New Insights on Metabolic and Genetic Basis of Migraine: Novel Impact on Management and Therapeutical Approach

Abstract

Migraine is a hereditary disease, usually one-sided, sometimes bilateral. It is characterized by moderate to severe pain, which worsens with physical activity and may be associated with nausea and vomiting, may be accompanied by photophobia and phonophobia. The disorder can occur at any time of the day and can last from 4 to 72 h, with and without aura. The pathogenic mechanism is unclear, but extensive preclinical and clinical studies are ongoing. According to electrophysiology and imaging studies, many brain areas are involved, such as cerebral cortex, thalamus, hypothalamus, and brainstem. The activation of the trigeminovascular system has a key role in the headache phase. There also appears to be a genetic basis behind the development of migraine. Numerous alterations have been identified, and in addition to the genetic cause, there is also a close association with the surrounding environment, as if on the one hand, the genetic alterations may be responsible for the onset of migraine, on the other, the environmental factors seem to be more strongly associated with exacerbations. This review is an analysis of neurophysiological mechanisms, neuropeptide activity, and genetic alterations that play a fundamental role in choosing the best therapeutic strategy. To date, the goal is to create a therapy that is as personalized as possible, and for this reason, steps forward have been made in the pharmacological field in order to identify new therapeutic strategies for both acute treatment and prophylaxis.

Keywords: cortical spreading depression; genetics; migraine; neurobiology.

Figure 1

Multiple cortical areas process input from TCC.