Scientists Identify Brain Mechanisms Behind Migraines

Migraine, a debilitating neurological disorder, affects over 1 billion people worldwide. Despite its prevalence, the underlying causes of migraine have long been shrouded in mystery. However, groundbreaking new research from the University of Rochester is providing fresh insights into the complex brain mechanisms that trigger these intense headaches.

The study reveals how a wave of disruption spreads across the brain during a migraine with aura, releasing inflammatory proteins into the cerebrospinal fluid that activate pain-signaling nerves.1 These findings open up exciting new avenues for developing more targeted and effective therapies.

Research Links Brain Fluid Flow to Migraine Headaches

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Researchers at the University of Rochester have discovered that during a migraine with aura, a wave of disruption spreads across the brain, releasing inflammatory proteins into the cerebrospinal fluid. These proteins are then carried to pain-signaling nerves, activating them and causing the excruciating headache.

The study also identified specific proteins that could serve as targets for new migraine medications.

“These findings provide us with a host of new targets to suppress sensory nerve activation to prevent and treat migraines and strengthen existing therapies,” said lead author Maiken Nedergaard, MD.(ref)

Cerebrospinal Fluid: The Missing Link?

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The findings provide the first clear evidence linking cortical spreading depression (CSD) – the brain wave associated with migraine aura – to headache pain.

During CSD, neurons temporarily depolarize, impairing blood flow and oxygen levels. This wave was found to release proteins into the cerebrospinal fluid that bathes the brain.

Surprisingly, the researchers discovered a previously unknown gap in the blood-brain barrier that allows these CSF proteins to directly enter the trigeminal ganglion, a cluster of sensory nerves that relay pain signals from the head and face. There, a dozen different proteins were found to bind to and activate the nerves, likely triggering migraine pain.

Explaining the Mysteries of Migraine

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The study helps explain several puzzling aspects of migraines:

  • Why migraine pain is often one-sided: Proteins released on one side of the brain primarily activated nerves on the same side.
  • How migraine aura leads to headache: The CSD wave triggers protein release into CSF, activating pain nerves.
  • Potential of new targeted treatments: Blocking the identified pain-triggering proteins could stop migraines at the source.

One of the proteins, CGRP, is already the target of new migraine drugs, validating the study’s approach. But the findings reveal a whole new array of potential therapeutic targets.

Current & Emerging Migraine Treatments

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While there is no cure for migraines, a variety of treatments are available to help manage symptoms and reduce the frequency of attacks. These include:

  • Acute medications: Triptans, ergotamines, and over-the-counter pain relievers can help stop a migraine attack once it has started. Newer medications like gepants and ditans target CGRP receptors without causing blood vessel constriction.
  • Preventive medications: Beta-blockers, antidepressants, anticonvulsants, and CGRP monoclonal antibodies can help reduce the frequency and severity of migraines when taken regularly. Botox injections are also FDA-approved for chronic migraine prevention.
  • Neuromodulation devices: Non-invasive devices that use electrical or magnetic stimulation to modulate nerve activity, such as the Cefaly, gammaCore, and sTMS mini devices, have shown promise in preventing and treating migraines.(ref)
  • Lifestyle changes: Identifying and avoiding migraine triggers, maintaining a regular sleep schedule, managing stress, staying hydrated, and exercising regularly can help reduce the frequency of attacks.

Researchers continue to explore new treatment options, such as small molecule CGRP receptor antagonists, pituitary adenylate cyclase-activating polypeptide (PACAP) antibodies, and more targeted neuromodulation techniques. Personalized treatment approaches based on an individual’s genetics, triggers, and comorbidities may also become more common in the future.

By understanding the fluid dynamics of the brain and how CSD leads to pain signaling, researchers are closer than ever to unraveling the complex neurobiology of migraines. While more research is needed, this study marks a significant leap forward, cracking open the black box of migraine headaches and pointing the way to more effective treatments for millions of migraine sufferers worldwide.

Source:

  1. Science
Martha A. Lavallie
Martha A. Lavallie
Author & Editor | + posts

Martha is a journalist with close to a decade of experience in uncovering and reporting on the most compelling stories of our time. Passionate about staying ahead of the curve, she specializes in shedding light on trending topics and captivating global narratives. Her insightful articles have garnered acclaim, making her a trusted voice in today's dynamic media landscape.