Upregulation of cortical GABAA receptor concentration in fibromyalgia

An imbalance between excitatory and inhibitory neurotransmission has been linked to fibromyalgia (FM). Magnetic resonance spectroscopy has shown increased levels of glutamate in the insula and posterior cingulate cortex in FM as well as reduced insular levels of gamma-aminobutyric acid (GABA). Both of these changes have been associated with increased pain sensitivity. However, it is not clear whether excitatory and/or inhibitory neurotransmission is altered across the brain. Therefore, the aim of this study was to quantify GABAA receptor concentration on the whole brain level in FM to investigate a potential dysregulation of the GABAergic system. Fifty-one postmenopausal women (26 FM, 25 matched controls) underwent assessments of pain sensitivity, attention and memory, psychological status and function, as well as positron emission tomography imaging using a tracer for GABAA receptors, [F]flumazenil. Patients showed increased pain sensitivity, impaired immediate memory, and increased cortical GABAA receptor concentration in the attention and default-mode networks. No decrease of GABAA receptor concentration was observed. Across the 2 groups, GABAA receptor concentration correlated positively with functional scores and current pain in areas overlapping with regions of increased GABAA receptor concentration. This study shows increased GABAA receptor concentration in FM, associated with pain symptoms and impaired function. The changes were widespread and not restricted to pain-processing regions. These findings suggest that the GABAergic system is altered, possibly indicating an imbalance between excitatory and inhibitory neurotransmission. Future studies should try to understand the nature of the dysregulation of the GABAergic system in FM and in other pain syndromes.