Figure 1.

Migraine pain origin, transmission and perception. Migraine related nociceptive signalling originates in the trigeminovascular system (TGVS) composed of the trigeminal ganglia (TG), nociceptive Aδ- and C-fibres projecting to meninges, dural mast cells and the local vasculature. These structures can interact with each other via chemical or mechanical communications forming a vicious circle, which promotes and supports neuroinflammation, activation and sensitization of nociceptors. Nociceptive signalling (red arrows) can be initiated by mechanical forces, from pulsating dural vessels, CSD- or stress-induced degranulation of mast cells or by antidromic spiking directed to the meninges and associated with the release of several neuropeptides including CGRP. Migraine-related nociceptive signalling is transmitted from the meninges through the brainstem (zoomed down in grey box) trigeminal nucleus caudalis (TNC) and thalamus (purple), to the higher pain centres in the cortex performing the function of pain perception. Opposite to the ascending nociceptive signalling, the descending inhibitory control of the brainstem provides the anti-nociceptive function (dark grey arrow). A migraine attack can start with cortical spreading depression (CSD), a phenomenon typical for migraine with aura with massive depolarization of neurons and glial cells slowly propagating along the cortex.