Clinical meaning
Primary headaches are disorders in themselves without an underlying structural or systemic cause, classified by the ICHD-3 (International Classification of Headache Disorders). Migraine pathophysiology involves cortical spreading depression (CSD) — a self-propagating wave of neuronal and glial depolarization spreading across the cortex at 3-5 mm/min, followed by sustained suppression of neural activity. CSD activates trigeminal sensory afferents innervating the meninges, releasing vasoactive neuropeptides (CGRP, substance P, neurokinin A) that cause neurogenic inflammation, meningeal vasodilation, and mast cell degranulation. The trigeminal nucleus caudalis in the brainstem receives and amplifies these pain signals, producing the characteristic throbbing unilateral headache. Central sensitization develops when repeated trigeminal activation lowers the pain threshold, causing allodynia (pain from normally non-painful stimuli like brushing hair). Secondary headaches are symptomatic of an underlying condition — the headache is a symptom, not the disease. Key secondary causes include subarachnoid hemorrhage (sudden severe headache from ruptured berry aneurysm), meningitis/encephalitis (headache with fever, neck stiffness, altered mental status), space-occupying lesions (progressive headache worse in morning, with focal deficits), giant cell arteritis (new headache in patient >50 with elevated ESR, jaw claudication,...