Altered Neurotransmitter Ratio in the Prefrontal Cortex is Associated with Pain in Fibromyalgia Syndrome

Abstract

ABSTRACTThe central mechanisms underlying fibromyalgia syndrome (FMS) remain undetermined. The dorsolateral prefrontal cortex (DLPFC) is particularly relevant to FMS because it is implicated in cognitive, affective, and top-down pain regulation. Imbalances in excitatory (Glutamate) and inhibitory (Gamma aminobutyric acid; GABA) neurochemicals may play a critical role in the pathophysiology of the condition and more generally in homeostatic function within cortical circuits. Although the balance of excitation and inhibition are intrinsically linked no investigations to date have investigated the E/I ratio in FMS. Thus, the primary objective of this study was to determine whether the E/I ratio in the DLPFC is altered in participants with FMS compared to healthy controls using magnetic resonance spectroscopy. Additionally, we examined the relationship between E/I ratio and pain metrics. We hypothesized that the E/I ratio within the DLPFC would be altered in participants with FMS compared to controls and, secondly, that E/I ratio would be associated with both clinical pain and thermal pain sensitivity. The Brief Pain Inventory (BPI) self-assessment was used to evaluate pain severity and impact on physical functioning and acute pain sensitivity was determined via quantitative sensory testing to define thermal (heat) pain threshold and tolerance. Our results revealed an elevation in the E/I ratio in FMS compared to controls. A positive relationship between E/I ratio and thermal pain sensitivity measures was identified in the FMS cohort. Collapsing across groups, there was a positive relationship between E/I ratio and BPI score. These findings suggest that dysfunction in the balance between excitation and inhibition within cognitive brain circuitry may play a role in pain processing in FMS.