The attack is thought to be related to an activation of the trigemino-vascular system, which innervates the dura mater and the cranial vessels.
There is reflex activation via the facial nerve, with a relay in the sphenopalatin ganglion, which increases vasodilatation and causes irritation of the trigeminal endings. This activation of the autonomic nervous system is notably the cause of the symptoms accompanying the attack (tearing, conjunctival injection, nasal congestion, …).
This phenomenon is probably due, at least in part, to a dysfunction of the hypothalamus, an organ involved in multiple vital functions. The dysregulation appears to be located in the region of the hypothalamus regulating in particular the circadian and circannual rhythms and involves a complex set of hormonal interactions. In fact, attacks often return at the same times, and episodes at the same periods of the year.
In addition, a neuropeptide, the CGRP (calcitonin gene related peptide) also seems to be involved in the attacks.
This peptide has, among other things, a vasodilating action and increases sensitivity to pain at the neuronal level.
But many questions remain unanswered as to the exact course of an attack and the general functioning of this disease.