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Hallmarks of primary headache: part 3 - cluster headache

2025-12-01Review article Open access
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dc.contributor.authorCoppola, Gianluca
dc.contributor.authorArruda, Marco Antônio
dc.contributor.authorAshina, Messoud
dc.contributor.authorBarloese, Mads
dc.contributor.authorBelin, Andrea Carmine
dc.contributor.authorBottiroli, Sara
dc.contributor.authorChowdhury, Debashish
dc.contributor.authorIcco, Roberto De
dc.contributor.authorLorenzo, Cherubino di
dc.contributor.authorStefano, Giulia Di
dc.contributor.authorEdvinsson, Jacob C. A.
dc.contributor.authorEvers, Stefan
dc.contributor.authorFerraro, Stefania
dc.contributor.authorFronczek, Rolf
dc.contributor.authorGarcía-Azorín, David
dc.contributor.authorGoadsby, Peter J.
dc.contributor.authorGrazzi, Licia
dc.contributor.authorHolle, Dagny
dc.contributor.authorJansen, Julia J.
dc.contributor.authorGil-Gouveia, Raquel
dc.contributor.authorLambru, Giorgio
dc.contributor.authorLanteri-Minet, Michel
dc.contributor.authorLisicki, Marco
dc.contributor.authorMitsikostas, Dimos D.
dc.contributor.authorMonteith, Teshamae
dc.contributor.authorMontisano, Danilo Antonio
dc.contributor.authorObermann, Mark
dc.contributor.authorPan, Li Ling Hope
dc.contributor.authorPeng, Kuan Po
dc.contributor.authorPeres, Mario
dc.contributor.authorPetrušic, Igor
dc.contributor.authorCecchini, Alberto Proietti
dc.contributor.authorVila-Pueyo, Marta
dc.contributor.authorRaggi, Alberto
dc.contributor.authorRainero, Innocenzo
dc.contributor.authorSandrini, Giorgio
dc.contributor.authorSebastianelli, Gabriele
dc.contributor.authorTakizawa, Tsubasa
dc.contributor.authorTanprawate, Surat
dc.contributor.authorTassorelli, Cristina
dc.contributor.authorTruini, Andrea
dc.contributor.authorValeriani, Massimiliano
dc.contributor.authorVuralli, Doga
dc.contributor.authorWaliszewska-Prosół, Marta
dc.contributor.authorWang, Shuu Jiun
dc.contributor.authorWang, Yonggang
dc.contributor.authorWijeratne, Tissa
dc.contributor.authorMartelletti, Paolo
dc.date.accessioned2025-10-20T11:10:32Z
dc.date.available2025-10-20T11:10:32Z
dc.date.issued2025-12-01
dc.description.abstractBackground: Cluster headache (CH) is a rare primary headache disorder characterized by recurrent episodes of strictly unilateral excruciating pain accompanied by trigemino-autonomic signs, which significantly impacts the quality of life, social interactions, and occupational functioning of those who are affected. To promote a better understanding of this disabling condition and to foster research on the topic, this review provides a comprehensive description of the hallmarks of CH, including its clinical presentation, diagnostic challenges, pathophysiology, and current and novel therapeutic targets. It concludes by describing the disease burden and advocating for significant improvements in healthcare systems, and promoting health equity, as well as reducing stigma. Principal findings: Despite its distinctive clinical and chronobiological features, CH may be mistaken for other primary headache disorders or different types of orofacial pain. Key pathogenic characteristics include the activation of the trigeminal-autonomic system with the release of several neuropeptides, the involvement of the hypothalamus in regulating the circadian rhythm, genetic variants, and the mesolimbic system. Both invasive and non-invasive neuromodulation treatments have been used to target the trigemino-cervical, parasympathetic, and hypothalamic systems. Additionally, novel therapeutic targets are currently being study. Alongside canonical therapies, several complementary approaches have been explored over the years, with most evidence deriving from uncontrolled research involving individuals who do not respond to standard pharmacological treatments. Despite advancements in our understanding of this complex disease, CH continues to pose considerable social, economic, and psychological challenges. Advocacy is essential and should prioritize early diagnosis, alleviate stigma, provide specialized training for healthcare professionals, and offer support to and through patient associations. Conclusions: CH is characterised by a complex, multifactorial, pathophysiology that is still not fully understood. Precise diagnosis, additional research studies, and robust psychosocial and institutional support are necessary to improve the quality of life for individuals affected by this debilitating condition.eng
dc.identifier.citationCoppola, G., Arruda, M. A., Ashina, M., & Barloese, M. et al. (2025). Hallmarks of primary headache: part 3 - cluster headache. Journal of Headache and Pain, 26(1), Article 196. https://doi.org/10.1186/s10194-025-02145-6
dc.identifier.doi10.1186/s10194-025-02145-6
dc.identifier.eid105017644484
dc.identifier.issn1129-2369
dc.identifier.otherbe281295-602f-4fb4-b46e-902268ed5574
dc.identifier.pmcPMC12490097
dc.identifier.pmid41039211
dc.identifier.urihttp://hdl.handle.net/10400.14/55399
dc.identifier.wos001586943400004
dc.language.isoeng
dc.peerreviewedyes
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAdvocacy
dc.subjectCircadian rhythm
dc.subjectHypothalamus
dc.subjectNeuromodulation
dc.subjectNeuropeptides
dc.subjectPrimary headache
dc.subjectPsychological factors
dc.subjectTreatments
dc.subjectTrigeminal-autonomic system
dc.titleHallmarks of primary headache: part 3 - cluster headacheeng
dc.typereview article
dspace.entity.typePublication
oaire.citation.issue1
oaire.citation.titleJournal of Headache and Pain
oaire.citation.volume26
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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