Abstract
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 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 neurotransmitters in migraine pathology is well documented. Indirect regulation of Na+, K+-ATPase by neurotransmitters is well documented for many tissues including the brain. The focus of this review is to identify which neurotransmitters 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 neurotransmitters may lead to the development of new pharmaceuticals to address migraines.