Migraine and cluster headache – the common link

Abstract

Although clinically distinguishable, migraine and cluster headache share prominent features such as unilateral pain, common pharmacological triggers such glyceryl trinitrate, histamine, calcitonin gene-related peptide (CGRP) and response to triptans and neuromodulation. Recent data also suggest efficacy of anti CGRP monoclonal antibodies in both migraine and cluster headache. While exact mechanisms behind both disorders remain to be fully understood, the trigeminovascular system represents one possible common pathophysiological pathway and network of both disorders. Here, we review past and current literature shedding light on similarities and differences in phenotype, heritability, pathophysiology, imaging findings and treatment options of migraine and cluster headache. A continued focus on their shared pathophysiological pathways may be important in paving future treatment avenues that could benefit both migraine and cluster headache patients.

CGRP and the Trigeminal System in Migraine

“…Likewise, imaging studies have also shown that the hypothalamic nuclei are activated during the pain phase of cluster headache attacks . The cyclic nature and circadian predictability of cluster headache is consistent with the pacemaking functions of hypothalamic nuclei …”

Targeting CGRP for the Prevention of Migraine and Cluster Headache: A Narrative Review

“…Migraine and cluster headache (CH), though clinically distinguishable by ICHD‐3 criteria, share a common pathophysiology: the trigeminovascular pathway . Trigeminal afferents are pseudo‐unipolar neurons with cell bodies forming the trigeminal ganglion (TG) where neurons interact with the surrounding satellite glial cells and other cell types .…”

“…Great challenges remain in managing migraine and CH, since these are complex neurovascular pain syndromes. Based on the attack frequency or cluster period, migraine and CH can be categorized as episodic or chronic . Many clinically effective preventive medications are used off‐label and each demonstrates a unique adverse effect (AE) profile, possibly impacting medication adherence and leading to headache chronification.…”

“…Migraine and cluster headache (CH), though clinically distinguishable by ICHD-3 criteria, 1 share a common pathophysiology: the trigeminovascular pathway. 2 Trigeminal afferents are pseudo-unipolar neurons with cell bodies forming the trigeminal ganglion (TG) where neurons interact with the surrounding satellite glial cells and other cell types. 3 These afferents (primarily ophthalmic branch) innervate pain-sensitive structures in the head and send sensory signals to trigeminal cervical complex (TCC), which then projects to multiple nuclei (eg, thalamus, hypothalamus, brainstem, basal ganglia) involved in processing head pain and associated symptoms.…”

“…Based on the attack frequency or cluster period, migraine and CH can be categorized as episodic or chronic. 2 Many clinically effective preventive medications are used off-label and each demonstrates a unique adverse effect (AE) profile, possibly impacting medication adherence and leading to headache chronification. Historically, preventive medications used in migraine and CH management have been initially designed for other medical conditions (eg, hypertension, epilepsy, depression, etc.)…”