Alterations in metabolic flux in migraine and the translational relevance - The Journal of Headache and Pain
Source : https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-022-01494-w
Background Migraine is a highly prevalent disorder with significant economical and personal burden. Despite the development of effective therapeutics, the causes which precipitate migraine attacks remain elusive. Clinical studies have highlighted altered metabolic flux and mitochondrial function in patients. In vivo animal experiments can allude to the metabolic mechanisms which may underlie migraine susceptibility.
Conclusion: Migraine susceptibility may be underpinned by impaired metabolism resulting in depleted energy stores and altered neuronal function. This review discusses both clinical and in vivo studies which provide evidence of altered metabolic flux which contribute toward pathophysiology. It also reviews the translational relevance of animal studies in identifying targets of biomarker or therapeutic development.
• Source: The Journal of Headache and Pain
• Conclusion: “Migraine susceptibility may be underpinned by impaired metabolism resulting in depleted energy stores and altered neuronal function. This review discusses both clinical and in vivo studies which provide evidence of altered metabolic flux which contribute toward pathophysiology. It also reviews the translational relevance of animal studies in identifying targets of biomarker or therapeutic development.”
• The pathophysiology of migraine could involve mitochondrial and metabolic deficits. Migraine patients exhibit mitochondrial disorders and structural and biochemical impairments in the electron transfer chain.
• CGRP is a major nociceptive peptide involved in migraine and exhibits a reciprocal relationship with multiple metabolic pathways such as glucose and lipid use.
• The effects of CGRP antagonism on insulin function remains to be elucidated. In animal models, CGRP antagonism improves oral glucose tolerance.
• Headache could be an adverse effect of diabetes. Pramlintide, an amylin receptor agonist, is approved for diabetes treatment in the U.S. and off-target effects could activate the trigeminovascular system.
• “It is still uncertain as to whether metabolic deficits result in excessive CGRP-mediated nociception or vice versa. Attributing metabolic perturbations exclusively to migraine may be difficult, since common migraine comorbidities also feature some metabolic alterations such as obesity and depression. However, both clinical and in vivo evidence suggests that an imbalance between energetic demand and supply may contribute towards migraine pathology. Therefore, perturbation of metabolic pathways which exacerbate this imbalance may be the basis for the metabolic component of migraine,” the authors wrote.