Importance of clinical neurophysiological tests in the evaluation of pain: Indispensable in complex pain conditions

EMG with neurography

EMG with neurography is the conventional method for investigation of the peripheral nervous system. From its development back in the 1940s and the 1950s it has become the most used electrophysiological investigation of the peripheral nervous system as well as musculature.

The principle is easy: In neurography, when stimulating a peripheral nerve electrically at a distal and proximal site and recording the compound muscle potential from a muscle innervated by this nerve, one may determine the distal motor latency, the conduction velocity as well as the amplitude of the compound muscle potential.

One may determine whether the nature of a potential nerve damage is predominantly demyelinating, i.e. damage to the myelin surrounding the large nerve fibers producing increased distal latency and reduced conduction velocity, or axonal, i.e. damage to the axons themselves as shown by a reduced motor amplitude.

For determination of the function of sensory nerve fibers, the procedure is even simpler. One may stimulate electrically within the innervation territory of the nerve in question and record the sensory potential directly over the nerve (or vice versa), and thereby assessing amplitude and sensory conduction velocity. When combined with EMG, where a needle is inserted into the muscle and the patient is asked to voluntarily contract the muscle, valuable additional information is obtained.

Neurogenic or myogenic lesion?

The neurophysiologist may, based on the pattern of pathological changes within a muscle, decide whether the lesion is neurogenic, i.e. due to a nerve lesion, implying that the changes observed in the muscles are secondary to a lesion of the motor nerve supplying the muscle, or myogenic, i.e. a primary lesion within the muscle fibers itself. The distinction may sometimes be difficult, e.g., in the case of an inflammatory process in the muscle, i.e. myositis, but in most cases the EMG findings will clearly be either of a neurogenic or myogenic nature.

Limitations of nerve conduction studies

It is important to be aware that the nerve conduction studies have their clear limitations, allowing only investigation of the accessible main nerves in the human body, mostly the major nerves of the extremities. EMG, on the other hand, has a more widespread use because more muscles are accessible for investigation. Many nerves in the proximal parts of the extremities, on the body trunk or in the face, may therefore be examined only by means of EMG.

The case illustrates well these principles

This is well illustrated in the case study by Jääskeläinen et al. [1] where the authors used a combination of neurography and EMG. They investigated the sensory nerves of the inferior alveolar nerve, whereas other nerves have been examined only by means of EMG, by inserting an EMG-needle in the masseter and temporal muscles as well as in the lateral pterygoid muscle. They found two findings of principal importance: (1) spontaneous activity, i.e. positive sharp waves and/or fibrillation potentials, which is sign of denervation of the muscle. Spontaneous activity may develop 2-3 weeks following a nerve lesion and indicates an active denervation process. (2) Polyphasic MUP's of long duration, and are signs of reinnervation. In the present study the investigation was performed nine months after the onset of symptoms, and shows a combination of an acute and a chronic neuropathy.

Only thick, myelinated fibers can be studied with EMG with neurography

Since functions of thin nerve fibers cannot be assessed by EMG with neurography and pain is normally transmitted by small nociceptive fibers, EMG with neurography may seem useless in pain conditions. However, this may be a dangerous conclusion, as elegantly demonstrated in the case report [1]: It is true that EMG with neurography may not investigate the thin nerve fibers responsible for the pain of the patient, but pain may be a symptom of a neuropathy or a neurogenic lesion. EMG with neurography can be extremely useful in diagnosing a neurogenic lesion.

In the present case, the patient had been complaining about facial pain for several months. Clinicians had made a diagnosis of trigeminal neuropathy. However, from the history of her pain condition, the diagnosis of trigeminal neuralgia was not likely, since she also had a more constant pain and not only the characteristic attacks of pain, separated by pain-free intervals, that are so typical for trigeminal neuralgia. She also had sensory deficits, not typical for trigeminal neuralgia. So, already from a pure clinical point of view, as pointed out by Jääskeläinen et al. [1] the diagnosis of trigeminal neuralgia should have been questioned.

Methods for evaluation of functions of small nerve fibers: quantitative sensory testing (QST), skin biopsy, quantitative sudomotor axon reflex test (QSART), axon reflex flare

The patient was examined not only by EMG with neurography, but also with a method of small-fibre function. QST (quantitative sensory testing) and more specifically assessment of thermal thresholds, investigating the function of small temperature mediating nerve fibers was used. Measurement of the heat pain thresholds is a test of nociceptive nerve fibers, but a combination of all thermal thresholds, will yield information about the functions of a subgroups of the afferent small nerve fibers. In the actual case, the authors found only a slightly elevated warm detection threshold in the distribution of the left mental nerve.

The generation of nociceptive impulses depends on changes on the membrane of the small nerve fibers, the A-delta fibers and C-fibers. In general, it is important to be aware of the limitations of the tests of small fiber functions: there is no gold standard among several methods available today: skin biopsy, assessment of thermal thresholds (QST), quantitative sudomotor axon reflex test (QSART), and axon reflex flare. All of these methods have their advantages and limitations.

Skin biopsy is the most sensitive method for determination of small fiber damage, but may not differentiate between the different small nerve fibers and does not say anything about function.

QST measurement of thermal thresholds is a psychophysical and thereby non-objective method of the small nerve fibers, but is otherwise easy to perform, may differentiate between the A-delta and the C-fibers and assess thermal hypersensitivity.

QSART tests the efferent sympathetic C-fibers, and although it is objective, does not evaluate the sensory part of the experience of pain.

Axon reflex flare test determines the size of flare produced by electrical stimulation of the skin. It is objective, but slightly painful [2].

Important limitations of small fiber tests in patients with pain

It is of utmost importance to be aware of the fact that there are no convincing differences in the results of these tests between patients with or without pain. This is true for patients with polyneuropathies as well as those with peripheral mono nerve lesions (for references, see [3]).

Although some studies in patients with polyneuropathies have shown a significantly larger impairment of the small nerve fibers in patients with pain compared to those without pain, the small-fiber tests are not able to differentiate between those who have pain and those who are painless. Thus, at the moment we do not have tests that can detect the important mechanisms responsible for the generation of pain.

Hyperexcitability of peripheral nociceptive neurons may be regarded as the main and perhaps most important peripheral pathophysiological mechanisms for the generation of pain. However, this phenomenon is detectable only when recording directly from nociceptive nerve fibers with microneurography. In this author's opinion, microneurography will remain a method restricted for research. Nevertheless, given the assumption that damage or changes of small nerve fibers is an important prerequisite pre-requisite for neuropathic pain, it must be important to test their function. Painful conditions due to a pure involvement of the large myelinated nerve fibers are rare.

Combining available neurophysiological methods in clinical practice

In the present case [1], a test of small fiber function was included. For testing of small fiber function in the face, only thermal testing is technically (and ethically) possible. Jääskeläinen and coworkers did find alterations by elevated warm detection thresholds with the QST-method, indicating C-fiber lesions. It was, as emphasized by the authors, the combination of EMG with neurography and small fiber testing and reflex-studies that allowed a determination of the topographic site of the lesion. In addition, interestingly, they also found a predominant damage to the large myelinated nerve fibers that in this case will reflect the mechanisms of the nerve lesion. These findings suggest a primary compression injury of the nerves in question. They verified this to be the case. When a peripheral nerve containing both large myelinated and small nerve fibers is compressed, e.g., by a metatastatic mass, it will first damage the myelin surrounding the large nerve fibers. This will produce neurophysiological findings characteristic for this type of lesion. It will eventually, when the cause of the nerve lesion develops, also result in damage of the axon, as shown by the EMG-findings, and damage of the small fibers.

Other well known and not uncommon causes of nerve obstructions, the many different peripheral nerve entrapments, will show the same pattern, i.e. the large myelinated nerve fibers will be most damaged [4].

The present case report is first and foremost an elegant example of how an elaborate clinical neurophysiological investigation may provide valuable information of the nature of the nerve damage, it may indicate the site of a lesion and also indicate some of the mechanisms involved. The authors are experts on facial pain. Not all neurophysiological laboratories would be able to provide a similar comprehensive investigation.

The most important message as emphasized by the authors, is howa combination of neurophysiological tests, including EMG with neurography, maybe useful in diagnosing a neuropathy responsible for a painful condition.

Concluding remarks

In this editorial comment, I want to support the authors' important message, to strongly recommend that EMG with neurography in combination with other neurophysiological tests are performed during the assessment of a painful condition in order to reveal any neurogenic lesion, not for the demonstration of the mechanisms of pain.

EMG with neurography and the available tests of small fiber function will be able to diagnose a neuropathy responsible for pain, but not the mechanisms for the generation of the pain. For the patient, the diagnosis of a peripheral nerve injury or neuropathy will be most important.