Science of Migraine

What is the impact of migraine beyond the headache?

Migraine is more than just a headache. It is a neurologic disorder characterized by moderate to severe head pain that can be exacerbated by movement and frequently accompanied by nausea, vomiting, and disruption of daily activities.^1,2

Explore this website to understand the current findings on the pathophysiology underlying this disease and how it may impact the clinical management of patients with migraine.³

Migraine Burden of Disease

Find data and expert insights illustrating the burden that patients with migraine can experience over time. Check out the Interactive Migraine Disability Calculator

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Diagnosis and Management

Find migraine diagnosis criteria, management options, and preventive treatment information in accordance with AHS and IHS guidelines

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CGRP and Migraine Pathophysiology

See the clinical evidence that demonstrates the role that CGRP signaling may play in the pathophysiology of migraine

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Resource Library

Read, download, watch, and interact with a library of resources covering the burden of migraine, diagnosis guidelines, and more

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AHS, American Headache Society; CGRP, calcitonin gene-related peptide; IHS, International Headache Society.

REFERENCES

It is one of the most prevalent neurological disorders, affecting more than ten percent of people worldwide,^1-4 and one of the most common reasons people consult a doctor.⁵ The impact of this debilitating disease is significant, yet it remains under-recognized and undertreated.^6-9 It is migraine and it is among the leading causes of years lived with disability.^3,10 Migraine is a complex neurological disease characterized by recurrent headaches and associated symptoms. Headaches can be incapacitating and vary in frequency.^11,12 Women are two to three times more likely than men to be affected5 and migraine may have a genetic component.^5,11,13 As a migraine attack progresses, patients can experience a range of symptoms, especially sensory disturbances and pain.^11,12,14-23 Research continues to reveal a complex pathophysiology underlying migraine that involves multiple processes in both the central nervous system, or CNS, and in the periphery.^6,24 These may include neuropeptide release¹¹, neurogenic inflammation,^11,25 vasodilation, stimulation of sensory neurons11 and the activation of specific regions within the brain and brainstem.¹⁴ Researchers have yet to determine which of these processes play a causal role, or if they occur as a result of or in parallel with migraine.^11,14 In addition, it has been proposed that feedback from a hypersensitized brain may further exacerbate pain signaling.^11,25 Despite what we know of migraine pathophysiology, the roles played by central and peripheral processes in migraine are not yet fully understood. Nonetheless, one particular neuropeptide has been shown to play an important role in migraine pathogenesis. Calcitonin gene-related peptide, or CGRP,^1,11,25 is expressed within the trigeminal pathway,^1,25 a neurovascular system with components located both centrally and in the periphery.^25,26 In contrast with other neuropeptides, CGRP levels have been shown to increase during migraine^27,28 and are reduced with headache relief.^11,25,28,29 As well, experimental intravenous infusion of CGRP induces migraine-like headache in patients,^11,14,30,31 suggesting that CGRP may play a causal role in migraine.^20,30,31 The CGRP receptor is a complex of calcitonin receptor-like receptor, receptor activity modifying protein 1, and receptor component protein.^11,25 CGRP receptors are localized at several sites within the trigeminovascular pathway, including the trigeminal ganglion and brainstem.^26,32 The interaction of CGRP with CGRP receptors within the trigeminovascular pathway is believed to contribute to migraine pathophysiology. In the periphery, the binding of CGRP to its receptor on vascular smooth muscle can lead to the dilation of cerebral and meningeal blood vessels.¹¹ The activation of nociceptive trigeminal neurons relays the migraine pain signal through the brainstem into the CNS, ultimately leading to the experience of migraine pain.¹¹ CGRP receptor signaling at sites within the CNS may have numerous effects including central sensitization¹¹ and exacerbation of pain signals¹⁰, which contributes to11 common migraine symptoms.^11,16 Central processes can also lead to migraine pain signaling and activation of other pathways within the brain.^11,24 The important role of CGRP in migraine pathogenesis is of great interest to researchers in their quest to understand more about this common disabling disease.²⁵

References

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Bigal M, et al. Neurology. 2008;71:559-566.
Diamond S, et al. Headache. 2007;47:355-363.
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