” The authors propose that this central neuronal hyperexcitability involves overactivity of the excitatory amino acids, glutamate, and possibly asparate. Stimuli that activate the migraine attack evoke neuronal depolarization, slow deplorization shifts, and spreading suppression of spontaneous neuronal activity possible by glutamate and K+dependent mechanisms. A low brain Mg2+ and consequent reduced gating of glutamatergic receptors may provide the link between the physiologic threshold for a migraine attack and the mechanisms of the attack itself by promoting glutamate hyperactivity, neuronal hyperexcitability, and susceptibility to glutamate-dependant spreading depression.” The Concept of Migraine as a State of Central Neuronal Hyperexcitability https://www.neurologic.theclinics.com/article/S0733-8619(18)30319-0/abstract
“The trigeminal system is considered to play a key role in migraine pathophysiology, trafficking pain signals from the head and face to the trigeminal nucleus caudalis. The role of glutamate in the pathophysiology of migraine is implicated by data from animal and human studies. Animal studies include experiments of cortical spreading depression, studies of c-fos protein expression in trigeminal nucleus caudalis, studies of plasma protein extravasation and electrophysiological studies. Human studies investigating the role of Glu in migraine pathogenesis measured the levels of Glu in plasma, platelets and cerebrospinal fluid, studied its effect on migraine symptoms and examined the effect of Glu in modulating sensitization. Findings from both the animal and the human studies suggest a link between glutamate and migraine and further suggest that glutamate plays a key role in migraine mechanisms. In the future, efforts should be made to further investigate the role of glutamate in migraine pathogenesis and, subsequently, in migraine treatment.” The Role of Glutamate and its Receptors in Migraine http://www.ingentaconnect.com/content/ben/cnsnddt/2007/00000006/00000004/art00006
“The red line in the Graph 2 above shows typical glutamate levels during the menstrual cycle. You can see that just before and during menstruation, when migraines are most likely to occur, estrogen and progesterone levels are low but glutamate levels are high. Glutamate is your primary neurotransmitter (it carries your thoughts) and has been a primary suspect in the hunt for the cause of migraine since the 1970’s. You may know glutamate best as the migraine trigger monosodium glutamate, also known as “MSG.”“Men consistently have more glutamate (with 211) than women (93-169). Excessive glutamate is a migraine trigger. However, men consistently have more glutamate scavengers GOT and GPT. It is well established that excessive concentrations of glutamate between neurons (termed excitotoxicity) (study link) are associated with stroke, bacterial meningitis, seizures, Alzheimer’s disease, and migraine with aura. GOT and GPT scavengers have proven to reduce glutamate levels as well as reduce the levels of glutamate between neurons (study link). Men may have more glutamate, but they also have more of these glutamate scavengers that prevent a toxic buildup of glutamate between the cells.” https://www.migrainekey.com/blog/estrogen-and-progesterone/
“Glutamate receptor-subtype antagonists are effective in preclinical models of migraine, and in the clinic. These preclinical and clinical observations argue for a strong link between migraine and the glutamatergic system, a link that is important to further characterize in an effort to better understand migraine mechanisms and deliver effective therapies.” The Link Between Glutamate and Migraine https://www.cambridge.org/core/journals/cns-spectrums/article/link-between-glutamate-and-migraine/20887A73E54EC85DAE5FB84BA06482CF
“Both preclinical and clinical data link glutamate to the migraine pathophisiology. Altered plasma, platelets and cerebrospinal (CSF) glutamate levels have been reported in migraine patients. Chronic migraine is comorbid with several conditions. It has been recently shown chronic migraine comorbidity with fibromyalgia. The objective of this study was to study cerebrospinal fluid glutamate levels in chronic migraine patients with and without fibromyalgia. We studied 20 chronic migraine patients, with and without fibromyalgia, compared to age‐sex matched controls. CSF glutamate levels were measured by HPLC. CSF glutamate demonstrated significantly higher levels in patients with fibromyalgia compared to those without fibromyalgia. Patients overall had higher CSF glutamate levels than controls. Mean pain score correlated with glutamate levels in chornic migraine patients. Tender points, the hallmark of fibromyalgia, can be considered as pressure allodynia, and is probably mediated by central sensitization, with increase in CSF glutamate levels. We postulate chronic migraine patients with fibromyalgia, in addition to have more disabling headaches, suffer from a more severe central sensitization process. This subtype of patients may respond to medications modulating glutamate receptors. Headache intensity correlate with glutamate levels in chronic migraine patients.” Cerebrospinal fluid glutamate levels in chronic migraine https://onlinelibrary.wiley.com/doi/full/10.1111/j.1468-2982.2004.00750.x
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