A Conceptual Model of Pain: Measurement and Diagnosis
In part one of this series,1 the author described a conceptual model of pain based on electrical principles: sensors (free nerve endings), wires (axons/nerves) and the perceptron (spinal cord & brain). Pain was described as either nociceptive (normal functioning of pain fibers), neuropathic (misfiring of axons/nerves), or central (dysfunctions of the central nervous system), the latter including the pain pathways in the spinal cord and the brain. In order to understand the underlying pathology causing pain, it is important to measure and quantify functioning of the pain nerve pathways.
Measuring pain is an ongoing goal of pain scientists. Recent reviews of some of these techniques, including PET, SPECT, fMRI and other neurometabolic and neurovascular tests, are discussed in Pain Imaging.2 These techniques, while useful in understanding the physiological effects of pain, are typically research tools and not readily available to the general practitioner.
This article will therefore limit specific discussion to one of those instruments that are both cost-effective for the general practitioner and have a solid background as an investigational tool — as demonstrated by a preponderance of peer-reviewed studies.3
The peripheral nervous system is composed of nerve fibers of varying diameters — some myelinated (insulated) and others non-myelinated — performing different functions in the body. Nerve fibers, intertwined in nerve bundles (see Figure 1), are differentiated as either motor nerves, sensory nerves, or autonomic nerves.
A schematic illustrating the differentiation and functionality of various types of nerves is presented in Figure 2.
The nerve fibers identified in the middle tier of Figure 2 are summarized as follows:
A-beta fibers are intermediate size, myelinated, and fastest sensory conductivity. These fibers mediate the sensation of touch, mild pressure, vibration, and joint positioning sensations. These are measured in the sensory nerve conduction tests of standard electrodiagnostic studies (EMG/NCV).
A-delta fibers are small, myelinated, and moderate sensory conductivity speed. These fibers mediate the sensation of cold and the secondary components of cold sensation and pain.
C-fibers are the smallest diameter, non-myelinated, and slowest sensory and motor conductivity. These fibers mediate the sensation of heat and the primary components of hot sensation and pain.
Clinical experience dictates that there are macroscopic populations of nociceptive nerve fibers throughout the body6 and individual axons within these populations must be dysfunctional to varying degrees — a range of normal functioning to nerve death (see Figure 3) in neuropathies.
Normal Nerve Function
Nerves are protoplasmic tubes or strands that conduct signals from a particular region of the body where the population of axons may be normal, irritated or basically dead. Such strands typically intertwine into a cable or bundle (see Figure 1), usually thought of as the nerve, and then feeds into the complex central nervous system (perceptron).
When the small A-delta and C-fibers function normally, the subject can feel temperature changes rather quickly and can also tolerate thermal pain over a significant temperature range.
The known response of normal A-delta and C-fiber nerves to temperature provides a useful benchmark against which measurements of potentially damaged nerves can be compared. The importance of characterizing whether a nerve is more active than normal or less active than normal is that we can characterize to some extent the amount of damage to these nerves.
Although measuring temperature response is not a direct measure of mechanical or chemical nerve pain or dysfunction, thermal measurements do, however, directly measure thermal pain nerve dysfunction. Because these different nerve types are coincidental in size and location, direct and useful deduction can be made for the other types (mechanical and chemical) pain nerve/axon types.
Nerve Changes Over Time
In reality, nerve/axon damage is subjected to gradients5 of insults over time and location. Trauma can cause tissue changes such as inflammation which, in turn, can damage nerves adjacent to the original trauma (or repetitive damage) site. These phenomena should be true for both the A-delta and C-fibers. It is fairly clear that not only does an axon and nerve evolve in degree and type of damage over time, but that a particular type of pain, from a pathway perspective (nociceptive, neuropathic, or central), can evolve into another type of pain or, alternately, involve another type of pain (see Figure 4).
Finally, it appears to the author that there may be cross-talk between these types of nerve fibers, resulting in an appropriate designation of Complex Regional Pain Syndrome.
Figure 5 presents a simple, conceptual model of nerve/axon dysfunction. The anatomical distribution of damage, as well as the degree, is variable in different individuals with different pain conditions over time. Such damage can have immediate
The distribution of damage is logically related to the direction and the character of mechanical and/or chemical insult to the nerve and axons. The mechanical insult can be acute traumatic or repetitive insults, such as rubbing, but is usually both acute and repetitive. The distribution of damage in nerves (nerve bundles) can be surface, regional, or diffuse.
The basic unit of damage is the axon, the single nerve fiber that extends from the nerve ending distally to the ganglia at the spinal cord proximally. The axon damage can be associated with A-delta fibers, C-fibers, or both. The degree, of course, is usually different depending on fiber type and varies over time. The degree of damage can be characterized as normal function, hyperactivity (such as irritation) and/or hypoactivity, and, ultimately, nerve death (see Figure 3).
Mixed Damage in Axon Populations
In the infinite possible mixtures of damage characteristics in nerves, we can easily project that — in pure nociceptive pain — all of the axons of both A-delta and C-fibers are functioning normally. We can also theoretically project that there could be a proportion of irritated and dead axons that would still result in perceived normal activity of the nerve.
If all the pain axons were dead, there would be no transmission of pain signals. If all the pain axons were irritated, the afflicted individual would likely have unbearable pain. Table 1 illustrates a mixed population of damaged and normal axons that exhibits normal function over-all. This phenomena has been clinically observed by the author among pain patients.