Dr. Harris has received consulting fees, speaking fees, and/or honoraria from Pfizer (less than $10,000).
Elevated insular glutamate in fibromyalgia is associated with experimental pain†
Article first published online: 29 SEP 2009
Copyright © 2009 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 60, Issue 10, pages 3146–3152, October 2009
How to Cite
Harris, R. E., Sundgren, P. C., Craig, A. D., Kirshenbaum, E., Sen, A., Napadow, V. and Clauw, D. J. (2009), Elevated insular glutamate in fibromyalgia is associated with experimental pain. Arthritis & Rheumatism, 60: 3146–3152. doi: 10.1002/art.24849
ClinicalTrials.gov identifier: NCT00142597.
- Issue published online: 29 SEP 2009
- Article first published online: 29 SEP 2009
- Manuscript Accepted: 23 JUN 2009
- Manuscript Received: 31 MAR 2009
- US Department of the Army. Grant Number: DAMD-W81XWH-07-2-0050
- NIH (National Center for Research Resources grant. Grant Number: M01-RR-000042
- Dana Foundation (Award in Brain and Immuno-Imaging)
- NIH (National Center for Complementary and Alternative Medicine grant. Grant Number: K01-AT-01111-01)
- NIH (National Center for Complementary and Alternative Medicine grants. Grant Numbers: K01-AT-002166, R01-AT-004714, P01-AT-002048)
Central pain augmentation resulting from enhanced excitatory and/or decreased inhibitory neurotransmission is a proposed mechanism underlying the pathophysiology of functional pain syndromes such as fibromyalgia (FM). Multiple functional magnetic resonance imaging studies implicate the insula as a region of heightened neuronal activity in this condition. Since glutamate (Glu) is a major cortical excitatory neurotransmitter that functions in pain neurotransmission, we undertook this study to test our hypothesis that increased levels of insular Glu would be present in FM patients and that the concentration of this molecule would be correlated with pain report.
Nineteen FM patients and 14 age- and sex-matched pain-free controls underwent pressure pain testing and a proton magnetic resonance spectroscopy session in which the right anterior insula and right posterior insula were examined at rest.
Compared with healthy controls, FM patients had significantly higher levels of Glu (mean ± SD 8.09 ± 0.72 arbitrary institutional units versus 6.86 ± 1.29 arbitrary institutional units; P = 0.009) and combined glutamine and Glu (i.e., Glx) (mean ± SD 12.38 ± 0.94 arbitrary institutional units versus 10.59 ± 1.48 arbitrary institutional units; P = 0.001) within the right posterior insula. No significant differences between groups were detected in any of the other major metabolites within this region (P > 0.05 for all comparisons), and no group differences were detected for any metabolite within the right anterior insula (P > 0.11 for all comparisons). Within the right posterior insula, higher levels of Glu and Glx were associated with lower pressure pain thresholds across both groups for medium pain (for Glu, r = −0.43, P = 0.012; for Glx, r = −0.50, P = 0.003).
Enhanced glutamatergic neurotransmission resulting from higher concentrations of Glu within the posterior insula may play a role in the pathophysiology of FM and other central pain augmentation syndromes.