Review

. 2025 Oct 2;26(1):196.

doi: 10.1186/s10194-025-02145-6.

Hallmarks of primary headache: part 3 - cluster headache

Gianluca Coppola¹, Marco Antônio Arruda², Messoud Ashina^{3

4}, Mads Barloese^{3

5}, Andrea Carmine Belin⁶, Sara Bottiroli^{7

8}, Debashish Chowdhury⁹, Roberto De Icco^{7

8}, Cherubino Di Lorenzo¹⁰, Giulia Di Stefano¹¹, Jacob C A Edvinsson¹², Stefan Evers^{13

14}, Stefania Ferraro¹⁵, Rolf Fronczek^{16

17}, David García-Azorín^{18

19}, Peter J Goadsby^{20

21}, Licia Grazzi²², Dagny Holle²³, Julia J Jansen^{24

25}, Raquel Gil-Gouveia^{26

27}, Giorgio Lambru^{28

29}, Michel Lanteri-Minet^{30

31}, Marco Lisicki^{32

33}, Dimos D Mitsikostas³⁴, Teshamae Monteith³⁵, Danilo Antonio Montisano²², Mark Obermann³⁶, Li-Ling Hope Pan³⁷, Kuan-Po Peng³⁸, Mario Peres³⁹, Igor Petrušić⁴⁰, Alberto Proietti Cecchini²², Marta Vila-Pueyo⁴¹, Alberto Raggi⁴², Innocenzo Rainero⁴³, Giorgio Sandrini⁷, Gabriele Sebastianelli¹⁰, Tsubasa Takizawa⁴⁴, Surat Tanprawate⁴⁵, Cristina Tassorelli^{7

8}, Andrea Truini¹¹, Massimiliano Valeriani^{46

47}, Doga Vuralli⁴⁸, Marta Waliszewska-Prosół⁴⁹, Shuu-Jiun Wang^{37

50

51}, Yonggang Wang⁵², Tissa Wijeratne⁵³, Paolo Martelletti⁵⁴

Affiliations

¹ Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Via Franco Faggiana, Latina, 1668 - 04100, Italy. gianluca.coppola@uniroma1.it.
² Glia Institute, Ribeirão Preto, SP, Brazil.
³ Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
⁴ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁵ Department for Functional and Diagnostic Imaging, Amager and Hvidovre University Hospital, Copenhagen, Denmark.
⁶ Centre for Cluster Headache, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁷ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
⁸ Headache Science and Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy.
⁹ GB Pant Institute of Postgraduate Medical Education and Research, New Delhi, India.
¹⁰ Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Via Franco Faggiana, Latina, 1668 - 04100, Italy.
¹¹ Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy.
¹² Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.
¹³ Faculty of Medicine, University of Münster, Münster, Germany.
¹⁴ Department of Neurology, Lindenbrunn Hospital, Coppenbrügge, Germany.
¹⁵ Ministry of Education Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology, Chengdu, China.
¹⁶ Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
¹⁷ Stichting Epilepsie Instellingen Nederland (SEIN), Sleep-Wake Centre, Heemstede, the Netherlands.
¹⁸ Department of Neurology, Hospital Universitario del Rio Hortega, Valladolid, Spain.
¹⁹ Department of Medicine, Dermatology and Toxicology, Faculty of Medicine, University of Valladolid, Valladolid, Spain.
²⁰ NIHR King's Clinical Research Facility, King's College, London, UK.
²¹ Department of Neurology, University of California, Los Angeles, CA, USA.
²² Headache Center, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
²³ Department of Neurology, West German Headache and Vertigo Center, Essen University Hospital (AöR), Essen, Germany.
²⁴ Department of Neurology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands.
²⁵ Department of Pharmacy, Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
²⁶ Neurology Department, Hospital da Luz Lisboa, Lisboa, Portugal.
²⁷ Center for Interdisciplinary Research in Health, Universidade Católica Portuguesa, Lisboa, Portugal.
²⁸ Headache and Facial Pain Service, Guy's and St Thomas' Hospital, London, UK.
²⁹ Wolfson Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
³⁰ Département Douleur, FHU InovPain, UR2CA, Centre Hospitalier Universitaire de Nice - Université Côte Azur, Nice, France.
³¹ INSERM U1107 Migraine and Trigeminal Pain, Université Clermont-Auvergne, Clermont-Ferrand, France.
³² Headache Research Laboratory, Mercedes & Martín Ferreyra Institute, National Scientific and Technical Research Council (CONICET), National University of Córdoba, Cordoba, Argentina.
³³ Biomedical Physics Department, School of Medicine, National University of Córdoba (UNC), Córdoba, Argentina.
³⁴ Neurology Department, Aeginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
³⁵ Department of Neurology - Headache Division, Miller School of Medicine, University of Miami, Miami, FL, USA.
³⁶ Department of Neurology, Klinikum Weser-Egge, Höxter, Germany.
³⁷ Brain Research Center, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
³⁸ Department of Systems Neuroscience, University Medical Center- Hamburg Eppendorf, Hamburg, Germany.
³⁹ Hospital Israelita Albert Einstein, , Instituto de Psiquiatria, HCFMUSP, Sao Paulo, Brazil.
⁴⁰ Laboratory for Advanced Analysis of Neuroimages, Faculty of Physical Chemistry, University of Belgrade, Belgrade, Serbia.
⁴¹ Headache and Neurological Pain Research Group, Vall d'Hebron Research Institute (VHIR), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
⁴² 41. Neurology, Public Health and Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
⁴³ Headache Center, Department of Neuroscience "Rita Levi Montalcini", University of Torino, Turin, Italy.
⁴⁴ Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
⁴⁵ The Northern Neuroscience Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
⁴⁶ Developmental Neurology Unit, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
⁴⁷ Systems Medicine Department, Tor Vergata University of Rome, Rome, Italy.
⁴⁸ Department of Neurology and Algology, Neuroscience and Neurotechnology Center of Excellence (NÖROM), Neuropsychiatry Center, Gazi University Faculty of Medicine, Ankara, Turkey.
⁴⁹ Department of Neurology, Wroclaw Medical University, Wroclaw, Poland.
⁵⁰ College of Medicine, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
⁵¹ Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
⁵² Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁵³ Department of Neurology, Department of Medicine, Melbourne Medical School, Sunshine Hospital, Western Health, St Albans, Australia.
⁵⁴ School of Health, Unitelma Sapienza University of Rome, Rome, Italy.

PMID: 41039211
PMCID: PMC12490097
DOI: 10.1186/s10194-025-02145-6

Review

Hallmarks of primary headache: part 3 - cluster headache

Gianluca Coppola et al. J Headache Pain. 2025.

. 2025 Oct 2;26(1):196.

doi: 10.1186/s10194-025-02145-6.

Authors

Affiliations

¹ Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Via Franco Faggiana, Latina, 1668 - 04100, Italy. gianluca.coppola@uniroma1.it.
² Glia Institute, Ribeirão Preto, SP, Brazil.
³ Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
⁴ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁵ Department for Functional and Diagnostic Imaging, Amager and Hvidovre University Hospital, Copenhagen, Denmark.
⁶ Centre for Cluster Headache, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁷ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
⁸ Headache Science and Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy.
⁹ GB Pant Institute of Postgraduate Medical Education and Research, New Delhi, India.
¹⁰ Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Via Franco Faggiana, Latina, 1668 - 04100, Italy.
¹¹ Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy.
¹² Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.
¹³ Faculty of Medicine, University of Münster, Münster, Germany.
¹⁴ Department of Neurology, Lindenbrunn Hospital, Coppenbrügge, Germany.
¹⁵ Ministry of Education Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology, Chengdu, China.
¹⁶ Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
¹⁷ Stichting Epilepsie Instellingen Nederland (SEIN), Sleep-Wake Centre, Heemstede, the Netherlands.
¹⁸ Department of Neurology, Hospital Universitario del Rio Hortega, Valladolid, Spain.
¹⁹ Department of Medicine, Dermatology and Toxicology, Faculty of Medicine, University of Valladolid, Valladolid, Spain.
²⁰ NIHR King's Clinical Research Facility, King's College, London, UK.
²¹ Department of Neurology, University of California, Los Angeles, CA, USA.
²² Headache Center, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
²³ Department of Neurology, West German Headache and Vertigo Center, Essen University Hospital (AöR), Essen, Germany.
²⁴ Department of Neurology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands.
²⁵ Department of Pharmacy, Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
²⁶ Neurology Department, Hospital da Luz Lisboa, Lisboa, Portugal.
²⁷ Center for Interdisciplinary Research in Health, Universidade Católica Portuguesa, Lisboa, Portugal.
²⁸ Headache and Facial Pain Service, Guy's and St Thomas' Hospital, London, UK.
²⁹ Wolfson Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
³⁰ Département Douleur, FHU InovPain, UR2CA, Centre Hospitalier Universitaire de Nice - Université Côte Azur, Nice, France.
³¹ INSERM U1107 Migraine and Trigeminal Pain, Université Clermont-Auvergne, Clermont-Ferrand, France.
³² Headache Research Laboratory, Mercedes & Martín Ferreyra Institute, National Scientific and Technical Research Council (CONICET), National University of Córdoba, Cordoba, Argentina.
³³ Biomedical Physics Department, School of Medicine, National University of Córdoba (UNC), Córdoba, Argentina.
³⁴ Neurology Department, Aeginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
³⁵ Department of Neurology - Headache Division, Miller School of Medicine, University of Miami, Miami, FL, USA.
³⁶ Department of Neurology, Klinikum Weser-Egge, Höxter, Germany.
³⁷ Brain Research Center, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
³⁸ Department of Systems Neuroscience, University Medical Center- Hamburg Eppendorf, Hamburg, Germany.
³⁹ Hospital Israelita Albert Einstein, , Instituto de Psiquiatria, HCFMUSP, Sao Paulo, Brazil.
⁴⁰ Laboratory for Advanced Analysis of Neuroimages, Faculty of Physical Chemistry, University of Belgrade, Belgrade, Serbia.
⁴¹ Headache and Neurological Pain Research Group, Vall d'Hebron Research Institute (VHIR), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
⁴² 41. Neurology, Public Health and Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
⁴³ Headache Center, Department of Neuroscience "Rita Levi Montalcini", University of Torino, Turin, Italy.
⁴⁴ Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
⁴⁵ The Northern Neuroscience Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
⁴⁶ Developmental Neurology Unit, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
⁴⁷ Systems Medicine Department, Tor Vergata University of Rome, Rome, Italy.
⁴⁸ Department of Neurology and Algology, Neuroscience and Neurotechnology Center of Excellence (NÖROM), Neuropsychiatry Center, Gazi University Faculty of Medicine, Ankara, Turkey.
⁴⁹ Department of Neurology, Wroclaw Medical University, Wroclaw, Poland.
⁵⁰ College of Medicine, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
⁵¹ Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
⁵² Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁵³ Department of Neurology, Department of Medicine, Melbourne Medical School, Sunshine Hospital, Western Health, St Albans, Australia.
⁵⁴ School of Health, Unitelma Sapienza University of Rome, Rome, Italy.

PMID: 41039211
PMCID: PMC12490097
DOI: 10.1186/s10194-025-02145-6

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 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.

Keywords: Advocacy; Circadian rhythm; Hypothalamus; Neuromodulation; Neuropeptides; Primary headache; Psychological factors; Treatments; Trigeminal-autonomic system.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: M.A. Arruda, M. Barloese, A.C. Belin, S. Bottiroli, D. Chowdhury, C. Di Lorenzo, G. Di Stefano, J.C. A. Edvinsson, S. Evers, S. Ferraro, L. Grazzi, D. Holle, J.J. Jansen, M. Lisicki, D. Mitsikostas, M. Obermann, K-P Peng, A. P. Cecchini, M. Vila-Pueyo, I. Rainero, G. Sandrini, S. Tanprawate, and A. Truini declare no competing interest regarding this manuscript. G. Coppola declares to be Associate Editor of The Journal of Headache and Pain, Cephalalgia, Cephalalgia Reports, Frontiers in Neurology (Neurotechnology section), BMC Neurology (Pain section), Frontiers in Human Neuroscience (Brain Imaging and Stimulation section), Headache and Pain Research, Confinia Cephalalgica. He has received honoraria as a moderator from AbbVie, Pfizer, and Eli-Lilly, has received consulting fees from AbbVie, Eli-Lilly, and Pfizer, and has been the PI in trials sponsored by Pfizer and AbbVie. He has received research grants from AbbVie. M. Ashina has received personal fees as a consultant or speaker from AbbVie, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Pfizer, and Teva, outside of the submitted work. MA also serves as an Associate Editor of Brain and an Associate Editor of The Journal of Headache and Pain. R. De Icco is Junior Editor of Cephalalgia. He received speaker honoraria from Eli Lilly, Lundbeck, TEVA, Pfizer and AbbVie outside the submitted work. He participated in advisory boards of Pfizer and AbbVie. He received a research grant by the Italian Ministry of Health. R. Fronczek has received consultancy fees from Teva and Salvia, speaker fees from Novartis and Lundbeck, and grant support from MedTronic; and is associate editor of cephalalgia. D. García-Azorín declares to be Associate Editor of The Journal of Headache and PainP.J. Goadsby reports, over the last 36 months, personal fees for consulting from Aeon Biopharma, Abbvie, Aurene, CoolTech LLC, Dr Reddy’s, Eli-Lilly and Company, Epalex, Ipsen, Kallyope, Linpharma, Lundbeck, Orion Pharma, Pfizer, PureTech Health LLC, Satsuma, Shiratronics, Teva Pharmaceuticals, and Vial. R. Gil-Gouveia reports honoraria from Allergan/Abbvie, Astra Zeneca, Almirall, Bial, Biogen, Bristol-Myers Squibb, CMBE, FLOAT, Lilly, Lundbeck, Merk, Novartis, Novo Nordisk, Organon, Pfizer, Roche, Sanofi, Tecnifar, Teva. G. Lambru: Co‐chair of the Medical Advisory Board of the Trigeminal Neuralgia Association (TNA) UK; received personal fees from Abbvie, Teva, Novartis, Eli Lilly, Lundbeck; Pfizer, Dr Reddy's laboratories. Participated in clinical trials as principal investigator for Novartis, Eli Lilly, Teva, NOEMA. M. Lanteri-Minet declares to be Associate Editor of The Journal of Headache and Pain and reports personal fee for advisory boards, speaker panels or investigation studies from Allergan, Amgen, Astellas, ATI, BMS, Boehringer, Boston Scientific, CoLucid, Convergence, Eli Lilly, GlaxoSmithKline, Grunenthal, Eli Lilly, IPSEN Lundbeck, Medtronic, MSD, Novartis, Perfood, Pfizer, ReckittBenckiser, Saint-Jude, Salvia BioElectronics, Sanofi-Aventis, Teva, UCB, UPSA and Zambon. T. Monteith has the following disclosures over the past three years: clinical trial site principal investigator for studies sponsored by Abbvie, Eli Lilly, Ipsen and Rehaler, participation in advisory board/consultancy for AbbVie, Teva, Linpharma, e-Neura, Lundbeck, Novartis, Axsome, Merz, and Pfizer, Educational grant from Amgen and AbbVie, personal fees from Medscape, Massachusetts Medical Society, American Headache Society, American Academy of Neurology, Neurodiem, Academic CME, AbbVie, Novartis, unpaid co-author for research funded by AbbVie, Pfizer/Biohaven, and Theranica. She is an associate editor for Cephalalgia and Continuum Audio, and is on the editorial board for Neurology, American Migraine Foundation, and Brain and Life Magazine. x has provided unpaid service on the board of directors for the International Headache Society (2021-2023) and currently on the executive board for the Florida Society of Neurology. D.A. Montisano received speaker honoraria from Lundbeck, TEVA and AbbVie outside the submitted work. L.L.H. Pan serves as member of Junior Editorial Board of The Journal of Headache and Pain. M. Peres declares to be Associate Editor of The Journal of Headache and Pain. I. Petrušić serves as member of the Editorial Board of The Journal of Headache and Pain, Head of Imaging Section of the SN Comprehensive Clinical Medicine journal and as the Guest Editor in The Journal of Headache and Pain. A. Raggi declares to be Associate Editor of The Journal of Headache and Pain, and of Head of Public Health Section, SN Comprehensive Clinical Medicine.G. Sebastianelli serves as member of Junior Editorial Board of The Journal of Headache and Pain. T. Takizawa is a consultant/advisor and/or serves on an advisory board for Eli Lilly, Otsuka, Amgen, Pfizer, and Teijin and has received speaker honoraria from Eli Lilly, Daiichi Sankyo, Otsuka, Amgen, Kowa, Kyowa Kirin, Eisai, UCB Japan, Takeda, Sawai, and Santen Pharmaceutical and grants from Eli Lilly, Pfizer and Tsumura outside the submitted work. C. Tassorelli reports, over the last 36 months, personal fees as a consultant or speaker from AbbVie, Dompè, Eli Lilly, Ipsen, Lundbeck, Pfizer, Organon and Teva, outside of the submitted work. She is PI in clinical trials sponsored by AbbVie, Eli Lilly, Ipsen, Lundbeck, Pfizer and Teva. CT also serves as an Associate Editor of Cephalalgia. M. Valeriani declares to be Associate Editor of The Journal of Headache and Pain and reports honoraria from Lusofarmaco, Teva, and Pfizer. He is Chief Editor of Pain Research and Management. D. Vuralli serves as member of Junior Editorial Board of The Journal of Headache and Pain. M. Waliszewska-Prosół declares to be Editorial Board Member of The Journal of Headache and Pain. S.J. Wang declares to be Associate Editor of The Journal of Headache and Pain. He has received honoraria as a moderator from AbbVie, Biogen, Eli-Lilly, Hava Biopharma, and Pfizer, has received consulting fees from AbbVie, Eli-Lilly Taiwan, Percept Co., and Pfizer Taiwan, and has been the PI in trials sponsored by Eli-Lilly, Lundbeck, and Novartis. He has received research grants from Taiwan branches of Eli Lilly, Novartis, and Orient Europharma. Y. Wang declares to be Associate Editor of The Journal of Headache and Pain. T. Wijeratne declares to be Associate Editor of The Journal of Headache and Pain. P. Martelletti M. declares to be Editor-in-Chief of The Journal of Headache and Pain.

Figures

**Fig. 1**
Posterior hypothalamic activation ipsilateral to the side of headache during an attack in comparison to the headache-free state as demonstrated through the use of a positron emission tomography scan. It is noteworthy that functional imaging studies have repeatedly demonstrated activation in the posterior hypothalamic gray matter at the level of the junction with the midbrain. This activation (of this part of the hypothalamus) is not observed in cases of migraine or other forms of experimental headache. The Journal of Headache and Pain needs to secure permission to reproduce the figure originally published in Neurology (10.1212/WNL.52.7.1522)

**Fig. 2**
Hypnogram overlaid with attack pattern and hypothetical implicated hormone fluctuations. Attacks might be related to sleep stage transitions during the night or daytime naps, or to relatively low melatonin and/or cortisol levels

**Fig. 3**
Timeline of the first evidence of efficacy for older drugs in the treatment of cluster headaches

**Fig. 4**
Factors involved in advocacy for cluster headache patients

See this image and copyright information in PMC

Comment on

Hallmarks of primary headache: part 2- Tension-type headache.
Pan LH, Ling YH, Wang SJ, Al-Hassany L, Chen WT, Chiang CC, Cho SJ, Chu MK, Coppola G, Pietra AD, Dong Z, Ekizoglu E, Els C, Farham F, Garcia-Azorin D, Ha WS, Hsiao FJ, Ishii R, Kim BK, Kissani N, Labastida-Ramirez A, Lange KS, Lytvyak E, Onan D, Ozge A, Papetti L, Pellesi L, Raffaelli B, Raggi A, Straube S, Takizawa T, Tanprawate S, Uludüz DU, Vongvaivanich K, Waliszewska-Prosół M, Wang Y, Wijeratne T, Wu JW, Yener SM, Martelletti P. Pan LH, et al. J Headache Pain. 2025 Jul 17;26(1):164. doi: 10.1186/s10194-025-02098-w. J Headache Pain. 2025. PMID: 40676501 Free PMC article. Review.

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Hallmarks of primary headache: part 3 - cluster headache

Affiliations

Hallmarks of primary headache: part 3 - cluster headache

Authors

Affiliations

Abstract

Conflict of interest statement

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