Chapter 12

PERIPHERAL NERVES

The compound action potential

If we took a 10-mm length of mixed peripheral nerve, for
example, the sciatic nerve, and recorded changes in
electrical potential from one end of it while electrically
stimulating the other end, as illustrated in Figure 12-1A, we
could make some interesting observations that tell us a great
deal about peripheral nerves. Sample records from such an
experiment are shown in Figure 12-1B(1). In the uppermost
trace, the strength of the stimulus is very low, and we see no
response from the nerve. This stimulus strength is
subthreshold. If the strength is raised, a tiny response
appears in the record and, as the strength is increased even
more, the response grows to a maximum value (next to
bottom trace); further increases in shock strength do not
further augment the response. The stimulus strength that just
gives a response is termed a threshold stimulus; any
stimulus of greater strength is suprathreshold. The strength
that just gives the maximal response is a maximal Fig. 12-1. A. Setup for recording the
stimulus; any strength greater is supramaximal. The compound action potential from the
response of the nerve is called the compound action sciatic nerve. B. Sample records taken
at stimulus strengths increasing from
potential. The compound action potential is graded in top to bottom. Trace deflects upward
nature, in striking contrast to the all-or-none response of when left recordng electrode is
single axons. negative with respect to the right one.
Note the graded nature of the
There is a simple explanation for why the response of a compound action potential. (Katz B:
Nerve, Muscle and Synapse. New York,
nerve is graded and that of a single fiber is all-or-none. The McGraw-Hill, 1966)
nerve is composed of many fibers of different diameters,
with these different diameters seemingly distributed at
random throughout the nerve. It turns out that the threshold
for discharge of an axon in response to externally applied current is inversely related to the
diameter of the axon, so that for a large and small axon equidistant from the stimulating electrode,
the large axon will have the lower threshold. Furthermore, if two axons of the same size are at
different distances from the stimulating electrode (that is, one is buried deeper in the nerve or on
the other side of the nerve from the electrode), the one closer to the electrode will pick up more
current and therefore reach threshold at a lower stimulus strength than the one farther away. Thus,
as the stimulus strength was increased in Figure 12-1B, the largest axons closest to the electrode
began responding at lowest stimulus strengths. Then, at higher strengths, smaller axons close to the
electrode and large axons farther away from the electrode responded, and their individual action
potentials were added to the compound action potential. Finally, at maximal stimulus strength,
every axon in the nerve was contributing its own all-or-none action potential, whence no further
increase in the response was possible. It should be kept in mind that at all strengths, the recorded
response is the sum over time of the action potentials of all of the discharging cells.
 The shape of the compound action potential in Figure
12-1 may look like a temporally expanded action
potential followed by an after-hyperpolarization;
however, the positive potential of the compound action
potential does not represent a membrane
hyperpolarization. After-hyperpolarizations are really
too small to contribute much to the compound action
potential. Rather, the biphasic nature of the potential
results from the bipolar extracellular recording setup.
Note that two electrodes were used for recording, one
closer to the stimulus, one farther away, and the
voltage was recorded at one electrode with respect to
the other, i.e., the difference in potential was recorded,
but neither electrode was over inactive tissue. Figure
12-2 shows the events that occur as the compound
action potential is propagating under the electrodes(2).
In A, the action potentials have not yet reached the
recording site; the membrane potential of most cells is
at rest. (Note: Some cells discharge spontaneously.)
Both electrodes are at the same potential; the
difference is zero as shown. The advancing spikes
have reached the first electrode in B; many cells have
reversed their membrane polarities, and the potential at
the first electrode has become negative with respect to
the second. In C, the action potentials have begun to
invade the membranes under the second electrode; the
potential at the first electrode is still more negative
than at the second but less so than in B. The
membranes under the first electrode are already
Fig. 12-2. Axon membrane polarization at repolarized as the action potentials have passed, but
various times during conduction of an action they are still hypopolarized under the second electrode
potential. Shown are polarizations when the
spike is approaching the segment (A), under in D. The potential at the first electrode is now positive
one electrode (B, D), under both electrodes (C), with respect to the second. In E, the spikes have passed
and retreating from the segment (E). The both electrodes; the electrodes are at the same potential
meter, connected to two external electrodes, again, and the difference is again zero. The recorded
shows the polarity of the recorded voltage. configuration is therefore a result of the recording
setup.

The compound action potential is an artifact of the manner in which the nerve was stimulated. It is
doubtful that such a potential is often elicited in nerves under normal conditions of sensation or
movement, but they may occur in some special circumstances. For example, in muscle nerves,
when a person jumps off an object and lands on the ground, a relatively synchronous volley of
action potentials is set up in the group Ia afferent fibers from the quadriceps muscles, and this in
turn results in a relatively synchronous volley in the alpha motoneurons of the quadriceps muscles,
as we will see in Chapter 15. Usually, however, there is a constant, asynchronous trickle of action
potentials coming into the central nervous system and also leaving it. However, the study of the
compound action potential has given us a lot of information about conduction in peripheral nerves.
 
Types of
fibers in
peripheral
nerves
If, now, a greater
length of sciatic
nerve is used in
the same
experiment (say
80 mm of nerve),
a new
phenomenon
appears in the
recording. Figure
12-3 shows a
stimulus-intensity
series (increasing
strength from top
to bottom)
recorded under
these conditions.
At just
suprathreshold Fig. 12-3. Sample records from the sciatic nerve of responses elicited by electrical
strength, a stimuli applied to the nerve 80 mm away. The various components of the compound
response (the A- action potential are labeled where they appear. Shock strengths increase from top to
bottom.
alpha response)
appears in the
record at about 2 msec after the shock artifact. At higher shock strengths, this response grows in
size, and a new response (the A-beta response) appears in the record about 4 msec after the artifact.
Further increases in shock strength result in further increases in both the alpha and beta responses
and the addition successively of the new responses: A-gamma, A-delta and B, and C. Based on the
discussion of the precious paragraph, it is appropriate to assume that the components added to the
response at higher stimulus strengths represent the responses of successively smaller fibers, and
this is indeed the case. Notice also that the responses of successively smaller fibers occur later and
later in time after the artifact. This is because the conduction velocity of an axon is a direct
function of its diameter, and it requires a longer time for the action potentials in more slowly
conducting axons (smaller ones) to travel the 80 mm than for action potentials in more rapidly
conducting axons (larger ones).

These different responses weren't seen in the experiment in Figure 12-1 because the short
conduction distance in that experiment caused the action potentials in all sizes of fibers to arrive at
the recording electrode at nearly the same time; there wasn't sufficient time for differences in
conduction velocity to show up. The individual responses were all bunched up together and were
thus superimposed in the record. Nevertheless, the same fibers were discharging at the same shock
strengths in both experiments.

Take a moment at this point to note in Figure 5-13, that the smallest fibers are the most numerous
by far, whereas the largest are least numerous. In cutaneous nerves, measurements have indicated
 Fig. 12-4. Fiber diameter spectra for a cutaneous (A) and a muscle nerve (B) to indicate the types of
fibers in each and the use of the naming systems of Table 12-1. (Boyd IA, Davey MR: Composition of
Peripheral Nerve. Ediburgh, Livingstone, 1968)

that there are about twice as many A-delta fibers as A-alpha fibers and about 4.6 times as many C
fibers as A fibers(3). Though this is the case, the maximal response (Fig. 12-3) recorded from the
largest fibers, the A-alpha fibers, is many times larger than that recorded from the smallest fibers,
the C fibers. This is because fibers contribute voltage to the recording in proportion to the square of
their diameters. The result is that a fiber 2 times as large as another contributes 4 times as much
voltage to the recording. In our case, the largest A fiber is 22 micrometers in diameter, the largest
C fiber only 1 micrometer in diameter; they differ by a factor of 22, and they contribute voltage to
the recording in the ratio of (22)2:(1)2 or 484:1.

Table 12-1
Two Systems for Classifying Axons in Peripheral Nerve by Diameter
Letter System
Type of Diameter, Conduction General Function
fiber micrometers velocity, m/sec
A-alpha 13-22 70-120 alpha-motoneurons, muscle spindle primary
endings, Golgi tendon organs, touch
A-beta 8-13 40-70 touch, kinesthesia, muscle spindle secondary
endings
A-gamma 4-8 15-40 touch, pressure, gamma-motoneurons
A-delta 1-4 5-15 pain, crude touch, pressure, temperature
B 1-3 3-14 preganglionic autonomic
C 0.1-1 0.2-2 pain, touch, pressure, temperature, postganglionic
autonomic
Roman Numeral System

Fig. 12-4. Fiber diameter spectra for a cutaneous (A) and a muscle nerve (B) to indicate the types of
fibers in each and the use of the naming systems of Table 12-1. (Boyd IA, Davey MR: Composition of
Peripheral Nerve. Ediburgh, Livingstone, 1968)

We find that fibers of particular receptor systems are often separable to some extent on the basis of
their conduction velocities. Table 12-1 summarizes the two different classification schemes for
peripheral neurons based upon their conduction velocity or diameter. The Roman numeral scheme
(lower part of the table) refers to afferent fibers only, whereas the letter scheme (upper part of the
table) includes both afferent and efferent fibers. It may help to note that A-alpha, Ia and Ib fibers
are mostly of muscle origin or destination, and C and group IV fibers are all unmyelinated.
Normally, we use the letter classification scheme to designate cutaneous-afferent fiber types and
the Roman numeral scheme to designate muscle-afferent fiber types, but unfortunately this is not
always the case, so care must be exercised. The fiber diameter spectra of a muscle nerve (B) and a
cutaneous nerve (A) are indicated in Figure 12-4 for comparison with classifications in Table 12-1.
The sum of the two fiber spectra in Figure 12-4 is approximately equivalent in shape to that in
Figure 5-13. Be careful not to confuse the fiber spectra of Figure 12-4 with the compound action
potential of Figure 12-3.

Properties of different types of nerve fibers

Nerve fiber types differ in their response to local anesthetics, in their susceptibility to anoxia, and
in their susceptibility to pressure block. Using the letter classification, these differences are
summarized in Table 12-2. B fibers are most influenced by anoxia, A fibers are most susceptible to
pressure block, and C fibers are most readily blocked by local anesthetics. You may be acutely
aware that hypoxia blocks A fibers before C fibers if you are in the habit of sleeping with your arm
under your head. Upon waking, you may commonly observe that your sense of touch is dulled (you
may have a tingling sensation), but your pain sensitivity is either normal or perhaps even slightly
greater than normal.

Table 12-2
Susceptibility of Different Types of Fibers to
Conduction Block by Various Agents

Effect Most susceptible Intermediate Least susceptible

Block by hypoxia B A C
Block by pressure A B C
Block by local C B A
anesthetics

The measurement of conduction velocities

It is common in peripheral nerve damage that the conduction velocity is slowed drastically in the
damaged portion. For example, in carpal tunnel syndrome, where the bones of the wrist are broken
in such a way that the fragments put pressure on the median nerve, partially blocking conduction, it
is possible to assess the extent of the damage by measuring the conduction velocity of the nerve
and comparing it with that in the normal arm.

Measurement of the velocity is straightforward. First, two sets of stimulating electrodes are placed
on the skin over the median nerve, one near the top of the forearm and one 10 cm closer to the
wrist. It is important that this distance is measured accurately or, at least, that it is the same on both
arms if they are to be compared. Next, a pair of surface electrodes or needle electrodes, pushed
through the skin into the belly of the abductor policis brevis muscle, is used to record the muscle
activity. Recordings are made from muscle because recordings from nerves are more difficult to
obtain. The position of the stimulating electrodes can be checked by stimulating and looking for
abduction and flexion of the thumb, the action of the abductor policis brevis. Electrode position is
adjusted to obtain the lowest threshold for contraction with both pairs of stimulating electrodes.
The nerve is then stimulated with each set of electrodes, while looking at the electromyogram,
EMG, from the muscle and conduction time between the shock artifact and the beginning of the
EMG response is measured. Ten centimeters divided by the difference between the conduction
times for the two electrodes is the maximum conduction velocity for axons in the nerve. Two pairs
of electrodes are used instead of just one because this procedure eliminates the need to estimate and
compensate for the utilization time in the nerve, i.e., the time it takes for the membrane potential to
reach the critical firing level and discharge a spike, and the delay in transmission at the
neuromuscular junction, that is, the time it takes for chemical transmission (see chapter on
synapses). In the normal individual the velocity should be nearly the same in both arms.
Tarsal tunnel syndrome
is the lower limb
equivalent of carpal
tunnel syndrome, but
rarer. In tarsal
syndrome, there is
compression neuropathy
of the posterior tibial
nerve associated with
burning pain and Fig. 13-5. Recordings of compound action potentials (arrows) in the medial and
paresthesia in the toes lateral plantar nerves in a normal person (A) and in a patient with tarsal tunnel
syndrome (B). Note that tarsal tunnel syndrome is accompanied by slowing of
and on the sole of the
conduction and reduction in amplitude of the compound action potential. (Oh
foot. Figure 12-5 shows SJ, Sarala PK, Elmore RS: Ann Neurol 5:327-330, 1979)
recordings from the
medial and lateral plantar nerves of a normal person (A) and a patient with tarsal tunnel syndrome
(B). Note that the compound action potentials are smaller and later in the patient than in the normal
person, because of the slowing of conduction in some fibers and block of conduction in others.
Conduction velocities measured in normal records are 41.25 and 34.80 m/sec respectively, whereas
those in the patient are 26.10 and 17.78 m/sec, a slowing of 37% and 49%, respectively.

Summary
The compound action potential is the graded response of a peripheral nerve to electrical
stimulation. It is graded because axons of the nerve are of differing diameters, and their thresholds
to externally applied current vary with diameter. The conduction velocity of an axon is a function
of its diameter, so the fastest component of the compound action potential is contributed by the
fastest and largest fibers, whereas later components are contributed by slower and smaller fibers.
Fibers contribute voltage to the compound potential in proportion to the square of their diameters.
The result is that large fibers, though they are fewer in nerves, give the largest components to the
compound action potential. There are two classification systems for peripheral nerve based on
conduction velocity. The letter scheme is for both afferent and efferent fibers. A and B fibers are
myelinated; C fibers are not. The Roman numeral system is only for afferent fibers. Groups I, II
and III are myelinated, group IV is not. The letter scheme is most often used for cutaneous fibers,
the Roman numeral scheme for muscle afferent fibers. B fibers are most sensitive to hypoxic block;
A fibers are most sensitive to pressure block; and C fibers are most susceptible to anesthetic block.

Suggested Reading
1. Hodgkin AL: Evidence for electrical transmission in nerve. Part I. J Physiol (Lond) 90:183-
210, 1937.
2. Hodgkin AL: Evidence for electrical transmission in nerve. Part II. J Physiol (Lond)90:211-
232, 1937.
3. Junge D: Nerve and Muscle Excitation. Sunderland MA, Sinauer, 1976.
4. Katz B: Nerve, Muscle, and Synapse. New York, McGraw-Hill, 1966.
5. Lloyd DPC: Neuron patterns controlling transmission of ipsilateral hind limb reflexes in
cat. J Neurophysiol 6:293-315, 1943.
6. Patton HD: Special properties of nerve trunks and tracts. In Ruch TC, Patton HD (eds):
Physiology and Biophysics, 19th ed. Philadelphia, WB Saunders, 1965.