7 Neurophysiologic Testing in Pain Management

7 Neurophysiologic Testing in Pain Management
The Massachusetts General Hospital Handbook of Pain Management

Neurophysiologic Testing in Pain Management

Annabel D. Edwards

As to pain, I am almost ready to say the physician who has not felt it is imperfectly educated.
—R. Weir Mitchell

I. Neurophysiologic testing in pain practice
II. Useful tests

1. Quantitative sensory testing

2. Nerve conduction velocity and electromyography

3. Quantitative sudomotor axon reflex testing and resting sweat output

4. Others
III. QST equipment

1. Thermal stimuli

2. Vibration stimuli

3. Mechanical stimuli

4. Electrical stimuli
IV. Uses of QST in the MGH Pain Center

1. Clinical applications

2. Research applications
V. Conclusion
Selected Reading

Specialized neurophysiologic testing techniques have been used at the Massachusetts General Hospital (MGH) Pain Center for more than 5 years. This chapter will review neurophysiologic testing and its utility in pain practice and research.
Pain signals are communicated through the peripheral and central nervous systems and interpreted supraspinally. Parts of the nervous system that are not normally involved in pain transmission, such as the sensory, sympathetic, and parasympathetic systems, can become involved in pain processes in certain disease states and after injury or sensitization. Thus, activities in the various afferent systems overlap, connect, or change functionally both anatomically and at the cellular and molecular levels, creating a particularly complex challenge for the diagnosis and treatment of pain problems. Neurophysiologic testing is useful because it does the following:

Helps to detect underlying pathology

Helps to define mechanisms

Helps to anatomically localize pain instigators

Helps to focus treatments on mechanisms

Helps to predict if patients will respond to particular treatments by clarifying mechanisms

Used sequentially, helps to monitor disease progress and response to treatment

May have medicolegal applications

Advances pain research by providing quantitative and reproducible measures of pain and its various mechanisms
In clinical practice, neurophysiologic testing is useful when a diagnosis is elusive, or when a pain problem has been refractory to treatment. Testing may uncover the mechanism of the pain and direct treatment appropriately. Neurophysiologic testing is time consuming and not widely available, and it is not appropriate for all pain patients. To get maximal benefit from this testing in the clinical setting, patients and tests should be selected on the basis of a reasonable likelihood that the testing will help direct treatment. Figure 1 summarizes the utility of various tests in different parts of the nervous system.

Figure 1. Peripheral nervous system. NCV, nerve conduction velocity; EMG, electromyography; QST, quantitative sensory testing;QSART, quantitative sudomotor axon reflex testing; RSO, resting sweat output.

Quantitative sensory testing (QST) is a useful clinical and research tool that has been adopted in many pain centers. Other neurophysiologic tests have less applicability to pain practice but are used occasionally to aid diagnosis. In most centers, the latter are carried out exclusively in the neurology clinic.
1. Quantitative sensory testing
Quantitative sensory testing is a noninvasive form of somatosensory testing, and the tests are relatively simple to perform. QST provides information on the activity of the entire afferent pain pathway from the periphery (receptor) to the brain (supratentorium). It tests high-threshold pain and temperature-sensing mechanisms by measuring subjective responses to quantified sensory and painful stimuli applied to the skin. Measured stimuli (most commonly thermal) are used to invoke pain responses and identify alterations in threshold such as those that occur in abnormal pain states such as allodynia and hyperalgesia (see Chapter 1).
Tests that fit into the QST category measure responses to thermal, mechanical (light touch and pinprick), vibratory, and electrical stimuli. These tests are geared mainly to explore the function of the primary nociceptive afferents (Ad and C fibers) as well as Ab fibers. Because these fibers respond to specific types of stimuli, tests are chosen to match them (see Fig. 1). Common findings and their association with various pain processes are listed in Table 1.

Table 1. Pain processes and their association with test findings

QST utilizes subjective responses to accurately calibrated sensory stimuli. Thus, although the stimuli are quantitative, the responses are susceptible to factors that depend on the patient and can result in confusion and inaccuracy, such as the following:

Unwillingness or inability to pay attention and to respond accurately

Distractions and discomfort during testing

Inability to understand directions and use equipment

Medical problems (known and unknown)

Use of medications
Other potential confounding factors include faulty equipment, failure to adhere to standard protocols, and the lack of normative data for particular testing sites. Tremendous variation exists between centers in the methods and interpretations used. An important challenge for pain clinicians and researchers is to reach a consensus on testing methodology so that results are broadly applicable across patient populations.
QST devices and techniques have developed rapidly over the last few years. Several companies specialize in making accurate devices. The most common devices create quantified stimuli including temperature (hot and cold), vibration, electrical stimuli, and punctate pressure. These stimuli are more reproducible and measurable than are the standard screening stimuli because they are delivered by well-calibrated systems.
2. Nerve conduction velocity and electromyography
Although electromyography (EMG) is not a test of sensory or pain function, it is commonly used in conjunction with sensory nerve conduction velocity (NCV) studies to provide information about the function of the peripheral nervous system and to aid in the diagnosis of disease processes underlying pain. These tests are invasive (involving the placement of electrodes into nervous tissue and muscle), do not measure central nervous system (CNS) activity, and are sensitive only to large fiber activity (i.e., sensory and motor, not pain).
However, the tests are useful for localizing the specific anatomic site of a lesion that might be causing pain. In fact, three of the most common conditions identifiable by EMG and NCV (peripheral neuropathy, radiculopathy, and carpal tunnel syndrome) frequently present with pain. The tests involve stimulating the periphery electrically, and measuring the amplitude and latency of the responses in various proximal locations (up to the level of the dorsal root ganglion and anterior horn cells). EMG and NCV help to localize the lesion and determine whether it is axonal or demyelinating; whether it is motor, sensory, or mixed; whether it is focal, multifocal, or diffuse; and the age, severity, and prognosis of the lesion. Referral of pain patients for NCV and EMG testing is appropriate when the diagnosis of neurologic dysfunction associated with pain is unclear or unconfirmed.
3. Quantitative sudomotor axon reflex testing and resting sweat output
An increasingly used somatosensory modality is quantitative sudomotor axon reflex testing (QSART). QSART is sensitive and reproducible in demonstrating small fiber neuropathies, which it does by testing a specific neuronal pathway and the sweat response it produces. This activity is subserved by the autonomic nervous system, which plays an important role in pain modulation and perception, especially in small fiber neuropathies and in complex regional pain syndrome (CRPS), in which pain processes derive a significant contribution from sympathetic activity (neuronal or humeral).
Recent evidence suggests that sweat test activity correlates well with symptoms in CRPS. Patients with painful diabetic neuropathy also display increased sweat activity related to sympathetic over activity. The resting sweat output (RSO) test is similar to the QSART, but it measures only resting activity, which is an indication of spontaneous sympathetic activity.
4. Other tests
Vasomotor function tests
Vasomotor function tests are another way of demonstrating autonomic lability. They include bilateral temperature measurement, the Valsalva maneuver, deep breathing, the tilt test (measuring heart rate and blood pressure), and blood flow variations. The tests take a great deal of time, patience, and experience to conduct reliably, and they are less applicable in pain practice than in general neurologic and medical practice. However, they are occasionally indicated in patients with pain, especially when a diagnosis is needed before provocative tests can be arranged or when provocative tests are not available.
Single-unit nerve studies
Single-unit nerve studies, performed in academic centers, define abnormalities of specific fiber types (e.g., C-fiber activity that cannot be defined using conventional nerve conduction studies).
Laser doppler fluximetry
Laser Doppler fluximetry is a technique that evaluates superficial capillary flow in the face and extremities, thereby revealing asymmetries in sympathetically mediated vascular tone in areas of autonomic dysfunction.
Laser-evoked potentials
This new test is not widely available. It is noninvasive and measures the function of pain pathways in neuropathic pain. The skin is heated by a laser probe that activates Ad and C fibers. Electrical activity is measured at the skull and Ad and C-fiber activities are identified by their respective latencies (late and ultra-late).
1. Thermal stimuli
Because pain and temperature sensitivities are closely related (both being transmitted to higher centers by small, high-threshold fibers—C fibers—with contributions from Ad fibers) via the lateral spinothalamic tracts, thermal sensory tests are an excellent measure of neural pathology producing pain. To test thermal stimuli in the clinical setting, a device is used that can create temperature changes at a set rate and within specific limits to avoid heat or cold burns. (For research purposes, the device allows more extreme temperature settings.)
A thermode, which is placed flat against the skin, creates an area of temperature change. The size of the thermode must be selected for the individual since variations in size alter the results. Site selection is critical, and the literature contains many recommendations for sites based on areas of pain. For example, to test S1, the thermode is placed on the dorsum of the foot just proximal to the fourth and fifth toes and spaced equally between them.
Protocols have been developed for various forms of patient testing. These include specifics about how the equipment is programmed, as well as what questions are asked of the patients during testing. For example, the usual starting temperature of the thermode is 32°C. The temperature is changed at the rate of 1° per second. The patient is asked to push a button when a temperature change is first detected and again when the sensation becomes painful. These details are crucial to maintaining a common language among practitioners and researchers.
The thresholds measured are called warm sensation (WS), cold sensation (CS), heat pain (HP), and cold pain (CP). Normal thresholds are not exact, although in most cases, the normal for WS (i.e., the amount of temperature change it takes to detect an increased temperature from baseline) and CS (i.e., the amount of temperature change it takes to detect a decreased temperature from baseline) is within 1°or 2°C from the start. Heat pain usually occurs near 45°C. Cold pain seems to vary the most but usually does not occur until around 10°C or lower. The QST device can also be used to create non-noxious warm and cool stimuli to identify heat and cold allodynia.
2. Vibration stimuli
The vibration test assesses larger Ab fiber function. The vibration device must make solid, even, and balanced contact with the skin. The pressure applied to the skin must be reliably controlled, as excess pressure can change the function of the nerves. These devices typically have a vibratory range of about 0 to 130 microns and an ability to deliver stimuli at a rate of from 0.1 to 4 microns per second. Site selection is critical, and sites are recommended in the literature. For example, vibration testing for S1 would be done on the plantar surface of the foot, between the fourth and fifth toes on the metatarsal head.
3. Mechanical stimuli
The most commonly used device for quantifying mechanical stimuli is a set of von Frey filaments. These are monofilaments of different thicknesses, which, when placed on the skin and made to bend, create a reproducible and reliable calibrated force. They are arranged in order of increasing mechanical force, starting at around 1.65 to 6.65. These numbers represent the common logarithms of the forces (expressed in 0.1 g) required to bow the filaments. A lowered or raised pain threshold can be detected, as can areas of primary and secondary hyperalgesia.
These filaments are commonly used in research and occasionally in clinical practice. Although full testing can be extremely time consuming, a few standardized filaments can be selected to represent a relevant range for routine clinical purposes (e.g., to test for loss of sensation in peripheral neuropathy).
Another mechanical test involves the use of a pin that is rhythmically applied to the skin with just enough force to cause a slight prick sensation. It is touched to the skin about every 2 seconds (but no more than 3 seconds). In normal skin, the repetitive C-fiber stimulation does not escalate the pain, whereas in patients with hyperalgesia, the repetitive stimulation results in increasingly more discomfort within about eight repetitions.
Tactile allodynia can be identified using a light touch stimulus, for example the examiner’s fingers, a cotton-tipped applicator, or a camel’s hair paintbrush. The patient’s responses to such stimuli are compared from side to side as well as with other body areas.
4. Electrical stimuli
The use of electrical stimuli is a research tool only. In this modality, electrodes placed on the skin deliver stimuli at three different frequencies: 2000 Hz, 250 Hz, and 5 Hz. This is not considered a “normal” stimulus (i.e., it is not what the sensory nerve was meant to respond to), and it does not activate the nociceptor, but it is thought to activate a specific fiber type at each frequency: large myelinated Ab fibers at 2000 Hz, Ad fibers at 250 Hz, and small unmyelinated C fibers at 5 Hz.
1. Clinical applications
The primary uses of QST in the clinical practice of the MGH Pain Center include clarification and confirmation of mechanisms, pain diagnoses, and documentation of responses to treatment. It is also helpful in certain difficult and refractory cases to document changes in treatment efficacy so that adjustments can be made on the basis of formal testing rather than on the basis of subjective assessment by the physician. The tests used most often for clinical assessments at the MGH Pain Center are the following:

Thermal thresholds to warmth and coolness

Pain thresholds to heat and cold

Vibration-detection thresholds

Sensation to pinprick

Thresholds to mechanical sensation and pain by von Frey filaments
2. Research applications
Tests used for research at MGH include those used clinically and the following:

Perception and pain thresholds to controlled electrical current

Blood flow changes as measured by laser Doppler
Because QST devices are so accurate, the stimuli are consistently repeatable, and normative data rapidly are being amassed, these testing techniques have a solid role in research. Mapping of the brain areas involved in the perception of different types of pain (using evoked potentials, functional magnetic resonance imaging, magnetoencephalography, and positron-emission tomography) is just one way in which these tests can be applied. Responses to new techniques such as spinal cord stimulation can also be monitored using QST. The pain field is an exciting area for research, and QST provides a useful tool for quantifying pain stimuli and identifying pain mechanisms.
This chapter describes some of the neurophysiologic tests used in pain management. Some of these tests (chiefly those used to aid in the diagnosis of disease) need to be conducted by experienced personnel and are usually available only in a hospital setting, not in pain clinics. The most useful tests in the pain clinic are those incorporated in QST.
Because QST is essentially noninvasive and causes little discomfort, it is widely applicable. Although the tests are time consuming, which restricts their clinical use, they are a valid means of assessing treatment efficacy at a time when it is becoming mandatory to monitor treatment effects They are also a useful research tool.

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