A Paradoxical Vasodilatory Nutraceutical Intervention for Prevention and Attenuation of Migraine—A Hypothetical Review

Abstract

Studies suggest that migraine pain has a vascular component. The prevailing dogma is that peripheral vasoconstriction activates baroreceptors in central, large arteries. Dilatation of central vessels stimulates nociceptors and induces cortical spreading depression. Studies investigating nitric oxide (NO) donors support the indicated hypothesis that pain is amplified when acutely administered. In this review, we provide an alternate hypothesis which, if substantiated, may provide therapeutic opportunities for attenuating migraine frequency and severity. We suggest that in migraines, heightened sympathetic tone results in progressive central microvascular constriction. Suboptimal parenchymal blood flow, we suggest, activates nociceptors and triggers headache pain onset. Administration of NO donors could paradoxically promote constriction of the microvasculature as a consequence of larger upstream central artery vasodilatation. Inhibitors of NO production are reported to alleviate migraine pain. We describe how constriction of larger upstream arteries, induced by NO synthesis inhibitors, may result in a compensatory dilatory response of the microvasculature. The restoration of central capillary blood flow may be the primary mechanism for pain relief. Attenuating the propensity for central capillary constriction and promoting a more dilatory phenotype may reduce frequency and severity of migraines. Here, we propose consideration of two dietary nutraceuticals for reducing migraine risk: L-arginine and aged garlic extracts.

The Relationship Between Nitrate-Induced Headache and -Blood Viscosity: An Observational Prospective Study

“…Rather, it has been proposed that with dilation of the great arteries, there is vasoconstriction downstream of the cerebral microcirculation, raising the notion of an alternative causation. 17,22 One of the major determinants of cerebral blood flow is blood viscosity, and studies have shown that cerebral blood flow regulation has a dominant role in primary headaches such as migraine. [23][24][25][26] Whole blood is a non-newtonian fluid, which means that the viscosity of the blood depends on the shear rate.…”

“…[12][13][14] In our study, we found more NIH development in those with high WBV. This effect may be due to reflex vasoconstriction in the microvascular bed as a result of vasodilation of the large cerebral arteries, 17,22 further accentuating the effect of blood viscosity, which is of critical importance for blood flow. Because nitrates cause reflex vasoconstriction at the microvascular level, impair tissue perfusion, and stimulate nociceptors, we can say that blood viscosity, which has a stable hemorheological status under normal conditions, differentiates its hemorheological properties after nitrate use and shows a significant interaction in blood flow mechanics.…”

Dysregulation of Amino Acid, Lipid, and Acylpyruvate Metabolism in Idiopathic Intracranial Hypertension: A Non-targeted Case Control and Longitudinal Metabolomic Study

“…In CSF, pathway enrichment analysis identified arginine/proline metabolism and glutamate/glutamine metabolism as associated to one clinical symptom (MD worst eye). Arginine metabolism has previously been linked to the development and treatment of migraines through its role in the synthesis of nitric oxide. − Nitric oxide is synthesized from arginine by the endothelial nitric oxide synthase and synthesizes citrulline as a byproduct. , Nitric oxide is important in smooth muscle relaxation, vasodilation, and increased blood flow and is a potent headache provocation agent . It is possible that the perturbed arginine metabolism with downstream effects on nitric oxide may be linked to the severe headache phenotype in IIH .…”

Garlic and allopurinol alleviate the apoptotic pathway in rats’ brain following exposure to fipronil insecticide

“…Now, there is an enlarged use of natural products as an antioxidant instead of synthetic chemicals [46]. In this respective, the alleviation efficacy of garlic may be due to its antioxidant properties as the garlic can scavenge reactive oxygen species [47], specifically superoxide radicals [48], and neutralize hydrogen peroxide, by causing the increase in the activity of SOD, CAT, and GPx, leading to prevention of hydrogen peroxide-induced cell damage [49]. Garlic also can obstruct lipid peroxidation by scavenging the hydroxyl and peroxyl radicals [50].…”