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Review
. 2025 Mar 21;14(7):2160.
doi: 10.3390/jcm14072160.

Cluster Headache and Migraine Shared and Unique Insights: Neurophysiological Implications, Neuroimaging, and Biomarkers: A Comprehensive Review

Gabriele Bertotti  1   2 , Vicente Fernández-Ruiz  1 , Alberto Roldán-Ruiz  1 , Miguel López-Moreno  1
Affiliations
Review

Cluster Headache and Migraine Shared and Unique Insights: Neurophysiological Implications, Neuroimaging, and Biomarkers: A Comprehensive Review

Gabriele Bertotti et al. J Clin Med. .

Abstract

Migraine headache (MH) and cluster headache (CH) are debilitating primary headache disorders that impose a significant global burden. While they share certain clinical features, such as unilateral pain and autonomic dysfunction, their underlying pathophysiological mechanisms remain distinct. Advances in the understanding of neurophysiological features, such as neuroimaging and biomarker research, have provided critical insights into both their overlapping and divergent characteristics. Neurophysiological research has revealed differences in nociceptive processing, cortical excitability, and sensory integration, underscoring the complexity of these conditions. Neuroimaging studies reveal common activation patterns within pain-processing networks, including the trigeminal system and hypothalamus, while highlighting key differences, such as hypothalamic hyperactivity in CH and cortical alterations in MH. Additionally, biomarker research has identified shared elements, including elevated calcitonin gene-related peptide (CGRP), yet distinct variations in its regulation and genetic predispositions. Genome-wide association studies have further elucidated the genetic architecture of these disorders, uncovering susceptibility loci that reinforces their unique yet occasionally intersecting genetic foundations. These multifield advancements not only enhance the understanding of MH and CH pathophysiology but also pave the way for improved diagnostic precision, personalized therapeutic strategies, and future research.

Keywords: biomarker; chronic pain; cluster headache; migraine; neuroimaging; neurophysiology; pathophysiology.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of the trigemino-autonomic reflex. TG: trigeminal ganglion. SPG: sphenopalatine ganglion. SSN: superior salivary nucleus. TNC: trigeminal nucleus caudalis. Edited with biorender.com.
Figure 2
Figure 2
Summaries of shared and unique insights in cluster headache and in migraine headache. Edited with biorender.com.
See this image and copyright information in PMC

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References

    1. Dodick D., Edvinsson L., Makino T., Grisold W., Sakai F., Jensen R., Balch A., Ruiz de la Torre E., Henscheid-Lorenz D., Craven A., et al. Vancouver Declaration on Global Headache Patient Advocacy 2018. Cephalalgia. 2018;38:1899–1909. doi: 10.1177/0333102418781644. - DOI - PubMed
    1. Zhang Y.J., Li X.Y., Guo Z.L. Temporal Trends of Migraine and Tension-Type Headache Burden across the BRICS: Implications from the Global Burden of Disease Study 2019. Front. Neurol. 2023;14:1307413. doi: 10.3389/FNEUR.2023.1307413. - DOI - PMC - PubMed
    1. May A., Schwedt T.J., Magis D., Pozo-Rosich P., Evers S., Wang S.J. Cluster Headache. Nat. Rev. Dis. Primers. 2018;4:18006. doi: 10.1038/nrdp.2018.6. - DOI - PubMed
    1. Steiner T.J., Stovner L.J., Jensen R., Uluduz D., Katsarava Z. Migraine Remains Second among the World’s Causes of Disability, and First among Young Women: Findings from GBD2019. J. Headache Pain. 2020;21:137. doi: 10.1186/S10194-020-01208-0. - DOI - PMC - PubMed
    1. Ji Lee M., Cho S.J., Wook Park J., Kyung Chu M., Moon H.S., Chung P.W., Myun Chung J., Sohn J.H., Kim B.K., Kim B.S., et al. Increased Suicidality in Patients with Cluster Headache. Cephalalgia. 2019;39:1249–1256. doi: 10.1177/0333102419845660. - DOI - PubMed

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