Excitation-Inhibition Imbalance in Migraine: From Neurotransmitters to Brain Oscillations

Abstract

Migraine is among the most common and debilitating neurological disorders typically affecting people of working age. It is characterised by a unilateral, pulsating headache often associated with severe pain. Despite the intensive research, there is still little understanding of the pathophysiology of migraine. At the electrophysiological level, altered oscillatory parameters have been reported within the alpha and gamma bands. At the molecular level, altered glutamate and GABA concentrations have been reported. However, there has been little cross-talk between these lines of research. Thus, the relationship between oscillatory activity and neurotransmitter concentrations remains to be empirically traced. Importantly, how these indices link back to altered sensory processing has to be clearly established as yet. Accordingly, pharmacologic treatments have been mostly symptom-based, and yet sometimes proving ineffective in resolving pain or related issues. This review provides an integrative theoretical framework of excitation–inhibition imbalance for the understanding of current evidence and to address outstanding questions concerning the pathophysiology of migraine. We propose the use of computational modelling for the rigorous formulation of testable hypotheses on mechanisms of homeostatic imbalance and for the development of mechanism-based pharmacological treatments and neurostimulation interventions.

Assessing the balance between excitation and inhibition in chronic pain through the aperiodic component of EEG

“…It is plausible that E/I imbalances are more prominent in specific subtypes of chronic pain. For example, clinical observations suggest that changes in excitability are particularly relevant in chronic widespread pain (CWP) (Sluka and Clauw, 2016) and migraine (O'Hare et al, 2023), but possibly less in other chronic pain conditions. Our findings are compatible with this possibility, as they showed robust negative evidence in people with CBP, but partially inconclusive evidence in our small sample of people with CWP.…”