Brief Report: Excitatory and Inhibitory Brain Metabolites as Targets of Motor Cortex Transcranial Direct Current Stimulation Therapy and Predictors of Its Efficacy in Fibromyalgia
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OBJECTIVE: Transcranial direct current stimulation (tDCS) has been shown to improve pain symptoms in fibromyalgia (FM), a central pain syndrome whose underlying mechanisms are not well understood. This study was undertaken to explore the neurochemical action of tDCS in the brain of patients with FM, using proton magnetic resonance spectroscopy (1H-MRS). METHODS: Twelve patients with FM underwent sham tDCS over the left motor cortex (anode placement) and contralateral supraorbital cortex (cathode placement) for 5 consecutive days, followed by a 7-day washout period and then active tDCS for 5 consecutive days. Clinical pain assessment and 1H-MRS testing were performed at baseline, the week following the sham tDCS trial, and the week following the active tDCS trial. RESULTS: Clinical pain scores decreased significantly between the baseline and active tDCS time points (P = 0.04). Levels of glutamate + glutamine (Glx) in the anterior cingulate were significantly lower at the post–active tDCS assessment compared with the post–sham tDCS assessment (P = 0.013), and the decrease in Glx levels in the thalami between these time points approached significance (P = 0.056). From baseline to the post–sham tDCS assessment, levels of N-acetylaspartate (NAA) in the posterior insula increased significantly (P = 0.015). There was a trend toward increased levels of γ-aminobutyric acid (GABA) in the anterior insula after active tDCS, compared with baseline (P = 0.064). Baseline anterior cingulate Glx levels correlated significantly with changes in pain score, both for the time period from baseline to sham tDCS (β1 = 1.31, P < 0.001) and for the time period from baseline to active tDCS (β1= 1.87, P < 0.001). CONCLUSION: The present findings suggest that GABA, Glx, and NAA play an important role in the pathophysiology of FM and its modulation by tDCS.
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The model fits data about the presence of GABA-glutamate unbalance and the finding of glutamic acid decarboxylase decrease in FM patients.
“Second, it fits data about the presence of GABA-glutamate unbalance [136–138], and the finding of glutamic acid decarboxylase decrease in FM patients [139].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [136]
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- Authors
- Foerster, B. R., Nascimento, T. D., DeBoer, M., Bender, M. A., Rice, I. C., Truong, D. Q., Bikson, M., Clauw, D. J., Zubieta, J., Harris, R. E., & DaSilva, A. F.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- DaSilva, Alexandre F.
- ORCID
- Venue
- Arthritis & Rheumatology
- Publisher
- Wiley
- Published
- 2015-01-28
- Volume
- 67
- Issue
- 2
- Pages
- 576-581
- ISSN
- 2326-5191 (ISSN-L)
- 2326-5205
- PMC
- PMC4446981
- OpenAlex
- W2156551648
- Cited by
- 105
- References
- 24
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 4 · 2023: 11 · 2022: 13 · 2021: 8 · 2020: 12 · 2019: 6 · 2018: 7 · 2017: 9 · 2016: 18 · 2015: 6
- FWCI
- 5.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arthritis & Rheumatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- This study was funded by a MICHR Clinical Trial Planning Program and CTSA high-tech funding grant, University of Michigan. (U039842)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- fibromyalgia, transcranial direct current stimulation, motor cortex stimulation, glutamate/glutamine, N-acetylaspartate, GABA, anterior cingulate cortex, thalamus, posterior insula, anterior insula, brain metabolites, central pain, pain modulation, 1H NMR
- MeSH terms
- Adult, Aspartic Acid, Brain, Female, Fibromyalgia, gamma-Aminobutyric Acid, Glutamine, Humans, Longitudinal Studies, Middle Aged, Motor Cortex, Pain Measurement, Treatment Outcome, Glutamic Acid, Transcranial Direct Current Stimulation, Proton Magnetic Resonance Spectroscopy
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