculus are capil- J 4 4 J
laries. FIGURE 8. Changes occurring in the various components of a
4. There is much experimental and clinical evi- nerve trunk as it is stretched to structural failure. Only one fas-
dence to the effect that the blood supply to pe- ciculus in the nerve is represented. (From Sunderland S: Nerves
ripheral nerves plays a critical role in the sur- and Nerve Injuries. Edinburgh, Churchill Livingston, 1979. Used
vival and functional integrity of axons. with permission.)

THE TENSILE STRENGTH AND ELASTICITY
OF NERVE TRUNKS
A nerve trunk runs an undulating course in its
bed, the fasciculi run an undulating course in the
epineurium, and the nerve fibers run an undulat-
ing course inside the fasciculi. This means that the
length of a nerve trunk, and its contained nerve
fibers between any two fixed points on the limb, is
greater than a straight line joining those points.
When a nerve is gradually stretched, the undu-
lations in the nerve and the fasciculi are first eIim-
inated but not those of the nerve fibers, which re-
main tension free inside the fasciculi (Fig. 8). In
this way, the slack provided in the system absorbs
and neutralizes traction forces generated during
limb movements so that the contained nerve fibers
are at all times protected from being over-
stretched.
When the nerve and its contained fasciculi are
finally straightened, the tensile properties of the
nerve are recruited and the system commences to
resist further elongation and to behave as an elas-
tic material. With continued stretching, the nerve
fibers are first straightened, then stretched, and fi-
nally ruptured. The nerve, however, continues to
behave as an elastic structure despite the fact that
nerve fibers have ruptured inside the fasciculi. Fi-
nally, the perineurial tissue ruptures, and with this
structural failure the nerve loses its tensile
strength and elasticity.
Points of particular interest in this sequence of
events include:

776 Anatomy and Physiology of Nerve Injury MUSCLE & NERVE September 1990
 ~

Table 1. Percentage elongation of human nerve trunks under tensile loading rate of elongation
7.5 cmlrnin

At the elastic limit At mechanical failure

Nerve Range Mean Ranae Mean
-~
Ulnar 8 to 21 15 9 to 26 18
Median 6 to 22 14 7 to 30 19
Medial popliteal 7 to 21 17 8 to 32 23
Lateral popliteal 9 to 22 15 10 to 32 20
Anterior spinal roots 9 to 15 11 9 to 21 15
Posterior spinal roots 8 to 16 12 8 to 28 19

1. The range of elongation over which a nerve re-
tains its elasticity depends on such factors as
the magnitude of the deforming force, the rate
of its application and the time for which it op-
erates, and its fascicular structure. Stretching
the nerve at '7.5 cms/min gives a range of elas-
ticity of 6% to 20% of the length of nerve being
stretched (see Table 1).
2. The rupture of nerve fibers precedes structural
failure of the fasciculi and occurs with elonga-
tions of about 4% after the slack in the nerve
has been taken up and it commences to take
load.
3. A nerve retains its elastic properties as long as
the perineurium remains intact.
4. As the fasciculi are stretched, their cross-
sectional area is reduced, the intrafascicular
pressure is increased, nerve fibers are com-
pressed, and the intrafascicular microcircula-
tion is compromised.
5. With tensile loading, the rate of deformation is
as important as the magnitude of the deform-
ing force.
6. Traction forces generated during normal limb
movements are unlikely to reach limits that
would compromise nerve fibers inside the fas-
ciculi.
THE CUSHlONlNa ROLE OF THE EPINEURIUM
1. A special feature of peripheral nerves is the of-
ten large amount of epineurial connective tis-
sue that separates the fasciculi and holds them
together.
2. When pressure is applied to a nerve, the
epineurium functions as a shock-absorber
which dissipates the stresses set up in the nerve,
thereby cushioning the fasciculi and their con-
tained nerve fibers and in this way protecting
them from damage.
3. Where are Of large and
closely packed fasciculi with little supporting
epineurial tissue, they are more vulnerable to
mechanical injury than where the fasciculi are
smaller and more widely separated by a greater
amount of epineurial tissue. With the former
arrangement, forces fall maximally on the main
component of the nerve trunk which is fascicu-
lar tissue and, therefore, nerve fibers. In the
latter, the damaging forces would be dissipated
and cushioned by the epineurial tissue packing
and the fasciculi would be more easily dis-
placed within the nerve and so would tend to
escape (Fig. 9).
The significance of this feature is illustrated by
reference to the well-established clinical finding
that, in injuries of the sciatic nerve, the common
peroneal division is known to be more frequently
injured and more often suffers greater damage
than the tibial.
An investigation of the cross-sectional area of
the sciatic nerve and its common peroneal and tib-
ial divisions devoted to fasciculi and to epineurial
tissue has revealed that the fascicular pattern of
the common peroneal does present features that
i
FIGURE 9. Dispersion of compression stresses by the epineurial
tissue. (From Sunderland S: Nerves and Nerve Injuries. Edin-
burgh, Churchill Livingston, 1979. Used with permission.)

Anatomy and Physiology of Nerve Injury MUSCLE & NERVE September 1990 777
render this nerve more susceptible to injury than
the associated tibial division. T h e peroneal divi-
sion, particularly in the distal half of the thigh, is
composed of fewer and larger fasciculi with less
epineurial tissue than is the corresponding tibial
division (Fig. 10). This morphologic difference is a
significant factor contributing to the increased sus-
ceptibility of the common peroneal nerve to
stretch and compression injury. In addition, the
common peroneal division usually contains much
less adipose tissue in the epineurium than does
the tibial.
THE STRUCTURE OF NERVE ROOTS
It is worth noting that nerve roots are more vul-
nerable to traction and compression injury than
nerve trunks because (1) they lack both epineurial
and perineurial tissue components (Fig. 1); (2)
nerve root fibers are arranged in parallel nonplexi-
form bundles; and (3) the collagen fibers of the
endoneurium are fewer and finer than elsewhere.
A CLASSIFICATION OF NERVE INJURY
Currently, there are two classifications of nerve in-
jury based not on the cause but on the nature of
the lesion. In Seddon's classification, the terms
neurapraxia, axonotmesis, and neurotmesis were
introduced to cover conduction block, loss of con-
tinuity of axons, and loss of nerve trunk continu-
ity. The second, which I naturally prefer since it is
my own, is based on the histologic structure of a
nerve trunk previously outlined. It recognizes five
degrees or types of nerve damage of increasing se-
verity from conduction block followed successively
by loss of continuity of axons, then of nerve fibers,
the fasciculi, and finally the entire nerve trunk
(Fig. 11). Since my brief is to adhere strictly to the
role of anatomy in these matters, reference to clin-
ical detail is omitted.
First Degree Injury (lo). This is the temporary
conduction block lesion in which axonal continuity
is preserved. The nerve conducts as far as and be-
low the block, but not across it.
Continuity of the endo-
Second Degree Injury ( 2 O ) .
neurial sheath of nerve fibers is preserved. Walle-
rian degeneration occurs below the lesion, how-
ever, so that axonal continuity with the periphery
is lost. Later the length of the axon that has per-
ished as the result of the injury will be replaced by
regeneration. Importantly, each regenerating
axon as it grows is confined to the endoneurial
tube that originally contained it. This ensures that
778 Anatomy and Physiology of Nerve Injury
28
Sciatic notch
Junction upper f a
of thigh
Mid thigh
Joint lml
a&O&~c$)o Neck of the f~bula
@
37
FIGURE 10. Diagrammatic representation of the fascicular struc-
tures of a sciatic nerve and its common peroneal and tibial divi-
sions at the levels indicated. The figures give the cross-sectional
fascicular areas measured at those levels. (From Sunderland S:
NeNeS and Nerve injuries. Edinburgh, Churchill Livingston,
1979. Used with permission.)
each axon is inevitably directed back to the end
organ that it originally innervated. Consequently,
the restored pattern of innervation is identical
with the original and function is fully restored.
Third Degree Injury (3"). This is the concealed in-
trafascicular lesion in which the fasciculi are left in
continuity but continuity of nerve fibers is lost.
The damage may be localized o r be irregularly
distributed along a considerable length of the
nerve.
The internal structure of the fasciculi is disor-
ganized with (1) the disintegration of axons and
wallerian degeneration; (2) the loss of continuity
of the endoneurial sheath and, therefore, the en-
tire nerve fiber; and (3) hemorrhage, edema, an
inflammatory reaction, and finally fibrosis.
Axon regeneration is now complicated in two
ways:
1. Intrafascicular fibrosis blocks some axons, de-
lays others in their growth, diverts others from
MUSCLE & NERVE September 1990
FIGURE 11. Diagrammatic representation of five degrees of nerve injury. (From Sunderland S: Nerves and Nerve Injuries. Edinburgh,
Churchill Livingston, 1979. Used with permission.)
their proper course and, later, by constricting
those that are successful in negotiating the scar
tissue between the nerve fiber ends, adversely
affects their subsequent growth, development,
and function. This disorderly axon growth may
be so pronounced that the involved fasciculi
develop a fusiform swelling at this site.
2. Loss of continuity of the nerve fibers means
that regenerating axons, though still confined
within the fasciculi, are no longer confined to
the endoneurial tubes that originally contained
them. Since there is no known mechanism di-
recting axons into their original or functionally
related endoneurial tubes, many fail to do so
and instead are misdirected into foreign ones.
The significance of the erroneous cross-shunting
of axons occurring in this way depends on the fi-
Anatomy and Physiology of Nerve Injury
ber composition of the fasciculi (Fig. 6). Where
the fibers have the same or a functionally related
destination, the consequences are minimal. Where
the fiber composition is one in which sensory and
motor fibers and those representing functionally
unrelated systems are intermingled, however, the
consequences of the erroneous entry of axons into
foreign tubes can be serious. Despite the fact that
the nerve trunk is left in continuity, recovery fol-
lowing severe third degree damage is often negli-
gible.
Fourth Degree InJury (4'). In this type of injury,
the fascicular structure of the nerve has been de-
stroyed, nerve trunk continuity being preserved
by a strand of disorganised tissue. Regenerating
axons are now free to escape not only from endo-
neurial tubes but also from fasciculi. The trauma-
MUSCLE & NERVE September 1990 779
tized, disorganized segment of the nerve trunk is
replaced by a barrier of fibrous tissue in which
axon growth is arrested. This is the type of injury
that requires excision of the damaged segment
and some form of nerve repair.
Flfth Degree Injury (5'). This represents loss of
continuity of the nerve trunk. Though the clinical
details of this classification are not the concern of
this presentation, one can say that the classifica-
tion is one that (1) has a sound pathologic basis;
(2) relates to the clinical events associated with a
lesion; (3) has diagnostic, prognostic and thera-
peutic significance; (4)involves a terminology that
is readily understood, and (5) has the added at-
tractiveness of simplicity.
Mixed Nerve Injury. These are lesions in continu-
ity in which all nerve fibers are damaged but to a
varying degree.
Partial Nerve Injury. These are lesions in which
some nerve fibers escape while others sustain
damage of varying degree. A common lesion in
this category is partial severance of the nerve
trunk. The consequences of such an injury de-
pend on (1) the size and number of the fasciculi
composing the nerve at that level; and (2) the
branch fiber composition of the affected fasciculi.
Size and Number of the Farciculi (Figure 12).
Where the fasciculi are small, numerous, and well
separated by epineurial tissue, such lesions tend to
be self-limiting. When the fibers are contained in
one or two large fasciculi, however, breaching
these fasciculi has serious consequences.
The Branch Fiber Composition of the Severed Fa$-
ciculi (Figure 13). Partial lesions produce variable
FIGURE 12. The effect of fascicular structure on the conse-
quences of a partial nerve injury. (From Sunderland S: Nerves
and Nerve Injuries. Edinburgh, Churchill Livingston, 1979. Used
with permission.)
780 Anatomy and Physiology of Nerve Injury
30
154 mm
FIGURE 13. The effect of the branch fiber composition of injured
fasciculi in a partial nerve injury. The notations are given in Fig-
ure 6. (From Sunderland S : Nerves and Nerve Injuries. Edin-
burgh, Churchill Livingston, 1979. Used with permission.)
effects at the periphery depending on the branch
fiber composition of the affected fasciculi that is,
in turn, determined by the level of the injury.
Where the severed fasciculi contain a few of the fi-
bers of some or all branches, the resultant loss of
function is minimal and widespread and might
even escape detection clinically. On the other
hand, where the severed fasciculi contain all or
the majority of the fibers of a particular branch,
the peripheral effects are sharply localized and
clinically obvious. Thus, a partial injury at one
level may either escape detection or give a widely
distributed paresis, but a corresponding lesion at
another level or involving a different sector of the
nerve may produce a sharply localized paralysis or
sensory loss.
THE EFFECT OF A TRANSECTION INJURY
ON THE NERVE BELOW THE LESION
Following a transection injury, changes occur in
the axons and myelin, the endoneurial tubes, the
fasciculi, and the nerve trunk.
The Axon8 and Myelin. The final stage of walle-
rian degeneration is one in which the interior of
the nerve fiber is occupied by axon and myelin de-
bris which is removed by the phagocytic activity of
macrophages and Schwann cells.
The Endoneurial Tubes. With the removal of the
axon and myelin debris, tension is reduced in the
endoneurial wall of the fiber which slowly contracts
down on the remaining contents of the tube, which
are Schwann cells, so that its caliber is gradually re-
duced. This reduction increases with the duration
MUSCLE & NERVE September 1990
of denervation, rapidly over the first 3 months be-
yond which there is little further change.
The fibers are affected in proportion to their
size, so that the largest are ultimately reduced to
tubes 2 to 3 pm in diameter. At the end of 3
months, most tubes are less than 3 pm in diameter
with only an occasional tube of 4 p,m (Fig. 14).
The Fasciculi. The shrinkage of the endoneurial
tubes is associated with a corresponding atrophy
of the fasciculi. Thus, the cross-sectional fascicular
area is reduced by about 50% to 60% at 2 months,
and then by about another 10% over the next
month, beyond which there is no further signifi-
cant reduction (Table 2).
The Nerve Trunk. The epineurial tissue under-
goes little change except for some edematous
swelling at the nerve end. This tissue is excised at
the time of the repair.
Because the fasciculi and epineurial tissue re-
act so differently to denervation, it follows that the
extent of the shrinkage of the nerve trunk will be
influenced, not only by the duration of denerva-
tion, but also by the percentage cross-sectional
area of the nerve occupied by fascicular tissue.
Thus, the reduction will be greater when the fas-
ciculi are closely packed and occupy most of the
cross-sectional area of the nerve than where the
fasciculi are small and widely separated by a large
amount of epineurial tissue.

1234567890 123456789012345 123456789012345 12345

Diameter of endoneuriol tubes (microns)

FIGURE 14. Histograms of endoneurial tube shrinkage with increasing periods of denervation (Aus-
tralian marsupial, Trichosurus vulpecula). (From Sunderland S: Nerves and Nerve lnjuries. Edin-
burgh, Churchill Livingston, 1979. Used with permission.)

Anatomy and Physiology of Nerve Injury MUSCLE & NERVE September 1990 781
 Table 2. Nerve trunk and fascicular atrophy consequent
Axon Regeneration and Functional Recovery. At
on denervation. the outset it is necessary to emphasise the impor-
tance of carefully distinguishing between axon re-
Duration of Percentage Percentage
generation and the functional outcome of that re-
denervation fascicular nerve trunk
Nerve in days atrophy atrophy generation. The recovery of function requires far
more than the regeneration of axons to replace
Ulnar 44 64 49 the part lost below the injury. Of even more im-
Median 49 54 10
portance is the final destination of those axons be-
Ulnar 59 67 28
Median 59 50 31 cause, for regeneration to be functionally effec-
Ulnar 68 61 56 tive, each axon must reach and reinnervate its old,
Ulnar 76 50 59 or at least a functionally related, end organ. Fail-
Ulnar 89 68 35 ure to do this represents abortive and wasteful re-
Median 89 56 43
generation, which leaves recovery incomplete and
Ulnar 140 61 30
Median 140 68 26 impaired.
Median 185 62 25 Thus, axon regeneration per se does not nec-
Ulnar 196 54 45 essarily guarantee functional recovery and, be-
Ulnar 224 63 54 cause it is possible to have good axon regeneration
Median 224 54 45
33
and yet little functional recovery, it is necessary at
Median 229 59
Ulnar 229 69 54 all times to keep in mind that axon regeneration
Median 252 68 42 and functionally effective axon regeneration are
Ulnar 254 62 53 two very different events in the regenerative pro-
Ulnar 254 67 52 cess.
Ulnar 280 74 55
Ulnar 335 72 22
Ulnar 335 74 42 Neurotropism. It is now well established that,
Ulnar 444 88 86 when the nerve ends are well separated, regener-
Ulnar 444 67 61 ating axons are attracted to the distal nerve stump
Ulnar 485 72 48 under the influence of neurotropic factors elabo-
Ulnar 485 66 56
~
rated in and operating from that site. The source
Because of dffferencesin the cross-sectional areas of the distal nerve of the neurotropic factor appears to be widely dis-
end devoted to fascicularand epfneurfaltissue, the degree of nerve tributed throughout the tissues of the distal stump
trunk and fasocular atrophy do not necessanly correspond (Australfan
marsupal. Trrchosurus vulpecula) and is not confined to Schwann cells as was origi-
nally believed.
This influence, however, becomes irrelevant
Consequently, the reduction in the cross- after nerve suture because when regenerating ax-
sectional area of the nerve below the transection ons emerge from the proximal stump they are al-
does not follow the fascicular atrophy. On the ready at the distal nerve end. The question at is-
contrary it will, for a given period of denerva- sue now becomes one that asks, are there
tion, vary irregularly depending on fascicular- neurotropic influences operating at the suture line
epineurial tissue ratios. This is illustrated in Ta- interface that impart a matching specificity to the
ble 2. process whereby each regenerating axon is inevi-
tably attracted back to the endoneurial tube that it
THE MANNER IN WHICH ANATOMICAL FEATURES originally occupied or to which it is at least func-
AT THE SUTURE LINE INFLUENCE THE OUTCOME tionally related. It would be reassuring to know
OF AXON REGENERATION that such influences do exist but, unfortunately,
The concluding section of this saga on the anat- there is some hard evidence against the concept.
omy and physiology of nerve injury concerns
axon regeneration and the inevitable loss of re- 1. Regenerating axons show no preference for
generating axons that occurs as they cross the su- fascicular tissue. They will grow just as readily
ture line. outside the nerve or into the interfascicular tis-
Regarding axon regeneration, two points are sues of the distal stump.
worthy of special comment: (1) the distinction that 2. Nerve cross-union experiments show that re-
should be drawn between axon regeneration and generating motor axons will enter and grow
functional recovery; and (2) the role of neurotro- down sensory endoneurial tubes, and sensory
pism in axon regeneration. down motor.

782 Anatomy and Physiology of Nerve Injury MUSCLE & NERVE September 1990
3. Regenerating motor axons will occupy the en-
doneurial tubes of a cutaneous nerve graft and
grow rapidly and readily along them.
4. An analysis of the results of nerve repair are
consistent with the random entry of regenerat-
ing axons into the endoneurial tubes of the dis-
tal nerve end.
Neurotropism as a force converting order out of
chaos at the suture line is a nonevent. Physical in-
fluences outlining paths of least resistance
through the interface tissues are the principal de-
terminants of the direction taken by regenerating
axons after they leave the proximal nerve end.
Under such circumstances, we may well ask what
are the chances of regenerating axons reaching
and reinnervating functionally related endoneu-
rial tubes, particularly in view of the many haz-
ards to be overcome enroute.
Disregarding the well-established influence of
suture line scarring, other less obvious hazards
that are just as damaging include:
1. Discrepancies that have developed in the cross-
sectional dimensions of the two nerve ends
(Fig. 15).
FIGURE 15. Diagrammatic representationsof factors at the su-
ture that are responsible for the loss of axons during axon regen-
eration. (From Sunderland S: Nerves and Nerve Injuries. Edin-
burgh, Churchill Livingston, 1979. Used with permission.)
Anatomy and Physiology of Nerve Injury
Discrepancies in the fascicular patterns at the
nerve ends so that fasciculi are opposed to
epineurial tissue and vice versa (Fig. 4).
The absence of any branch fiber localization at
the level of the repair particularly in mixed
motor and sensory nerves (Fig. 16). The
chances of useful regeneration are improved,
however, at levels where some branch fiber lo-
calization is present.
At levels where there is no branch fiber local-
ization, the numbers of nerve fibers represent-
ing individual branches becomes a factor influ-
encing the entry of axons into functionally
related endoneurial tubes. Thus, in the median
36mm 38mm
132 m m 136mm
FIGURE 16. The effect of fascicular branch fiber localization on
the outcome of axon regeneration. The notations are those given
in Figure 6. The arrangement in the lower pair favors the misdi-
rection of regenerating axons into foreign endoneurial tubes.
(From Sunderland S: Nerves and Nerve lniuries. Edinburgh,
Churchill Livingston, 1979. Used with permission.)
MUSCLE & NERVE September 1990 783
 nerve in the mid-forearm, where the sensory fi-
bers for the hand greatly outnumber motor fi-
bers, the former will have a decided advantage
in the competition for endoneurial tubes SO
that the prospects for sensory recovery are
much better than those for motor recovery.
Clearly, large numbers of regenerating axons
are inevitably lost at the suture line so that rein-
nervation is always incomplete and imperfect. A
further minus is that, with delayed nerve repair,
even those axons entering functionally related en-
doneurial tubes and reinnervating functionally re-
lated end organs fail to develop fully. This is be-
~~ ~~~ ~~ ~~~ ~
REFERENCES
1 . Sunderland S: The blood supply of the nerves of the up-
per limb in man. Arch Neurol Psychiat~1945;53:91-115
2. Sunderland S: The blood supply of the sciatic nerve and its
popliteal divisions in man. Arch Neurol Psychiatry 1945;
54:283-289.
3. Sunderland S: The blood supply of peripheral nerves:
Some practical considerations. Arch Neurol Psychiatry 1945;
54:280-282.
4. Sunderland S: The intraneural topography of the radial,
median and ulnar nerves. Brain 1945;68:243-299.
5. Sunderland S: Factors influencing the course of regenera-
tion and the quality of the recovery after nerve suture.
Brain 1952;75:19-54.
6. Sunderland S: The relative susceptibility to injury of the
medial and lateral popliteal divisions of the sciatic nerve.
Brit J Surg 1953;41 :300- 302.
7. Sunderland S: Funicular suture and funicular exclusion in
the repair of severed nerves. B r J Surg 1953;40:580-587.
8. Sunderland S: The connective tissues of peripheral nerves.
Brain 1965;88:841-853.
9. Sunderland S: Anatomical features of nerve trunks in rela-
tion to nerve injury and nerve repair. Clin Neurosurg
1970;17:38-62.
10. Sunderland S: Nerves and Nerve Injuries. 2nd Ed. Edin-
burgh, Churchill Livingstone, 1978.
1 1 . Sunderland S: The pros and cons of funicular nerve re-
pair.J Hand Surg 1979;4(3):201-211
12. Sunderland S: The anatomical basis of nerve repair. In
Jewett DL, McCarroll HR, eds. Nerve Repair and Regenera-
tion: Its Clinical and Experimental Basis. St. Louis, CV Mosby
1980, pp 14-35.
784 Anatomy and Physiology of Nerve Injury
cause of irreversible changes in the wall of
shrunken endoneurial tubes which prevent the
maturation of fibers to their original calibre and
degree of myelination. This could contribute to
the permanent reduction in the conduction veloc-
ity of regenerated nerve fibers. The challenge is
to correct or at least modify these adverse factors,
but that is another story.
I hope that sufficient has been said to convince
the reader that the anatomy and physiology of
nerve injury is a subject worthy of the most care-
ful consideration; on that note I shall conclude
this presentation.
13. Sunderland S: The anatomic foundation of peripheral
nerve repair techniques. Orthopedic Clinics of North America
198 1 ;12~245-266
14. Sunderland S, Bedbrook GM: The cross-sectional area of
peripheral nerve trunks occupied by the fibers represent-
ing individual muscular and cutaneous branches. Brain
1949;72:613-624.
15. Sunderland S, Bradley KC: The cross-sectional area of pe-
ripheral nerve trunks devoted to nerve fibers. Brain
1949;72:428- 449.
16. Sunderland S, Bradley KC: Endoneurial tube shrinkage in
the distal segment of a severed nerve. J Comp Neurol
1950;93:411-420.
17. Sunderland S, Bradley KC: Denervation atrophy of the dis-
tal stump of a severed nerve.] Comp Neurol 1950;93:401-
409.
18. Sunderland S, Bradley KC: The perineurium of periph-
eral nerves A m t Rec 1952;113:125-141.
19. Sunderland S, Bradley KC: Stress-strain phenomena in
human peripheral nerve trunks. Brain 1961;84:102- 119.
20. Sunderland S, Bradley KC: Stress-strain phenomena in
human spinal nerve roots. Brain 1961;84:120- 124.
21. Sunderland S, Bradley KC: Stress-strain phenomena in
denervated peripheral nerve trunks. Brain 1961;84:125-
127.
22. Sunderland S, Marshall RD, Swaney WE: The intraneural
topography of the circumflex musculocutaneous and obtu-
rator nerves. Brain 1959;82:116- 129.
23. Sunderland S, Ray LJ: The intraneural topography of the
sciatic nerve and its popliteal divisions in man. Brain
1948;71:242-273.
MUSCLE & NERVE September 1990