Hallmarks of primary headache : part 3 - cluster headache
(2025) In Journal of Headache and Pain 26. p.1-61- Abstract
BACKGROUND: 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... (More)
BACKGROUND: 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.
(Less)
- author
- organization
- publishing date
- 2025-10-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Humans, Cluster Headache/diagnosis
- in
- Journal of Headache and Pain
- volume
- 26
- article number
- 196
- pages
- 1 - 61
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:105017644484
- pmid:41039211
- ISSN
- 1129-2369
- DOI
- 10.1186/s10194-025-02145-6
- language
- English
- LU publication?
- yes
- additional info
- © 2025. The Author(s).
- id
- 682b955c-5d0f-481d-aa0c-e6018d408f19
- date added to LUP
- 2025-10-27 09:33:27
- date last changed
- 2025-10-28 04:01:04
@article{682b955c-5d0f-481d-aa0c-e6018d408f19,
abstract = {{<p>BACKGROUND: 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.</p><p>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.</p><p>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.</p>}},
author = {{Coppola, Gianluca and Arruda, Marco Antônio and Ashina, Messoud and Barloese, Mads and Belin, Andrea Carmine and Bottiroli, Sara and Chowdhury, Debashish and De Icco, Roberto and Di Lorenzo, Cherubino and Di Stefano, Giulia and Edvinsson, Jacob C A and Evers, Stefan and Ferraro, Stefania and Fronczek, Rolf and García-Azorín, David and Goadsby, Peter J and Grazzi, Licia and Holle, Dagny and Jansen, Julia J and Gil-Gouveia, Raquel and Lambru, Giorgio and Lanteri-Minet, Michel and Lisicki, Marco and Mitsikostas, Dimos D and Monteith, Teshamae and Montisano, Danilo Antonio and Obermann, Mark and Pan, Li-Ling Hope and Peng, Kuan-Po and Peres, Mario and Petrušić, Igor and Cecchini, Alberto Proietti and Vila-Pueyo, Marta and Raggi, Alberto and Rainero, Innocenzo and Sandrini, Giorgio and Sebastianelli, Gabriele and Takizawa, Tsubasa and Tanprawate, Surat and Tassorelli, Cristina and Truini, Andrea and Valeriani, Massimiliano and Vuralli, Doga and Waliszewska-Prosół, Marta and Wang, Shuu-Jiun and Wang, Yonggang and Wijeratne, Tissa and Martelletti, Paolo}},
issn = {{1129-2369}},
keywords = {{Humans; Cluster Headache/diagnosis}},
language = {{eng}},
month = {{10}},
pages = {{1--61}},
publisher = {{BioMed Central (BMC)}},
series = {{Journal of Headache and Pain}},
title = {{Hallmarks of primary headache : part 3 - cluster headache}},
url = {{http://dx.doi.org/10.1186/s10194-025-02145-6}},
doi = {{10.1186/s10194-025-02145-6}},
volume = {{26}},
year = {{2025}},
}