Article

Reduced insular ?????aminobutyric acid in fibromyalgia

University of Michigan and Ann Arbor VA Healthcare System, Ann Arbor, Michigan, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 02/2012; 64(2):579-83. DOI: 10.1002/art.33339
Source: PubMed

ABSTRACT

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.
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.
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).
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.

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    • "FM patients experience pain at lower dermal pressure thresholds compared to healthy controls (HC), and pain perception is accompanied by increased signals in typical pain processing areas like insula, ACC, somatosensory and supplementary motor cortices (SMA), but also basal ganglia and inferior parietal and cerebellar foci [1] [11]. Magnetic resonance spectroscopy showed increased concentrations of glutamate and decreased γ-aminobutyric acid in insular cortices in FM [13] [14]. other-perspective (i.e. "
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    ABSTRACT: Dysfunction of central nervous pain processing is assumed to play a key role in primary fibromyalgia (FM) syndrome. This pilot study examined differences of pain processing associated with adopting different interpersonal perspectives. Eleven FM patients and 11 healthy controls (HC) were scanned with functional magnetic resonance imaging. Participants were trained to take either a self-perspective or another person's perspective when viewing the visual stimuli. Stimuli showed body parts in painful situations of varying intensity (low, medium, and high) and visually similar but neutral situations. Patients with FM showed a higher increase in blood oxygen level dependent (BOLD) response, particularly in the supplementary motor area (SMA). All pain-related regions of interest (anterior insula, somatosensory cortices, anterior cingulate cortex, and SMA) showed stronger modulation of BOLD responses in FM patients in the self-perspective. In contrast to pain processing regions, perspective-related regions (e.g. temporoparietal junction) did not differ between FM and HC. The stronger response of all four pain processing cerebral regions during self-perspective is discussed in the light of disturbed bottom-up processing. Furthermore, the results confirm earlier reports of augmented pain processing in FM, and provide evidence for sensitization of central nervous pain processing. Copyright © 2015 Elsevier Inc. All rights reserved.
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    • "Our group has reported increased levels of Glx in FM subjects in the posterior insula which is responsible for the graded sensory processing of pain [5] [6]. Our group has also reported decreased levels of GABA in FM subjects in the anterior insula which is important in the emotional processing and affective aspects of pain [6] [7]. Lower NAA levels within the hippocampus has also been reported in the setting of FM [8]. "

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    • "Our group has reported increased levels of Glx in FM subjects in the posterior insula which is responsible for the graded sensory processing of pain [5] [6]. Our group has also reported decreased levels of GABA in FM subjects in the anterior insula which is important in the emotional processing and affective aspects of pain [6] [7]. Lower NAA levels within the hippocampus has also been reported in the setting of FM [8]. "
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    ABSTRACT: 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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