Indirect Regulation of Na+, K+-ATPase by Endocrine Hormones: Participation of Endocrine Hormones in the Sodium Theory for Migraine

The European Migraine and Headache Alliance (https://www.emhalliance.org) estimates that migraine is one of the top ten leading causes of disability and affects 12-15% of the population. 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 (NKA) in the choroid plexus. The sodium theory for migraine suggests that the dysregulation of NKA in migraineurs results in elevated CSF sodium, which is known to increase central sensitization, thereby predisposing these individuals to headaches. The involvement of endocrine hormones in migraine pathology is well documented. Indirect regulation of NKA by endocrine hormones is well documented for many tissues including the brain. The focus of this review is to identify which endocrine hormones are involved in both migraine and NKA regulation in a manner consistent with the sodium theory for migraine. We believe that the identification of such endocrine hormones may lead to the development of new pharmaceuticals to address migraine.