Pathophysiology Associated With Fibromyalgia

Marilyn W. Edmunds, PhD, CRNP; Laurie E. Scudder, MS, NP


August 28, 2009

Changes in Gray Matter Density in Fibromyalgia: Correlation With Dopamine Metabolism

Wood PB, Glabus MF, Simpson R, Patterson JC 2nd
J Pain. 2009;10:609-618

Article Summary

Careful research has demonstrated that fibromyalgia (FM) is a clinical problem that involves much more than pain. The disorder is now increasingly recognized to involve cognitive dysfunction, which is variously characterized by difficulty with short-term recall (working memory), difficulty encoding new information when distracted (multitasking), and slowed speed of mental processing and word-finding. In addition to pain and cognitive symptoms, perceptual disturbances are also recognized, including disturbance in the ability to make figure/ground distinctions, loss of depth perception, and an inability to focus vision and attention. The symptom range of fibromyalgia compels us to pay more attention to this problem with the hope that increased knowledge will lead to better treatment strategies.

Fibromyalgia has been found to be associated with alterations in brain morphometry and abnormal dopaminergic neurotransmission. Evidence from preclinical models has demonstrated that dopamine plays a role in promoting neuronal integrity. This study was designed to (1) confirm previous findings of reduced gray matter density in subjects with FM; and (2) determine whether variations in dopamine metabolism might affect the density of gray matter in affected individuals.

The sample included 30 women with fibromyalgia and 20 age- and gender-matched healthy control subjects. Voxel-based morphometry was used to evaluate anatomic magnetic resonance imaging data in both groups. In addition, data from a subset of subjects from both groups who had previously participated in a positron emission tomography study using radiolabeled dihydroxyphenylalanine (n = 14; 6 FM subjects and 8 control subjects) were used to determine whether a correlation might exist between gray matter density and dopamine metabolism.

The study revealed that in patients with FM, there was a significant reduction in gray matter density within specific parts of the brain: the bilateral parahippocampal gyri, the right posterior cingulate cortex, and the left anterior cingulate cortex. In addition, a positive correlation was demonstrated between gray matter density of the bilateral hippocampal gyri and left pregenual cortex and an index of dopamine metabolism from the ventral tegmental area where cell bodies of corticolimbic projection neurons originate. These results confirm previous findings that FM is associated with altered brain morphometry. Alterations in dopamine metabolism might contribute to the associated changes in gray matter density.

Fibromyalgia was found to be associated with reductions in gray matter density within brain regions that are likely involved in phenomena related to the disorder. These phenomena include enhanced pain perception, cognitive dysfunction, and abnormal stress reactivity. The authors report that given the growing evidence of abnormal dopaminergic neurotransmission associated with FM, the strong correlation between dopamine metabolism and gray matter density seems to suggest the pathophysiology that might contribute to these changes.


This is a technically sophisticated but clinically interesting study. I find these results fascinating given that so many patients with fibromyalgia must struggle for years to have someone accept that the symptoms they have with fibromyalgia are not (figuratively) "all in their head." Although this study is so technical that it will not be of interest to all clinicians, it may be worth keeping in your files to remind you periodically that just because we can't explain someone's symptoms, it doesn't mean they are not real. It may just take time and research to uncover the true nature of the problem, and each study like this one adds another piece to the puzzle.



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