Invited reviewMicroneurography as a tool in clinical neurophysiology to investigate peripheral neural traffic in humans
Introduction
Microneurography is a unique method to record neural impulses from human peripheral nerves in situ. Using this method neural traffic can be recorded not only from large myelinated fibers but also from thin unmyelinated fibers. The first successful recording of neural impulses from human peripheral nerves was by Hensel and Boman (1960), who used a glass microelectrode to record single unit afferent discharges from an exposed peripheral nerve of healthy humans. Seven years later, two different Swedish groups reported independently much less invasive recording techniques of human neural discharges. Both groups used metal microelectrodes which penetrated percutaneously without anesthesia into the peripheral nerves in healthy human subjects. Knutsson and Widén (1967) used a platinum–iridium microelectrode, while Hagbarth and Vallbo (1967) employed a tungsten microelectrode. The original method of Hagbarth and Vallbo has become widely used all over the world, and is currently called microneurography.
Using this microneurography technique, afferent discharges from muscle and skin, as well as efferent discharges leading to muscle and skin can be recorded from human peripheral nerves to identify the sensory receptors and the effector organs. Thus identified afferent discharges from muscle spindles, tendon organs, muscle nociceptors, skin mechano-, and nociceptors, as well as activity of postganglionic sympathetic efferent nerves innervating muscle and skin can be separately analyzed. Recordings of afferent discharges from muscle spindle are useful to analyze neural mechanisms of motor control. Recordings of afferent discharges from cutaneous mechanoreceptors provide objective signals related to skin mechanoreception such as vibrotactile sensation. Paresthesia was reported to be related to abnormal ectopic discharge generation in sensory fibers (Ochoa and Torebjörk, 1980, Ochoa and Torebjörk, 1980). Cutaneous mechanoreceptive afferent discharges contribute to not only sensory functions but also fine motor control. Recordings of afferent discharges from nociceptors in muscle and skin provide valuable objective signals related to pain and other sensation such as an itch. Recordings of sympathetic efferent activity are essential to understand the neural mechanisms of autonomic functions.
Recordings of efferent discharges of α-motor fibers are not practical, because α-motoneuronal efferent activity can be more readily detected by EMG. There have been only a few reports in which skeletomotor activity was microneurographically recorded (Ribot et al., 1986) or conduction velocity of single α-motor fibers was measured using a combination of microneurographic and spike-triggered averaging techniques (Kakuda et al., 1992b). Recording of γ-efferent nerve should be useful to analyze mechanisms of fusimotor control of movements and muscle tonus, but there has been only one report concerning this recording (Ribot et al., 1986), and it was not reconfirmed thereafter by other investigators. The poor reports of γ-efferent recordings may be due to some technical problems of microneurography. By applying the microneurographic technique, not only recordings of neural traffic in peripheral nerves, but intraneural electrical stimulation of afferent and efferent nerve fibers (microstimulation) became possible. Using microstimulation, the functions of skin mechanoreceptors (Vallbo, 1981, Torebjörk et al., 1987), muscle nociceptors (Simone et al., 1994, Marchettini et al., 1996), skin nociceptors (Ochoa et al., 1989), skeletomotor fibers (McNulty et al., 2000), and sympathetic efferent nerves (Kunimoto et al., 1991, Kunimoto et al., 1992a, Kunimoto et al., 1992b) were investigated.
Microneurographic studies have been carried out to elucidate various problems related to neural mechanisms in humans under normal and disease conditions. At the early stage of microneurographic research, this technique was used preferably to investigate afferent discharges in myelinated fibers from muscle and skin. An early review detailing this technique was reported by Vallbo et al. (1979). More recent microneurographic studies have mainly focused on investigation of efferent and afferent discharges in unmyelinated C fibers including sympathetic neural traffic leading to muscle and skin called muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA) as well as cutaneous nociceptive units. Sympathetic microneurography has become a potent tool of clinical autonomic testing. Spontaneously discharging sympathetic neural traffic in abundant fibers grouped in muscle and skin nerve fascicles can be more easily recorded as identified multi-fiber activities than as single-unit somatic afferent discharges. Interindividual comparison of neural activity can be done more easily with quantitative analysis in sympathetic neural traffic, particularly in MSNA, than in sensory afferent discharges. Wallin, 1981, Wallin, 1983, Wallin, 1986 has contributed much to the development of sympathetic microneurography, which has been used not only in ground-based laboratories, but also in space. Autonomic neural functions in space have been evaluated using various indirect methods (Mano, 2005) until 1998, when microneurography was first applied for the first time during spaceflight to clarify how microgravity influences sympathetic neural traffic in humans. For this research, three American and one Japanese astronauts mastered perfectly the technique of microneurography. Two of them aboard Space Shuttle Columbia could measure successfully MSNA from the peroneal nerve of their fellow astronauts. It was revealed that MSNA was rather enhanced during the 12th and 13th days of spaceflight and just after returning to Earth (Cox et al., 2002, Ertl et al., 2002, Fu et al., 2002, Levine et al., 2002). The recordings of unmyelinated C afferent fibers from cutaneous nociceptors were become accelerated by introducing a computer-assisted identification method called marking technique.
In the present review, the usefulness of microneurography as a tool to investigate peripheral neural functions in humans will be described with presentation of topics related to recording.
Section snippets
Recording technique of microneurography
Tungsten microelectrodes with an epoxy resin insulated shaft having diameter of about 100–200 μm and a tip diameter of about 1 μm and an impedance around 1–5 MΩ at 1 kHz, are generally used in microneurography to record afferent and efferent discharges from human peripheral nerves. Nerve discharges are recorded as voltage differences between an intraneurally inserted recording electrode and a reference electrode (surface or needle electrode) placed in the vicinity of the recording electrode. The
Sympathetic microneurography as a tool to investigate autonomic neural functions in humans
Autonomic functions in humans have so far been analyzed by autonomic tests mainly based on observation of functions of target organs and measurement of the plasma level of noradrenaline and/or other related substances. Currently, power spectral analysis of heart rate and blood pressure, as well as recordings of sympathetic skin and flow responses, are widely used as autonomic tests in clinical neurophysiology. Instead of these indirect methods, microneurography provides direct measurement of
Afferent discharges from muscle spindle and tendon organ
Microneurography has made it possible to record afferent discharges from muscle mechanoreceptors including activities from the primary and secondary endings of muscle spindle as well as Golgi tendon organs. Careful minute adjustments of the microelectrode tip enables to record multi- and single-unit activities from muscle spindles and tendon organs. Muscle spindle afferents can be identified by its properties: (1) responding to passive muscle stretch; (2) responding only to the taps or
Microneurographic recordings of afferent discharges from muscle and skin nociceptors
Microneurography enables to record afferent discharges in thin myelinated Group III and unmyelinated Group IV fibers from muscle nociceptors, as well as thin myelinated Aδ and unmyelinated C afferent discharges form skin nociceptors.
Effects of sympathoexcitation on muscle and skin afferent discharges
In animal studies, the direct sympathetic modulation of muscle spindle function is known by several studies. Macefield et al. (2003) examined this sympathetic modulation in humans. They recorded muscle spindle afferent (20 primary and 17 secondary) in healthy subjects and examined the effects of maneuvers that increase MSNA. They found that the maneuver that activates sympathetic outflow to muscle did not alter spontaneous spindle afferent discharge, and concluded that the direct sympathetic
Issues concerning the safety of microneurography
Regarding the microneurography technique in which a tungsten microelectrode is inserted into human nerve fascicles, the safety issues must be addressed. The subject sometimes feels transient dysesthesia or burning sensation along the explored nerve when the electrode tip reaches the nerve fascicle, but these complaints vary markedly among subjects. Pain sensation is much less complained in comparison with conventional electromyographic examination using needle electrodes. It is rather rare that
Conclusions
Microneurography provides useful peripheral neural information concerning autonomic, motor and sensory functions in humans. This method is a particularly important tool to analyze directly neural mechanisms underlying autonomic functions under normal and abnormal conditions. Sympathetic microneurography has achieved an stable position in human autonomic testing. By using this method, the detailed neural mechanisms underlying autonomic dysfunctions often encountered in neurological diseases such
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