Reduced insular γ-aminobutyric acid in fibromyalgia

Abstract

Objective: Recent scientific findings have reinvigorated interest in examining the role of γ-aminobutyric acid (GABA), the major inhibitory central nervous system neurotransmitter, in chronic pain conditions. Decreased inhibitory neurotransmission is a proposed mechanism in the pathophysiology of chronic pain syndromes such as fibromyalgia (FM). The purpose of this study was to test the hypothesis that decreased levels of insular and anterior cingulate GABA would be present in FM patients, and that the concentration of this neurotransmitter would be correlated with pressure-pain thresholds.

Methods: Sixteen FM patients and 17 age- and sex-matched healthy controls underwent pressure-pain testing and a 3T proton magnetic resonance spectroscopy session in which the right anterior insula, right posterior insula, anterior cingulate, and occipital cortex were examined in subjects at rest.

Results: GABA levels in the right anterior insula were significantly lower in FM patients compared with healthy controls (mean ± SD 1.17 ± 0.24 arbitrary institutional units versus 1.42 ± 0.32 arbitrary institutional units; P = 0.016). There was a trend toward increased GABA levels in the anterior cingulate of FM patients compared with healthy controls (P = 0.06). No significant differences between groups were detected in the posterior insula or occipital cortex (P > 0.05 for all comparisons). Within the right posterior insula, higher levels of GABA were positively correlated with pressure-pain thresholds in the FM patients (Spearman's rho = 0.63; P = 0.02).

Conclusion: Diminished inhibitory neurotransmission resulting from lower concentrations of GABA within the right anterior insula may play a role in the pathophysiology of FM and other central pain syndromes.

Figure 1

Voxel placement and resulting spectrum on magnetic resonance spectroscopy. A, Axial and sagittal T1-weighted brain images obtained from fibromyalgia patients show single-voxel placements (boxed areas) for the right anterior insula (ant Ins), right posterior insula (post Ins), anterior cingulate (ACC), and occipital cortex (Occ). B, A representative proton magnetic resonance spectroscopy spectrum from the posterior insula is shown, as determined using the multi-echo single-voxel point-resolved spectroscopy technique edited for γ-aminobutyric acid (GABA). The peak for the combined measure of glutamine and glutamate (Glx) is resolved at 3.8 parts per million, and the peak for GABA is resolved at 3.0 ppm, with an inverted N-acetylaspartate (NAA) peak at 2.0 ppm.

Figure 2

Levels of γ-aminobutyric acid (GABA) within the right anterior insula (A), anterior cingulate (B), right posterior insula (C), and occipital cortex (D) of individual patients with fibromyalgia (FM) compared with healthy controls (HC). FM patients have reduced concentrations of GABA in the right anterior insula, with a trend toward elevated concentrations of GABA in the anterior cingulate, as compared to healthy controls. There are no between-group differences in the right posterior insula or occipital cortex. Circles represent individual subjects; horizontal bars indicate the mean. AIU = arbitrary institutional units.

Figure 3

Levels of γ-aminobutyric acid (GABA) within the right posterior insula are positively correlated with pressure–pain thresholds in patients with fibromyalgia. Results are shown as a scatterplot of GABA concentrations in relation to slightly intense pressure–pain thresholds in individual patients (solid circles); the regression line is also shown. Correlations were assessed using Spearman's rho. AIU = arbitrary institutional units.