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Summer 2002

Brain Abnormalities and CFS Pain

Several investigators have attempted to identify abnormalities in brain structures that might contribute to the painful symptoms of CFS. Their studies have focused on magnetic resonance imaging (MRI) of brain structure and neuroimaging of regional cerebral blood flow (rCBF) in brain structures that process or modulate pain.

MRI studies of brain structure.
The results of these studies are difficult to interpret because they are characterized by great variation in research methods that can influence the validity of research findings.³¹ Nevertheless, three of four relatively well-designed studies have reported CFS patients, compared to healthy controls, display a significantly greater number of white matter lesions in the cortex of the brain.^32-34 The relationship between these lesions and pain in persons with CFS remains unclear.

Neuroimaging of functional brain activity.
Single photon emission computed tomography (SPECT), positron emission tomography (PET) and functional MRI (fMRI) allow investigators to measure activity in brain structures either during rest or during exposure to stimuli that evoke acute pain. All of the peer-reviewed neuroimaging studies performed to date with CFS patients have examined brain activity during rest.^35-38 Six investigations have reported that CFS patients are characterized by low levels of rCBF in numerous brain structures.

There is little agreement regarding the specific brain structures that show low rCBF. Nevertheless, two investigations found that CFS patients, relative to controls, show significantly lower levels of rCBF in the brainstem.^36,37 Low brainstem rCBF levels may contribute to abnormal function of the locus ceruleus-norepinephrine/autonomic nervous system in CFS patients. This abnormality, in turn, may contribute to pain since the locus ceruleus is involved in controlling descending pathways from the brain to the spinal cord that inhibit pain.¹⁴

It should be noted, however, that Lewis and colleagues³⁸ recently used SPECT imaging to compare brain rCBF in 22 identical twin pairs in which only one twin met criteria for CFS. There was no difference in the number of brain rCBF abnormalities between twins with CFS and those without the disorder. At present, then, it is not possible to state with confidence whether a relatively large number of resting state abnormalities in brain function are found in persons with CFS, or whether any abnormalities that are found may contribute to persistent pain in persons with CFS.

Despite the inconsistent findings described above, it may be possible to better understand the causes of painful symptoms in CFS by measuring changes in brain rCBF that are produced by noxious stimulation (e.g., pressure, heat, or cold) in persons with CFS and healthy individuals. We recently completed brain SPECT imaging on nine patients with CFS who did not meet criteria for FM and 25 healthy controls.³⁹ Preliminary analyses indicate that, despite the fact that all of the CFS patients reported experiencing musculoskeletal pain, their pain thresholds for pressure stimulation did not differ from those of the healthy controls.

However, the CFS patients tended to show a different pattern of brain activation than the healthy controls when they were exposed to a five-minute period of repetitive, painful, pressure stimulation. That is, the controls showed the expected pattern of increased activity in brain structures involved in processing the sensory and emotional dimensions of pain located in the cerebral hemisphere opposite to the stimulation site (e.g., right-side stimulation evoked left brain activation). Interestingly, the CFS patients tended to show activation in the same structures in both cerebral hemispheres, despite the fact that there was no difference in the intensity of pressure stimulation delivered to patients and controls. This suggests that the pressure stimulation produced greater transmission of sensory input to the brains of the patients with CFS.