Metabolomic insights into migraine: mechanisms and biomarkers from in vivo and clinical studies.

Migraine is a complex neurological disorder characterized by recurrent attacks of moderate to severe headaches with nausea, photophobia, and phonophobia. Although advances in neuroimaging have improved diagnostic capabilities and options of treatment, the diagnosis and management of migraine still depend primarily on clinical symptoms. Many studies have reported that metabolomics, the comprehensive analysis of small-molecule metabolites, offers a promising approach for elucidating the neuro-pathophysiology and identifying novel biomarkers or therapeutic targets of migraine. Several in vivo studies have demonstrated that migraine is associated with metabolic alterations, including impaired energy metabolism, altered glucose utilization, decreased levels of high-energy phosphate intermediates, and increased lactate concentrations. In addition, elevated levels of excitatory neurotransmitters, decreased levels of inhibitory neurotransmitters, increased oxidative stress, and reduced antioxidant levels have been observed in both the brain and blood of animal models with migraine. Clinical studies have also confirmed alterations in metabolomic profiles, with additional evidence of disrupted lipid and amino acid metabolism during both the ictal and interictal phases of migraine. Several interventional studies, including those involving acupuncture, tetramethylpyrazine, Ligusticum chuanxiong, ibuprofen, and triptans, have demonstrated that these interventions can partially reverse these metabolic derangements. Therefore, the present review aims to summarize and discuss findings from both in vivo and clinical studies regarding metabolomics and migraine. Any contradictory findings are also included in this review.