Clinical meaning
Migraine, tension-type headache, and cluster headache arise from distinct pathophysiological mechanisms despite overlapping symptom features. Migraine involves activation of the trigeminovascular system with cortical spreading depression triggering release of CGRP from trigeminal perivascular nerve endings, producing meningeal neurogenic inflammation, pulsating unilateral pain, and central sensitization that manifests as photophobia, phonophobia, and cutaneous allodynia. Nausea results from activation of the nucleus tractus solitarius and area postrema via trigeminal afferents. Tension-type headache (TTH), the most prevalent primary headache, involves peripheral myofascial mechanisms in episodic forms (sustained contraction and sensitization of pericranial muscles producing bilateral pressing or band-like pain) and central sensitization of supraspinal pain pathways in chronic forms, where reduced descending inhibition from the periaqueductal gray and rostroventral medulla lowers pain thresholds. TTH notably lacks the nausea, photophobia, and phonophobia characteristic of migraine. Cluster headache is classified among the trigeminal autonomic cephalalgias (TACs), characterized by activation of the trigeminal-autonomic reflex arc. The hypothalamus serves as the primary generator, evidenced by PET imaging showing posterior hypothalamic activation during attacks and explaining the striking circadian and circannual periodicity. Trigeminal nociceptive activation causes excruciating strictly...