• Arthritis and rheumatism · Mar 2008

    Randomized Controlled Trial

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

    • Richard E Harris, Pia C Sundgren, Yuxi Pang, Michael Hsu, Myria Petrou, Seong-Ho Kim, Samuel A McLean, Richard H Gracely, and Daniel J Clauw.
    • University of Michigan, Chronic Pain and Fatigue Research Center, Ann Arbor, MI 48106, USA. reharris@med.umich.edu
    • Arthritis Rheum. 2008 Mar 1;58(3):903-7.

    ObjectiveFibromyalgia (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.MethodsTen 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 sessionResultsBoth 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).ConclusionChanges 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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