Elevated insular glutamate in fibromyalgia is associated with experimental pain
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OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
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The pathophysiology of fibromyalgia syndrome seems to be related to sensitization of central nervous system processes, which underlie alterations in pain perception, deficient pain inhibition, temporal summation of pain, and other indicators of pain sensitization.
“Regarding the etiopathophysiology of FMS, while its etiology remains unknown, the pathophysiology of this chronic condition seems to be related to the sensitization of CNS processes, e.g., [5,22,23], which underlie the alterations in pain perception displayed by these patients, (e.g., allodynia and hyperalgesia) [24], deficient pain inhibition [25], temporal summation of pain [26] and other”
From Effectiveness of acceptance and commitment therapy in central pain sensitization syndromes: A systematic review (2021) · cites this paper as [23]
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- Authors
- Harris, R. E., Sundgren, P. C., Craig, A. D., Kirshenbaum, E., Sen, A., Napadow, V., & Clauw, D. J.
- Affiliations
- University of Michigan (US)
- Barrow Neurological Institute (US)
- Massachusetts General Hospital (US)
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2009-09-29
- Volume
- 60
- Issue
- 10
- Pages
- 3146-3152
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- PMC
- PMC2827610
- OpenAlex
- W2032867586
- Cited by
- 328
- References
- 31
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 9 · 2023: 20 · 2022: 20 · 2021: 20 · 2020: 23 · 2019: 21 · 2018: 17 · 2017: 26 · 2016: 22 · 2015: 15 · 2014: 20 · 2013: 20 · 2012: 19
- FWCI
- 12.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Center for Research Resources (M01RR000042)
- National Center for Complementary and Integrative Health (K01-AT-01111-01, R01AT004714, K01AT001111, K01-01-AT-002166, K01AT002166, P01AT002048)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- fibromyalgia, insula, glutamate, glutamine, 1H NMR, pressure pain threshold, central sensitization, glutamatergic neurotransmission, anterior insula, posterior insula, functional pain syndromes
- MeSH terms
- Adult, Cerebral Cortex, Female, Fibromyalgia, Glutamine, Humans, Middle Aged, Magnetic Resonance Spectroscopy, Pain, Case-Control Studies, Pain Threshold, Glutamic Acid
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