How Does CGRP Cause Migraine?

CGRP (calcitonin gene-related peptide), a protein released around the brain that can dilate blood vessels and cause severe inflammation, is believed to cause the pain of a migraine headache.

A migraine is a neurological disorder that causes a severe headache along with sensitivity to light, sound, or smells.

CGRP (calcitonin gene-related peptide) is a protein that, when released around the brain, dilates blood vessels and causes severe inflammation in the coverings of the brain (the meninges). For most migraine patients, this results in the pain of a migraine attack.

• It is not entirely understood how CGRP causes the pain of migraines. One theory is that CGRP sensitizes peripheral nerves, which in turn send signals to the central nervous system (CNS) that trigger the pain and sensitivity to sensory stimuli associated with migraine. This may occur because when CGRP binds to its receptor, it sensitizes the nerves by increasing their rate of firing. CGRP might also activate pain receptors by dilating blood vessels, which could push on pain receptors on adjacent nerves. 
• In some people, certain foods may induce a migraine attack and it is possible CGRP also acts in the gastrointestinal tract to trigger migraine attacks.

Symptoms of migraine are typically characterized by five phases: 

• Prodrome: warnings before a migraine
  • Subtle changes in sensations such as an unusual taste or smell
  • Fatigue
  • Muscle tension 
  • Mood changes
• Aura: visual disturbances that precede the headache phase
  • Geometric patterns or flashing, colorful lights
  • Blind spots (scotomas)
  • Loss of vision on one side (hemianopsia)
• Headache
  • May last 4-72 hours
  • Usually occurs on one side of the head, but may occur on both sides
  • Throbbing pain 
  • Nausea
  • Vomiting
  • Sensitivity to light (photophobia) 
  • Sensitivity to sound (phonophobia)
• Headache termination
  • Pain usually goes away with sleep, even if the migraine is not treated
• Postdrome: other signs can linger after the pain goes away
  • Fatigue
  • Problems concentrating
  • Inability to eat

Treatment for migraine headaches includes: 

• Calcitonin-gene related peptide (CGRP) antagonists
  • Monoclonal antibodies
    • Administered by injection once every month or once every three months, depending on the medication 
      • Eptinezumab (Vyepti)
      • Erenumab (Aimovig)
      • Fremanezumab (Ajovy) 
      • Galcanezumab (Emgality)
  • Oral gepants (an older class of CGRP antagonist) 
    • Rimegepant (Nurtec)
    • Ubrogepant (Ubrelvy)
• Non-medical treatments
  • Ice 
  • Heat
  • Getting adequate hydration
  • Deep breathing
  • Darkened room/covering your eyes
  • Rest
  • Massage
  • Biofeedback
• Pain relievers
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Aspirin 
  • Acetaminophen (Tylenol)
  • Analgesics containing caffeine often work best
• Other medications
  • Triptans
  • Trigger point injections
  • OnabotulinumtoxinA (Botox)
• Anti-nausea medications (antiemetics)
  • Chlorpromazine, droperidol, prochlorperazine, and diphenhydramine
• Selective serotonin 1F receptor agonist
  • Lasmiditan (Reyvow)
• Ergotamine preparations
  • Dihydroergotamine (D.H.E. 45, Migranal)
  • Ergotamine (Ergomar)
• Neuromodulation
  • Transcutaneous supraorbital nerve stimulation 
  • Transcranial magnetic stimulation (TMS) 
  • Remote electrical neuromodulation 
  • Noninvasive vagus nerve stimulation (nVNS) 
• Peripheral nerve blocks
  • Occipital nerve blocks 
  • Sphenopalatine ganglion blocks