Proton MRS links fibromyalgia pain to changes in brain molecule

April 10, 2008

Widespread muscle and tissue pain, tenderness, and fatigue are well-documented symptoms of fibromyalgia, a chronic condition that affects up to an estimated 6% of the U.S. population. The underlying pathology of the pain disease is unknown. A new study featuring proton MR spectroscopy, however, has found a key linkage between the pain and a specific brain molecule.

Widespread muscle and tissue pain, tenderness, and fatigue are well-documented symptoms of fibromyalgia, a chronic condition that affects up to an estimated 6% of the U.S. population. The underlying pathology of the pain disease is unknown. A new study featuring proton MR spectroscopy, however, has found a key linkage between the pain and a specific brain molecule.

Researchers at the University of Michigan Health System found pain in patients with fibromyalgia decreased when levels of glutamate went down. The main strength of the study was a novel approach using proton MR spectroscopy (H1-MRS) to obtain insight into brain metabolism.

"No one has used the intervention that we used,'' said lead author Richard E. Harris, Ph.D., a research assistant professor in the rheumatology division of the U-M Medical School's internal medicine department. "It gives you an idea of a specific molecule in the brain being involved in a pathology of the disease, and that's information we didn't have before."

The results of the study, published in Arthritis and Rheumatism, could be useful to researchers looking for new drugs that treat fibromyalgia. Dr. Daniel J. Clauw, director of the U-M Chronic Pain and Fatigue Research Center, was senior author of the study.

"It's possible that specialists might be able to use glutamate as a biomarker for this condition for clinical research purposes," Harris said. "Glutamate might be able to be combined with PET or functional MRI, where you use the level of neurotransmitter concentration in individuals as a covariate of other imaging results."

Glutamate was suspected to play a role in fibromyalgia because previous studies had shown that some brain regions, particularly the insula, appear to be highly excited. In previous fMRI studies, researchers had shown that the insula displays augmented activity in fibromyalgia. Harris's team hypothesized that more activity among these neurons might be related to the level of glutamate in this region.

To gauge the linkage between pain and glutamate, the researchers used H1-MRS on 21 patients with fibromyalgia and 27 healthy controls. The use of 2D chemical shift imaging H1-MRS, as opposed to single-voxel methods, allowed the team to simultaneously assess a greater number of brain regions, the report said.

H1-MRS was performed once before and once following a four-week course of acupuncture or "sham" acupuncture to reduce pain symptoms. Following the four weeks of treatment, patients reported reductions in both clinical and experimental pain.

The outcome was linked with reductions in glutamate levels in the insula: Patients with greater reductions in pain showed greater reductions in glutamate.

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