key linkage between pain and a specific brain molecule,

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-- ScienceDaily (Mar. 13, 2008) — Researchers at the University of Michigan

Health System have found a key linkage between pain and a specific brain

molecule, a discovery that lends new insight into fibromyalgia, an

often-baffling chronic pain condition.

In patients with fibromyalgia, researchers found, pain decreased when levels

of the brain molecule called glutamate went down. The results of this study,

which appears in the journal Arthritis and Rheumatism, could be useful to

researchers looking for new drugs that treat fibromyalgia, the authors say.

" If these findings are replicated, investigators performing clinical

treatment trials in fibromyalgia could potentially use glutamate as a

'surrogate' marker of disease response, " says lead author E. ,

Ph.D., research assistant professor in the Division of Rheumatology at the

U-M Medical School's Department of Internal Medicine and a researcher at the

U-M Chronic Pain and Fatigue Research Center.

The molecule glutamate is a neurotransmitter, which means it conveys

information between neurons in the nervous system. When glutamate is

released from one neuron, it diffuses across the space between cells, and

then binds to receptors on the next neuron in line and causes the cell to

become excited, or to be more active.

This molecule was suspected to play a role in fibromyalgia because previous

studies had shown that some brain regions in fibromyalgia patients appear to

be highly excited. One such region is the insula.

In functional magnetic resonance imaging (fMRI) studies, researchers at U-M

had previously shown that the insula displays augmented activity in

fibromyalgia, which means neurons in these patients are more active in this

part of the brain. The U-M team hypothesized, notes, 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 a

non-invasive brain imaging techinique called proton magnetic resonance

spectroscopy (H-MRS). H-MRS was performed once before and once following a

four-week course of acupuncture or " sham " acupuncture.

Researchers used either acupuncture or sham acupuncture to reduce pain

symptoms. The sham procedure involved using a sharp device to prick the skin

in order to mimic real acupuncture sensations.

Following the four weeks of treatment, both clinical and experimental pain

reported were reduced significantly. More importantly the reduction in both

pain outcomes was linked with reductions in glutamate levels in the insula:

patients with greater reductions in pain showed greater reductions in

glutamate. This suggests that glutamate may play a role in this disease and

that it could potentially be used as a biomarker of disease severity.

Because of the small number of participants in this study, further research

should be conducted to verify the role of glutamate in fibromyalgia,

says.

The senior author of the study was J. Clauw, M.D., director of the

U-M Chronic Pain and Fatigue Research Center. Other authors were H.

Gracely, Ph.D., and Seong-Ho Kim, M.D., of the U-M Department of Internal

Medicine; Pia C. Sundgren, M.D., Ph.D., Yuxi Pang, Ph.D., and Myria Petrou,

M.D., of the U-M Department of Radiology; Hsu, M.D., of the U-M

Department of Physical Medicine and Rehabilitation; and A. McLean,

M.D., of the U-M Department of Emergency Medicine.

Funding came from a Department of Army grant, the National Institutes of

Health, and the NIH National Center for Complementary and Alternative

Medicine.

Reference: Arthritis and Rheumatism, March 2008, Volume 58, Issue 3,

" Dynamic Levels of Glutamate within the Insula are Associated with

Improvements in Multiple Pain Domains in Fibromyalgia. "

Adapted from materials provided by University of Michigan Health System.

http://www.sciencedaily.com/releases/2008/03/080310112658.htm

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