Glutamate as a Therapeutic Substrate in Migraine
Abstract
Recurrent and intense headache is a well appreciated cardinal feature of migraine, a common and incapacitating neurological disorder. Often, there are associated canonical sensory abnormalities, such as light and sound sensitivity, as well as associated nausea. Given this phenotype of disordered sensory processing and, in a third of patients, the phenomenon called aura accompanying migraine attacks, it has been suggested that the pathophysiology of migraine is likely to involve glutamate, the main excitatory neurotransmitter in the central nervous system (CNS). Glutamate plays a role in nociception, central sensitization, and cortical spreading depression (CSD), three processes that are deemed important in migraine biology. With an emphasis on the therapeutic potential of targeting various glutamate receptors in migraine, this review will discuss the currently available literature and emerging findings on the role of targeting glutamatergic pathways for the treatment of migraine. A thorough literature review was carried out on the functions of both metabotropic glutamate receptors (mGluRs), and the ionotropic glutamate receptors (NMDA, AMPA, and kainate) in migraine pathogenesis. The ever-present need for new treatments, the role of glutamate in the migraine aura phenomenon, and the consequences of monogenic migraine mutations on mediating prolonged, complex, or permanent aura are all discussed, culminating in a suggestion that glutamatergic targeting may hold particular…
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