Pain Research and Treatment
Volume 2012 (2012), Article ID 585419, 8 pages doi:10.1155/2012/585419:
Neurobiology Underlying Fibromyalgia Symptoms
Marta Ceko,1,2 M. Catherine Bushnell,1,2,3 and Richard H. Gracely4
1Alan Edwards Centre for Research on Pain, McGill University, 3640 University Street, Room M19, Montreal, QC, H2A 1C1, Canada
2Department of Neurology & Neurosurgery, McGill University, 3640 University Street, Room M19, Montreal, QC, H2A 1C1, Canada
3Department of Anesthesia, McGill University, 3640 University Street, Room M19, Montreal, QC, H2A 1C1, Canada
4Center for Neurosensory Disorders, University of North Carolina, CB No. 7280, 3330 Thurston Building, Chapel Hill, NC 27599, USA
Received 27 April 2011; Accepted 23 August 2011
Academic Editor: Muhammad B. Yunus
Copyright © 2012 Marta Ceko et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Fibromyalgia is characterized by chronic widespread pain, clinical symptoms that include cognitive and sleep disturbances, and other abnormalities such as increased sensitivity to painful stimuli, increased sensitivity to multiple sensory modalities, and altered pain modulatory mechanisms. Here we relate experimental findings of fibromyalgia symptoms to anatomical and functional brain changes. Neuroimaging studies show augmented sensory processing in pain-related areas, which, together with gray matter decreases and neurochemical abnormalities in areas related to pain modulation, supports the psychophysical evidence of altered pain perception and inhibition. Gray matter decreases in areas related to emotional decision making and working memory suggest that cognitive disturbances could be related to brain alterations. Altered levels of neurotransmitters involved in sleep regulation link disordered sleep to neurochemical abnormalities. Thus, current evidence supports the view that at least some fibromyalgia symptoms are associated with brain dysfunctions or alterations, giving the long-held “it is all in your head” view of the disorder a new meaning.
3.4. What Do the Psychophysical, Cognitive, and Neuroimaging Studies Tell Us about the Neurobiology Underlying FM Symptoms?
The wealth of experimental evidence showing that FM patients are hypersensitive to painful stimuli, as well as unpleasant stimuli from other sensory modalities, in conjunction with functional brain imaging data showing increased stimulus-evoked activation throughout nociceptive pathways, shows that the defining symptom of FM—increased pain—is in fact real and not just a response bias of the patients. The finding that perception is increased in multiple modalities speaks against the hypothesis that FM pain is due to an upregulation of peripheral nociceptive processes. Further, psychophysical evidence that descending modulatory systems are altered in FM patients supports the opposing idea that FM symptoms are at least in part caused by alterations in CNS processing of the pain signal, including a dysregulation of pain modulatory systems. Nevertheless, the apparent dysregulation within these systems could be caused and/or perpetuated by a tonic activation related to the presence of ongoing widespread pain, so that the systems are saturated and cannot regulate further in response to external stimuli.
Since similar descending control systems, including attentional and emotional regulatory circuitry, affect multiple sensory modalities [113–119], a dysfunction (or saturation) in these systems could lead to the hypersensitivity in multiple sensory modalities. FM patients show reduced habituation to nonpainful tactile stimuli and increased cortical response to intense auditory stimuli, both of which have been linked to deficient inhibition of incoming sensory stimuli [120, 121]. Also in support of the idea of a central dysregulation or saturation of pain modulation are changes in the opioid and dopamine neurotransmitter systems, both known to be involved in hedonic regulation .
Finally, the findings that FM patients not only perceive themselves to have altered memory and concentration (“fibrofog”), but also in fact perform poorly on multiple cognitive tests, even when depression is excluded as a contributing factor, suggest that there are alterations in brain function. The anatomical brain imaging studies that show reductions in gray matter in frontal regions important for cognitive function further indicate that this common symptom of FM is based on altered brain function. Together, the experimental evidence provides strong support for the idea that FM symptoms are related to dysfunctions in the central nervous system. The cause of these changes cannot be deduced from the available evidence, as it is correlational in nature. Did long-term ongoing pain cause the changes or did the changes cause the pain? Without a relevant animal model or long-term longitudinal studies, we cannot answer these questions. Nevertheless, we can at least say that fibromyalgia is real and that it is associated with multiple changes in the brain.