Rationale for Correct Answer

The correct answer is: It promotes neuroinflammation and peripheral and central neuronal sensitization

The aura associated with migraine is thought to be the consequence of cortical spreading depolarization, a wave of electrical activity passing over the outer layer of the brain. This phenomenon, along with changes in blood flow and cerebral brain activity, activates the trigeminovascular system and alters blood-brain barrier permeability.1,2

The peripheral trigeminovascular system, extending from the brainstem trigeminal nuclei to meningeal blood vessels, includes a rich plexus of nociceptive nerve fibers originating in the trigeminal nerve ganglion that innervates the meningeal blood vessels. Activating these nerve fibers triggers meningeal inflammation, manifesting as headache, nausea, and photophobia.1

The axon terminals of nociceptive nerve fibers in the trigeminal nerve ganglion contain vasoactive neuropeptides, such as CGRP, substance P, neurokinin A, and pituitary adenylate cyclase-activating peptide. Release of these neuropeptides causes vasodilation in dural and pial vessels, mast cell degranulation, activation of nociceptors, and plasma protein extravasation,1,2 contributing to neurogenic inflammation and prolonged migraine pain.2

Fibers from the upper cervical nerve roots and the trigeminal nerve converge at the trigeminal nucleus caudalis as part of the central trigeminovascular system. These fibers convey pain signals from the trigeminal nucleus caudalis to the thalamus and cerebral cortex.3

Elevated CGRP levels play an important role in triggering migraine attacks.4 However, the role of serotonin in migraine generation is unclear. Serotonin receptor agonists, such as triptans, mitigate migraine symptoms by countering CGRP-induced vasodilation, reducing CGRP release by activating 5-HT1 receptors, and providing pain relief.5

1. Goadsby PJ, et al. Physiol Rev. 2017;97(2):553-622;
2. Dodick DW. Headache. 2018;58 Suppl 1:4-16;
3. Raddant AC, et al. Expert Rev Mol Med. 2011;13:e36;
4. Wattiez AS, et al. Expert Opin Ther Targets. 2020;24(2):91-100;
5. Aggarwal M, et al. Ann Neurosci. 2012;19(2):88-94.