Brief Report: Excitatory and Inhibitory Brain Metabolites as Targets of Motor Cortex Transcranial Direct Current Stimulation Therapy and Predictors of Its Efficacy in Fibromyalgia

Abstract

Objective Transcranial direct current stimulation (tDCS) has been shown to improve pain symptoms in fibromyalgia (FM), a central pain syndrome; the underlying mechanisms are not well understood. Our objective was to explore the neurochemical action of tDCS in the FM brain using proton magnetic resonance spectroscopy (1H-MRS). Methods Twelve patients with FM underwent sham tDCS over the left motor (anode) and contralateral supraorbital cortices (cathode) (M1-SO) for 5 consecutive days, a 7 day washout period, and then active M1-SO tDCS for 5 consecutive days. The subjects had clinical pain assessment and 1H-MRS testing at baseline, the week following post-sham tDCS trial, and the week following post-active tDCS trial. Results There was a significant decrease in clinical pain scores between baseline and active tDCS time-points (P=0.04). There was a significant decrease in Glx (glutamate and glutamine) in the anterior cingulate (P=0.013) and a trend towards decreased Glx in the thalami (P=0.056) for the sham-active tDCS comparison. For the baseline-sham tDCS comparison, there was a significant increase in N-acetylaspartate (NAA) levels in the posterior insula (P=0.015). There was a trend towards increased γ-aminobutyric acid (GABA) in the anterior insula for the baseline-active tDCS comparison (P=0.064). There were significant linear regression coefficients between anterior cingulate Glx levels at baseline and the clinical pain scale changes between the baseline-sham tDCS comparison (β1=1.31;P<0.001) and the baseline-active tDCS comparison (β1=1.87;P<0.001). Conclusion Our findings suggest that GABA, Glx and NAA play an important role in the pathophysiology of FM and its modulation by tDCS.

Sensorimotor and pain‐related alterations of the gray matter and white matter in Type 2 diabetic patients with peripheral neuropathy

“…Specifically, the ACC has been reported to be a pain‐intensity encoding region in both healthy volunteers and in animal models (Apkarian, Baliki, & Geha, ; Duerden & Albanese, ; Farrell, Laird, & Egan, ; Senapati et al, ). In addition, recent metabolic studies indicated that chronic knee osteoarthritis pain and fibromyalgia were associated with reduced levels of the inhibitory neurotransmitter GABA in the ACC, which was thought to reflect a disinhibition mechanism of this region in pain perception (Foerster et al, ; Reckziegel, Raschke, Cottam, & Auer, ). Further, the PFC has been shown to exert inhibitory control on the medial thalamus‐ACC loop (Cauda et al, ).…”

Neurobiology of fibromyalgia and chronic widespread pain

“…In addition to substance P, elevations in CNS glutamate levels in fibromyalgia, measured both in the CSF (Sarchielli et al, 2007) and directly in the brain using proton spectroscopy (H-MRS) are also found in individuals with fibromyalgia (Harris et al, 2009, Fayed et al, 2010, Harris, 2010). In fact, using proton magnetic resonance spectroscopy, glutamate levels in fibromyalgia patients are also elevated in key pain-processing areas of the brain such as the insula and change in response to changes in both clinical and experimental pain when patients are successfully treated (Harris et al, 2008, Harte et al, 2013, Foerster et al, 2015). For example, pregabalin decreases glutamatergic activity in the insula and decreases functional connectivity between the default mode network and insula in individuals with fibromyalgia (Harris et al, 2013).…”

A description and critical analysis of the therapeutic uses of transcranial direct current stimulation: implications for clinical practice and research

“…In a typical study, Foerster and colleagues administered tDCS to 12 patients with fibromylagia. 22 The dosage consisted of 2.0 mA with the anodal electrode placed over the left motor cortex (M1) and the cathodal electrode placed over the contralateral right supraorbital cortex (~Fp2) (Figure 2). Compared to the sham condition, when patients received the active tDCS treatment, a significant decrease was observed in clinical pain scores.…”