Migraine: from pathophysiology to treatment

Abstract

Migraine is an extremely disabling, common neurological disorder characterized by a complex neurobiology, involving a series of central and peripheral nervous system areas and networks. A growing increase in the understanding of migraine pathophysiology in recent years has facilitated translation of that knowledge into novel treatments, which are currently becoming available to patients in many parts of the world and are substantially changing the clinical approach to the disease. In the first part of this review, we will provide an up to date overview of migraine pathophysiology by analyzing the anatomy and function of the main regions involved in the disease, focusing on how these give rise to the plethora of symptoms characterizing the attacks and overall disease. The second part of the paper will discuss the novel therapeutic agents that have emerged for the treatment of migraine, including molecules targeting calcitonin gene-related peptide (gepants and monoclonal antibodies), serotonin 5-HT1F receptor agonists (ditans) and non-invasive neuromodulation, as well as providing a brief overview of new evidence for classic migraine treatments.

Update on gepants for the treatment of chronic migraine

“…CGRPs are also strongly associated with CM, with previous studies showing higher serum levels of CGRPs among patients with CM compared with patients with EM or no headache. 12,19 These findings have established the vital role of CGRPs in the pathophysiology of migraine. To achieve effective acute or preventative treatment, CGRP antagonists acting on CGRP receptors or ligands have been developed.…”

“…13 In addition to this effect of the trigeminovascular system on brainstem regions, its activation further affects the hypothalamus, thalamus, and cortex, resulting in the unique features of migraine. 12 CM has different mechanisms and presentations comparing with those of EM. 14 Multiple studies have indicated a strong correlation between structural and functional changes in specific brain regions associated with pain sensitization and top-down pain modulation.…”

“…According to current understanding and scientific research, trigeminovascular system activation with vasodilatation and neuroinflammation is regarded as the primary mechanism for migraine. 12 This activation also affects brainstem regions, with second-order neurons projecting into areas such as the dorsolateral pons and periaqueductal gray, which play different roles in migraine. 13 In addition to this effect of the trigeminovascular system on brainstem regions, its activation further affects the hypothalamus, thalamus, and cortex, resulting in the unique features of migraine.…”

Migraine and Its Treatment from the Medicinal Chemistry Perspective

“…Today, lasmiditan is the only ditan available. 103 The 5-HT1F receptor agonist lasmiditan is a centrally acting, selective, and high-affinity compound. It acts on the trigeminovascular system, inhibiting neurotransmitter release without causing vasoconstriction.…”

“…Today, lasmiditan is the only ditan available . The 5-HT1F receptor agonist lasmiditan is a centrally acting, selective, and high-affinity compound.…”