Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia


Edición | Fibromialgia.nom.es 10-07-2008

Richard E. Harris * , Pia C. Sundgren, Yuxi Pang, Michael Hsu, Myria Petrou, Seong-Ho Kim, Samuel A. McLean, Richard H. Gracely, Daniel J. Clauw

University of Michigan, Ann Arbor

email: Richard E. Harris ( reharris@med.umich.edu )

* Correspondence to Richard E. Harris, University of Michigan, Chronic Pain and Fatigue Research Center, 24 Frank Lloyd Wright Drive, PO Box 385, Lobby M, Ann Arbor, MI 48106

ClinicalTrials.gov identifier: NCT00142597.
Dr. Harris has received consulting fees from Pfizer as part of an investigator-initiated study of acupuncture in fibromyalgia and has received speaking fees (less than $10,000) from the University of North Carolina Pelvic Pain Conference. Dr. Clauw has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Wyeth and (more than $10,000 each) from Eli Lilly, Pfizer, Cypress Bioscience, and Forest Laboratories.

Funded by:
 US Department of Army; Grant Number: DAMD-17/002-0018, DAMD award W81XW94-07-2-0050
 NIH/National Center for Research Resources; Grant Number: M01-RR-000042
 NIH/National Center for Complementary and Alternative Medicine; Grant Number: K01-AT-01111-01
 NIH; Grant Number: K12-RR-017607-01


Fibromyalgia (FM) is a chronic widespread pain condition that is thought to arise from augmentation of central neural activity. Glutamate (Glu) is an excitatory neurotransmitter that functions in pain-processing pathways. This study was carried out to investigate the relationship between changing levels of Glu within the insula and changes in multiple pain domains in patients with FM.


Ten patients with FM underwent 2 sessions of proton magnetic resonance spectroscopy (H-MRS) and 2 sessions of functional magnetic resonance imaging (FMRI), each conducted before and after a nonpharmacologic intervention to reduce pain. During H-MRS, the anterior and posterior insular regions were examined separately using single-voxel spectroscopy. The levels of Glu and other metabolites were estimated relative to levels of creatine (Cr) (e.g., the Glu/Cr ratio). During FMRI, painful pressures were applied to the thumbnail to elicit neuronal activation. Experimental pressure-evoked pain thresholds and clinical pain ratings (on the Short Form of the McGill Pain Questionnaire [SF-MPQ]) were also assessed prior to each imaging session


Both experimental pain ( P = 0.047 versus pretreatment) and SF-MPQ-rated clinical pain ( P = 0.043 versus pretreatment) were reduced following treatment. Changes from pre- to posttreatment in Glu/Cr were negatively correlated with changes in experimental pain thresholds (r = -0.95, P < 0.001) and positively correlated with changes in clinical pain (r = 0.85, P = 0.002). Changes in the FMRI-determined blood oxygenation level-dependent effect (a measure of neural activation) were positively correlated with changes in Glu/Cr within the contralateral insula (r = 0.81, P = 0.002).


Changes in Glu levels within the insula are associated with changes in multiple pain domains in patients with FM. Thus, H-MRS data may serve as a useful biomarker and surrogate end point for clinical trials of FM.


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