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Last updated: Fri, Feb 28, 2025
This page presents findings about how the functioning of the pain matrix is different in chronic pain patients.
Studies have been done on the pain matrix of CPPs. Some studies have looked at the unprovoked ("spontaneous") variability in pain, while other studies have deliberately provoked pain of the quality that is usual for a specific chronic pain condition. (For example, mechanical allodynia has been provoked among sufferers of neuropathies. See Neuropathy and Neuralgia.)
Another type of study has compared the reaction of CPPs to that of normals to controlled painful stimuli. These have been done primarily with CPPs suffering from irritable bowel syndrome, fibromyalgia, and vulvovestibulitis. (This excludes sufferers of myofascial or neuropathic pains.) In comparison with normals, brain activations in CPPs are elevated to pain stimuli of the same intensity (for example, the same heat for the same duration). This demonstrates that the nociceptive signals reaching the brain are elevated, but doesn't tell us why or where this occurs. The activation of the pain matrix corresponds to perceived pain intensity in the same way for both normals and CPPs. This supports the idea that this class of CPPs is in fact more pain-sensitive than normals.1
Several generalized findings have been made about the pain matrix under chronic pain conditions.2
(1) The primary and secondary somatosensory cortices (S1 and S2) have been less activated in chronic pain. These are the areas most likely responsible for sensory discriminations: location, intensity, and duration. (Functions of the Pain Matrix.)
(2) Brain activation has been found to differ depending on the trajectory of the pain. When pain increases rapidly, activation for CPPs is very similar to that for normals when they are subjected to acute experimental pain. During periods of sustained high pain, however, the amygdala and PFC were activated. Certain brain stem areas were also differentially activated during sustained high pain.
Increased activation of the PFC during sustained high pain in CPPs could reflect more intense appraisal activities, including consulting memory banks, among the CPPs. Both the PFC and the amygdala are involved in descending pain modulation, and it is possible that this elevated activity may reflect or result in alterations in the pain modulation system. The amygdala is highly associated with emotion or affect, so its elevated activity may reflect or result in increased emotional arousal. Either of these could explain elevated activity in the brain stem.
(3) Activity in the thalamus is reduced in CPPs. Abnormal activity in the thalamus has been observed in a number of chronic pain conditions, in which normal response to afferent messages is reduced and "burst" discharges occur. Accompanying this, areas of the thalamus have been observed to have reduced blood flow. These conditions seem to resolve if the pain condition is resolved.
One study subjected non-patients (“normals”), chronic back pain patients ("CBPs"), and headache sufferers to controlled electrical stimulation of the finger. The back pain patients reported pain at a lower level of electrical stimulation than did the normals and headache sufferers. The back patients stopped escalation of stimulation at a lower level than the other two groups, and showed less habituation to the stimulation. The three groups showed equally high levels of brain activity as measured by EEG. This suggests central sensitization among the CBP patients.3 (In this experiment, CBPs reported higher levels of pain at the same level of brain activity.)
In another study, electrical stimulation was applied either to the back or to a finger of chronic back pain patients and non-patients. Brain activity was observed using MEG. Early activity in the primary somatosensory cortex was greater for the back patients than for the normals when the back was stimulated, but it was not higher when the finger was stimulated. The reaction of the brain to stimulation of the back was highest for those patients who had suffered from back pain the longest. When the back was stimulated, the location in the brain from which the main signal came was lower and more central than in the normals, and the magnetic signal level was higher. This suggests that the area in the somatosensory cortex that represents the back had expanded in the back pain patients.4 This is consistent with somatosensory expansions that are observed with other types of behaviorally relevant information. For example, piano players tend to devote a larger area of S1 to their fingers than people in general do.
A 2004 study tested CBP patients, FMS patients, and normals by applying measured pressure to their thumbnails. (Sounds like a torture chamber, right?) These subjects were observed using fMRI. The two types of patients (CBP and FMS) showed the same pattern of brain activation when subjected to the same amount of pressure. This pressure activated the primary somatosensory cortex (S1) on the side opposite the thumb, the secondary somatosensory cortex (S2) on both sides, the inferior parietal lobule, and the cerebellum. This same pressure applied to normal subjects activated S2 only on the side opposite the thumb. When subjects were subjected to pressure that produced the same levels of pain (as reported by the subjects), all groups showed activation of the same set of brain areas, but the magnitude of activation was greater for the two groups of patients than for the normals.5 (The pain network of the patients was more active at the same level of reported pain.)
A 2008 study observed CBP patients while in an fMRI machine. The patients were given a hand-held control which they could use to register the level of their pain as it spontaneously changed. Activation of the medial prefrontal cortex and the nucleus accumbens varied along with the reported pain level. Since these structures are associated with emotion, the researchers concluded that the spontaneous variations experienced by the CBP patients were of an emotional nature, that is, that they involved the “affective dimension” of pain experience.6
The patterns of brain activation seen in chronic pain patients are similar to the patterns seen in normal subjects who are exposed to brief experimental stimuli. Increased activation of the prefrontal cortex (PFC) and the amygdala are frequently seen in studies of chronic pain patients. High activity in the PFC could indicate increased activity in facilitatory or inhibitory descending circuits, depending on exactly which parts of the PFC are involved. High activity in the amygdala probably reflects the involvement of arousal or emotion in the pain process.7
In a 2006 study of patients with irritable bowel syndrome, researchers observed their subjects using brain imaging while stimulating the esophagus, apparently stretching it with a controlled-pressure bladder. They found that activation in the pain network increased even at levels of pressure that the subjects couldn't perceive. The reviewer notes that this suggests that at least part of the amplification [of pain] is related to non-psychological factors.
8 (Would this be because we don't have emotions about things that are outside of our conscious awareness? Yet pain is an emotion?? This interpretation seems fanciful to me.)
This study showed that activation of the pain matrix can occur even when the stimuli does not provoke pain that the subject is consciously aware of.9 This finding raises a question as to what the significance is of conscious awareness of pain. Or, looking at this another way, how ought pain science to treat situations in which the pain matrix is activated but the conscious awareness of pain is lacking? Does subliminal pain exist?
We saw in the section on fibromyalgia (Fibromyalgia, Whiplash, and Myofascial Pain (+CWP)) that FMS is now seen as a condition of central nervous system sensitization. A number of investigations have been made of other clinical syndromes to look at the role that central sensitization may play in them.
A study of patients with painful osteoarthritis of the hip observed the brain while the subjects were stimulated by punctate (point) stimuli. The patients felt the stimulus was sharper when it was applied to the side of the affected thigh. This is an area whose signals converge in the spine with signals from the hip joint. Elevated activity was seen in the ACC, the dorsolateral PFC, and the PAG. In these patients, the magnitude of activation of the periaqueductal gray (PAG), which is part of the descending modulatory system, was proportional to the patient's degree of central sensitization, as measured by responses to an instrument called PainDETECT.10 (See Central Sensitization.)
These experiments all report differences in the response of the central nervous system to controlled experimental stimulation between normals and chronic pain sufferers. Although the situations are different and details of the results are different, the experiments seem clearly to support the idea that chronic pain sufferers react differently to stimulation than normals do. The results also illustrate that there is much left to understand. As an example, it makes sense to wonder whether these differences are the result of the chronic pain conditions and whether they might be a cause or contributing factor for the conditions.
I called out in one of the paragraphs above that the interpretation of one of the experiments seemed "fanciful" to me. We all have an inclination, scientists included, to let our knowledge expand to fill any vacuums that we see in our narrative of these or other issues we're concerned about. I read the following in Handbook of Pain Assessment:
...tissue damage and associated nociception can produce sensitization of the peripheral nervous system and the central nervous system, and that this sensitization can subserve dissociation between tissue injury and pain.11
To "dissociate" means to separate or sever a connection. The evidence that I have read indicates that sensitization and other CNS pain phenomena can change the relationship between stimulation and sensation, affecting intensity, quality, location, and timing, but in ways that are characteristic, not dissociative. Although pain without tissue injury is known to occur, it is known best in connection with neuropathy, not sensitization. The quote above is true if just one instance can be found in which sensitization has "subserved" dissociation (whatever that may mean), and in that sense the statement says so little that it is hardly worth making. However, the statement implies a much broader phenomenon of dissociation by sensitization that isn't scientifically supportable. The quote comes from the chapter titled Assessment of Patients with Chronic Pain: A Comprehensive Approach,
which addresses evaluation of pain patients in the context of adversarial proceedings such as workers' compensation or disability.