Migraines have long been shrouded in mystery, but recent breakthroughs have shed light on the complex mechanisms behind these debilitating headaches. For decades, researchers thought that migraines were primarily a problem of blood vessels in the brain. But in the past two decades, a new understanding has emerged: dysfunctional nerve signaling is also at play.
The Trigeminal Nerve and CGRP: The Migraine Duo
Key players in migraine are the trigeminal nerves and a signaling molecule called calcitonin gene-related peptide (CGRP). These two entities have become the focus of innovative treatments. CGRP antibodies, for instance, can prevent migraines from occurring in the first place. And acute treatment options like ditans and CGRP gepants have been designed to target this molecule.
The Trigeminal Nerve: More Than Just Facial Sensation
The trigeminal nerve is responsible for sensation in the face, head, and jaw, as well as jaw movement like biting and chewing. Its three branches reach the eye, forehead, and jaw, respectively. CGRP, a neuropeptide, plays a crucial role in migraine theory. When a migraine attack begins, the trigeminal nerve releases CGRP, which causes blood vessels to swell, contributes to inflammation, and activates pain pathways.
The Lock-and-Key Analogy: How New Medications Disrupt Migraine Pain
Think of CGRP as the key and its receptor as the lock. When the key opens the lock, the pain process begins or worsens. New medications that block the lock (CGRP antibodies) or change the shape of the key (ditans and CGRP gepants) interfere with CGRP’s function, treating migraine.
A Breakthrough in Migraine Prevention: CGRP Antibodies
The approval of the first CGRP antibodies in 2018 marked a significant milestone. These medications are specifically designed to prevent migraines from occurring. Four such drugs are now available, and high-quality trials have shown they reduce the number or severity of migraine days.
Acute Migraine Treatment: The Rise of Ditans and CGRP Gepants
In late 2019 and early 2020, three new drugs were approved for acute treatment of migraines. These medications stop migraine attacks when they start. Ubrelvy (ubrogepant) and Nurtec (rimegepant) are part of the CGRP gepants family, binding to the CGRP receptor to prevent pain processes. Reyvow (lasmiditan) is the only ditan drug, which reduces CGRP release by activating serotonin receptors.
Older Medications: A Surprising Connection to CGRP
Some older and non-specific medications may actually affect CGRP levels. For example, sumatriptan blocks the release of CGRP from trigeminal nerves. It’s possible that their effectiveness isn’t solely due to their effect on blood vessels.
Botox: A Game-Changer in Migraine Prevention
Originally used for wrinkles and other cosmetic concerns, Botox was approved in 2010 for migraine prevention in people with chronic migraines. Further research has shown it reduces CGRP levels between attacks.
The science behind migraines is complex, but the discovery of dysfunctional nerve signaling and CGRP’s role has opened doors to innovative treatments. With these new options, people suffering from migraines may finally find relief.
