Ray mentioned the topic of migraines many times in his articles. He implicated estrogen, serotonin, NO and mitochondrial dysfunction as the main drivers behind it. The study below corroborates that view and demonstrated that all that is required for a migraine to occur is a drop in oxidative metabolism, which means a shift towards a reduced state and anaerobic metabolism. It goes without saying that in such a state, lactate production increases, which leads to increased synthesis of serotonin (5-HT), which then increases synthesis and release of NO. The vasodilatory effects of NO, as well as pain-sensitizing effects of 5-HT and lactate, are the direct causes of migraine, but once again metabolism is exposed as the top-level regulator of the entire process. In other words, migraines are nothing more than a symptom of low metabolic rate in the central/peripheral nervous system. As such, pro-metabolic substances may be therapeutic and ones with a direct anti-NO effects such as methylene blue (MB) may be ideally suited for this issue. However, one has to be careful with MB since in higher doses it is a potent inhibitor of monoamine oxidase type A (MAO-A), which can result in increased 5-HT and thus negate the pro-metabolic benefits of MB for migraine patients. Most of the clinical studies with mental and neurological conditions found that the benefits of MB peak at about 15mg daily, and in my own experience even lower doses in the 1mg-5mg range work just as well, while keeping MAO-A risks even lower.
https://pubmed.ncbi.nlm.nih.gov/41507943/
Mitochondrial Dysfunction Drives Peripheral Hypersensitivity in Migraine
“…In recent years, the field of migraine research has witnessed a surge of interest, particularly regarding the underlying mechanisms that contribute to this debilitating neurological condition. A groundbreaking study has shed light on the multifaceted relationship between mitochondrial dysfunction in the spinal cord and peripheral hypersensitivity in a nitroglycerin-induced migraine model. This research, conducted by Awad-Igbaria and colleagues, illuminates the crucial role that the spinal cord and its mitochondria play in modulating pain pathways associated with migraines.”
“…”The nitroglycerin-induced migraine model has been extensively used in experimental studies to emulate the clinical characteristics of migraine attacks in humans. By administering nitroglycerin (a precursor to nitric oxide), researchers can trigger a cascade of biochemical reactions that mimic the neurovascular changes seen during a typical migraine episode. In this study, the authors utilized this model to explore how mitochondrial integrity influences nociceptive signaling pathways during migraine attacks.”
“…One of the most striking revelations from this study is the correlation between mitochondrial function and the exacerbation of pain signals in the spinal cord. The researchers observed that impaired mitochondrial dynamics led to an increase in pro-inflammatory cytokines and reactive oxygen species, both of which are exacerbated in migraine sufferers. This inflammatory response is critical, as it heightens sensitivity in the nervous system, resulting in allodynia—a condition where non-painful stimuli are perceived as painful. Furthermore, the study delves into the role of metabolic alterations that occur alongside mitochondrial dysfunction. As energy production falters, cells in the spinal cord shift to rely on anaerobic pathways, leading to metabolic byproducts that may further sensitize pain pathways. This metabolic imbalance is believed to create a feedback loop, aggravating the hypersensitivity experienced by individuals with migraines.”
Via: https://haidut.me/?p=2938
