Why does the brain choose pain? Why does an organ that is able to mask pain, even when intense as in fractures or in fighting wounds, decide to let pain pass and begin conscious, such as that of migraine, when there is no noxa patogena and there is no threat to the integrity of the organism, failing in the main function of pain, that of protection? In this brief review, we retrace the journey that led to the identification of the first complex mechanism of regulation of painful input, the spinal gate control system, through the identification of the predominantly thalamocortical supraspinal centers of the neuromatrix, up to the recognition of a pain matrix extremely articulate and sophisticated that integrates elementary sensations with much more complex functions, related to memory, affectivity, emotion, autonomic self-regulation, and homeostasis systems and so on. Why does the protection system lose its fundamental function in migraine in a behavioral harakiri that periodically damages only itself? This is the challenge facing those dealing with primary headaches in the next future: why migraine? The great strides made in the last decades that have led to the understanding of complex pathogenetic mechanisms risk remaining orphans if we fail to identify the primum movens at the base of one of the most common pathologies in the human race.
Keywords: Gate control system; Headache; Migraine; Pain; Pain matrix.