Microneurography was developed by Karl-Erik Hagbarth and Åke Vallbo in Uppsala, Sweden in the early 1960s, and the first definitive papers were published in 1968 (on cutaneous and muscle afferents). With this invasive technique it is possible to study how receptors in muscle, skin, and joints behave under natural conditions and how the sympathetic innervation of skin and muscle normally behaves. A number of authoritative reviews of the technique and the information obtained thereby have been published.

Microneurography has generated many data that illuminate normal neural mechanisms and the disorders that occur in a wide variety of disease processes. The development of conduction block in single axons has been studied in microneurographic recordings, as has the ectopic activity responsible for paresthesias. It is also possible, for example, to record compound sensory action potentials containing identifiable deflections due to large and small, myelinated and unmyelinated axons. However, this can be done almost as readily and less invasively using near-nerve needle recordings.

Overall, microneurography seems to be of limited diagnostic value. There are four main reasons. First, it takes skill and perseverance to obtain satisfactory recordings. Second, only a few satisfactory recordings from single axons can be obtained in any one session, too few for meaningful statistical comparisons against control values while, with population responses involving many axons, the recorded activity varies with the position of the microelectrode within the nerve fascicle. As a result, the intensity of neural activity can vary greatly from experiment to experiment. Third, if pathology leads to a loss of activity (rather than activity that is preserved but abnormal), as in autonomic failure, no activity will be recorded. This then begs the question of whether the absence of activity is due to technical failure or the pathologic process. Finally, the trauma of the study is a consideration, not because of discomfort, but because, conceivably, the microelectrode could damage the few surviving axons in a patient with, for example, amyotrophic lateral sclerosis, or exacerbate the pain of a patient with a complex pain syndrome.

While microneurography has resulted in major changes in thought about the nature of the feedback that the nervous system receives from peripheral receptors and how it uses that feedback for perception and for movement, this chapter will focus on findings that shed light on clinical phenomena. The reader is referred to previously published reviews for more comprehensive treatises on normal physiology.

Recording technique

The basic technique has changed little since first described. Most authorities use a microelectrode made from tungsten with a shaft diameter of approximately 200 μm, insulated to the tip. The greater the diameter, the more that penetration of a fascicle hurts; a diameter of less than 200 μm is not sufficiently rigid. The experimenter inserts the microelectrode manually through the skin to impale the peripheral nerve. Commonly, weak electrical stimuli are delivered through the electrode and the experimenter hones in on an appropriate nerve fascicle, guided by the evoked paresthesias (when seeking a cutaneous fascicle) or the twitch contraction (when seeking a motor fascicle). Vallbo and colleagues initially insert a low-impedance electrode to locate an appropriate fascicle and then use its location to guide the insertion of the recording microelectrode, the impedance of which has been decreased to near-optimal levels. Others rely on the passage through the skin and the subcutaneous and perineural tissue to remove insulation and reduce the impedance to a satisfactory level. When in place, the optimal impedance of the electrode is perhaps 50 kΩ for multi-unit recordings and some 100 to 150 kΩ for single-unit recordings (though higher impedances may assist single-unit C fiber recordings).

Once the experimenter has manipulated the tip into the fascicle, afferents in that fascicle can be activated, for example by tapping on the muscle tendon or scraping the skin ( Fig. 14-1 ). The activation of mechanoreceptors creates an auditory signal that can be used to guide further small adjustments of the electrode. The electrode is not fixed securely because external fixation leads to electrode dislodgement when minor movements inevitably occur. It is stabilized at its proximal end by a coiled insulated copper wire to the preamplifier and at the recording end by the rigidity of the tissue into which the electrode has been inserted. Nevertheless, minor movements—particularly those that displace skin at the recording site—can jeopardize the recording. This creates an issue for motor control studies because the range of movement that can be studied is small, and consequently it is prudent not to generalize too far about, for example, the role of the fusimotor system in normal motor behavior (see below).

Multi-unit responses to cutaneous stimuli (median nerve). A , Responses to moderately heavy touch stimuli. Note the “on” and “off” responses. B , Responses to scraping the skin with sandpaper. Lower traces illustrate the raw neurogram and upper traces the “integrated” neurogram. In A , the amplitude discriminator has been used to eliminate most of the noise, while in B the neurographic activity is not so treated.

(From Burke D, Mackenzie RA, Skuse NF et al: Cutaneous afferent activity in median and radial nerve fascicles: a microelectrode study. J Neurol Neurosurg Psychiatry, 38:855, 1975, with permission.)

The insulation created by the tissue that surrounds a nerve fascicle is very effective. It is virtually impossible to record the activity of single axons if the microelectrode tip is just outside a fascicle, even if the discharge of that axon is used to trigger averages of many sweeps. Once the microelectrode is within a fascicle, axonal activity can be recorded readily, and it is then possible for the experimenter to focus on spontaneous neural discharges (e.g., the bursts of activity that occur in sympathetic efferent axons innervating skin or muscle) or the neural discharge evoked by mechanical stimuli, such as tapping on the muscle belly or tendon (with a motor fascicle) or stroking the skin (with a cutaneous fascicle).

Obtaining stable recordings from single axons requires skill and patience. It is helpful if the axon has a background discharge because, unless the discharge of the axon can be heard, it may be difficult to know that the electrode is close to it. This means that the recordings inevitably will be biased toward axons that maintain a background discharge, and this is probably the main reason that there are fewer recordings from group Ib afferents from Golgi tendon organs than from group Ia afferents from primary spindle endings. In addition, because action potential amplitude is a function of the cross-sectional area of the axon, the potentials of large axons will be distinguished more readily from the background noise—perhaps explaining why there are few recordings from cutaneous Aδ axons. Paradoxically, it is relatively easy to obtain recordings from unmyelinated C fibers. This is because they occur in clusters of approximately six or more axons within the cytoplasm of a Schwann cell (the so-called Remak bundle) containing C fibers with different properties, so that a recording from this group of axons can be made quite readily, particularly if they are sympathetic and have a background discharge. The action potentials from myelinated axons commonly have a bifid appearance (in about 75 percent of units, Fig. 14-2, C ). The two peaks represent action potentials at nodes of Ranvier on either side of the impalement of the axon by the microelectrode ( Fig. 14-2, D ). That two peaks are discernible implies that conduction across the internode is slow (see later, in section on Conduction Block). When the action potential has a simple biphasic morphology (as in Fig. 14-2, A ), it could be “normal” or one in which conduction across the impaled internode is blocked.

Three types of action potential morphology. A , “Positive single-peaked” (23 percent). B , “Negative” (1.4 percent). C , “Positive double-peaked” (75 percent): six examples. D , Explanation for positive double-peaked units. If the microelectrode tip impaled the myelin sheath, the current fluctuations at the nodes of Ranvier on each side of the recording microelectrode would contribute to the recorded action potential. If internodal conduction is prolonged, two distinct “positive peaks” would occur (see Figs. 14-3 and 14-16 ).

(From Inglis JT, Leeper JB, Burke D et al: Morphology of action potentials recorded from human nerves using microneurography. Exp Brain Res, 110:308, 1996, with permission.)

The technique has been developed to allow stimulation through the intrafascicular microelectrode (often referred to as microstimulation ). With myelinated axons, activation is likely to occur at the nodes of Ranvier on either side of impalement (as in Fig. 14-2, C and D ). In studies of the perceptual correlates of afferents, this effectively then would be the proximal node because any action potential from the distal node will occur during the refractory period for the proximal node, even when internodal conduction is delayed (see later). With afferents, intrafascicular stimulation has allowed (1) the cortical evoked potentials produced by the stimulated afferents or their reflex effects to be defined, and (2) the perceptual responses associated with activity in single afferent axons to be documented. With efferents, intrafascicular stimulation has been used (1) to produce the twitch contraction of the receptor-bearing muscle to differentiate spindle endings from Golgi tendon organs, as discussed later, and (2) to document the contraction properties of single motor units.

The critical step with single units is to identify the axon. This can be done for afferents by locating the receptor in skin or muscle and characterizing its responses to a variety of stimuli: mechanical, thermal, nociceptive. With α motor axons, the axon will be active only if there is a deliberate, inadvertent, or involuntary contraction of the innervated muscle involving that motor unit, and the neural spike can then be used to spike-trigger average the ongoing electromyographic activity ( Fig. 14-3 ). This then should allow the motor unit action potential to be defined at a latency appropriate for direct conduction from the stimulating site to the muscle. It has been claimed that γ motor axons (which innervate the intrafusal muscle of the muscle spindle) can be identified on discharge characteristics alone, but it would be prudent to retain reservations about such claims because there are scant data on how γ motor neurons discharge in natural acts in animals, and no such data for human subjects. Accurate identification can be time-consuming, and may require maneuvers that displace the skin at the recording site (e.g., a twitch contraction), so that recordings are lost before meaningful data can be obtained from that axon.

An α-motor axon innervating tibialis anterior undergoing activity-dependent conduction block. The traces on the left represent superimposed consecutive nerve action potentials recorded at different stages during the development of conduction block and, after rest, recovery therefrom, for a motor axon discharging in a voluntary contraction. The traces on the right represent spike-triggered averages of surface electromyogram (EMG) of tibialis anterior, each trace consisting of approximately 32 sweeps, corresponding to the neural spikes on the left. The timing of the nerve action potential is indicated by the vertical line. In the top left panel a second positive peak was seen in each recording, though the interpeak interval gradually increased and became highly unstable in the fourth trace. The EMG potential was consistently recordable. In the middle panel ( Block ), the second positive peak was present only in a few sweeps in the upper set of traces. There was no consistent EMG potential. Following rest for a few minutes, a further contraction was performed; the second positive peak was again present in the nerve action potential, and the EMG potential had reappeared ( Recovery ). Note the difference in time base for the nerve action potential and the EMG potential. The longest interpeak interval (fourth set of traces under Pre-block ) was 1.43 msec (indicated by vertical arrow).

(From Inglis JT, Leeper JB, Wilson LR et al: The development of conduction block in single human axons following a focal nerve injury. J Physiol, 513:127, 1998, with permission.)