Clinical meaning
Primary headache disorders involve dysfunction of pain-processing pathways without structural pathology. Migraine pathophysiology centers on trigeminovascular system activation: cortical spreading depression (a wave of neuronal depolarization followed by suppression) triggers the aura phase and activates trigeminal nerve afferents innervating meningeal blood vessels. Activated trigeminal fibres release calcitonin gene-related peptide (CGRP), substance P, and neurokinin A, causing neurogenic inflammation, vasodilation, and meningeal sensitization. Central sensitization of the trigeminal nucleus caudalis produces cutaneous allodynia. Serotonin (5-HT1B/1D) receptors on trigeminal terminals and meningeal vessels are the targets of triptans, which inhibit CGRP release and cause meningeal vasoconstriction. Tension-type headache involves peripheral myofascial nociception from pericranial muscles with central pain modulation dysfunction in chronic forms. Cluster headache involves hypothalamic activation with parasympathetic outflow through the sphenopalatine ganglion causing unilateral autonomic symptoms (lacrimation, rhinorrhea, conjunctival injection).