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Randomized Controlled Trial
. 2008 Mar;58(3):903-7.
doi: 10.1002/art.23223.

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

Richard E Harris  1 , Pia C Sundgren, Yuxi Pang, Michael Hsu, Myria Petrou, Seong-Ho Kim, Samuel A McLean, Richard H Gracely, Daniel J Clauw
Affiliations
Free article
Randomized Controlled Trial

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

Richard E Harris et al. Arthritis Rheum. 2008 Mar.
Free article

Abstract

Objective: 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.

Methods: 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

Results: 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).

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00142597.

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