Inflammation is a key component of migraine, and can be observed in the trigeminal nerve and associated vasculature.
As the theory of what causes migraine has evolved, it is easy to neglect the fact that inflammation has always been seen as a key component of migraine pathology, regardless of whether the emphasis was on the blood vessels or the nerves.
The theory on the mechanism of action by which triptans work has also changed over the years. At first they were believed to work (and were in fact designed to work) primarily by constricting the vessels – as vessel dilation was believed to be the source of pain in migraine.
More recently the triptans have been deemed to work by inhibiting the release of CGRP, and a new generation of CGRP inhibitors have been under development for some time. CGRP is a pro-inflammatory neuropeptide. To that extent, understanding of migraine pathology has again returned to inflammation.
In any case, ‘leaky’ blood vessels (plasma protein extravasation) are associated with migraine. Both the ergots and the triptans reduce extravasation.
While the publication briefly summarized below is somewhat dated, it nonetheless suggests inflammation, affecting the vessels, mediated through the trigeminal nerve – all of which is consistent with present day understanding of migraine, despite any change in ’emphasis’ – past or present.
Migraine always has been and always will be a disease closely associated with inflammation.
The trigemino-vascular system and migraine.
Summary of the abstract
Neurogenic inflammation has been proposed as a possible pathogenic mechanism for migraine.
Stimulation of trigeminal fibers causes plasma protein extravasation, mast cell activation and other inflammation-related changes.
The antimigraine drugs sumatriptan and dihydroergotamine block the development of plasma extravasation and ultrastructural changes, as well as plasma calcitonin gene-related peptide increase.
Sumatriptan and dihydroergotamine bind with high affinity to the serotonin receptors, thus suggesting that their neurogenic anti-inflammatory activity is mediated by activation of receptors present on sensory fibers innervating blood vessels in the brain.