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

Authors

  • Richard E. Harris,

    Corresponding author
    1. University of Michigan, Ann Arbor
    • University of Michigan, Chronic Pain and Fatigue Research Center, 24 Frank Lloyd Wright Drive, PO Box 385, Lobby M, Ann Arbor, MI 48106
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    • 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.

  • Pia C. Sundgren,

    1. University of Michigan, Ann Arbor
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  • Yuxi Pang,

    1. University of Michigan, Ann Arbor
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  • Michael Hsu,

    1. University of Michigan, Ann Arbor
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  • Myria Petrou,

    1. University of Michigan, Ann Arbor
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  • Seong-Ho Kim,

    1. University of Michigan, Ann Arbor
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  • Samuel A. McLean,

    1. University of Michigan, Ann Arbor
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  • Richard H. Gracely,

    1. University of Michigan, Ann Arbor
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  • Daniel J. Clauw

    1. University of Michigan, Ann Arbor
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    • 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.


  • ClinicalTrials.gov identifier: NCT00142597.

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.

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