Indirect Regulation of Na+, K+-ATPase by Arachidonic Acid-Derived Eicosanoids: Participation of Eicosanoids in the Sodium Theory for Migraine

Migraines are a debilitating headache disorder affecting over a billion people worldwide. Migraine pathology is neurovascular. The neuroactivational aspect is strongly influenced by sodium ion concentration in the cerebrospinal fluid. Cerebrospinal fluid sodium levels' regulation primarily depends on the sodium pump Na+, K+-ATPase in the choroid plexus. The sodium theory for migraine suggests that the dysregulation of Na+, K+-ATPase in migraineurs results in elevated cerebrospinal fluid sodium, which is known to increase central sensitization, thereby predisposing these individuals to headaches. The involvement of eicosanoids in migraine pathology is well documented. Indirect regulation of Na+, K+-ATPase by eicosanoids is documented for many tissues including the brain. The focus of this review is to identify which eicosanoids are involved in both migraine and Na+, K+-ATPase regulation in a manner consistent with the sodium theory for migraine. We believe that the identification of such eicosanoids may lead to the development of new pharmaceuticals to address migraines.