Targeting Glutamate Neurotoxicity through Dietary Manipulation: Potential Treatment for Migraine

Glutamate, the main excitatory neurotransmitter in the central nervous system, is implicated in both the initiation of migraine as well as central sensitization, which increases the frequency of migraine attacks. Excessive levels of glutamate can lead to excitotoxicity in the nervous system which can disrupt normal neurotransmission and contribute to neuronal injury or death. Glutamate-mediated excitotoxicity also leads to neuroinflammation, oxidative stress, blood-brain barrier permeability, and cerebral vasodilation, all of which are associated with migraine pathophysiology. Experimental evidence has shown the protective effects of several nutrients against excitotoxicity. The current review focuses on the mechanisms behind glutamate's involvement in migraines as well as a discussion on how specific nutrients are able to work towards restoring glutamate homeostasis. Understanding glutamate's role in migraine is of vital importance for understanding why migraine is commonly comorbid with widespread pain conditions and for informing future research directions.