Evidence map›Paper›PMID 41039211›Full record

ReviewThe journal of headache and pain2025

Hallmarks of primary headache: part 3 - cluster headache.

Gianluca Coppola, Marco Antônio Arruda, Messoud Ashina, Mads Barloese, Andrea Carmine Belin, Sara Bottiroli, Debashish Chowdhury, Roberto De Icco, Cherubino Di Lorenzo, Giulia Di Stefano and 38 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The journal of headache and pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. Review
  7. Observational
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

48 authors.

Gianluca CoppolaDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Via Franco Faggiana, Latina, 1668 - 04100, Italy. gianluca.coppola@uniroma1.it.
Marco Antônio ArrudaGlia Institute, Ribeirão Preto, SP, Brazil.
Messoud AshinaDepartment of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Mads BarloeseDepartment of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Andrea Carmine BelinCentre for Cluster Headache, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Sara BottiroliDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Debashish ChowdhuryGB Pant Institute of Postgraduate Medical Education and Research, New Delhi, India.
Roberto De IccoDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Cherubino Di LorenzoDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Via Franco Faggiana, Latina, 1668 - 04100, Italy.
Giulia Di StefanoDepartment of Human Neuroscience, Sapienza University of Rome, Rome, Italy.
Jacob C A EdvinssonDepartment of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.
Stefan EversFaculty of Medicine, University of Münster, Münster, Germany.
Stefania FerraroMinistry of Education Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology, Chengdu, China.
Rolf FronczekDepartment of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
David García-AzorínDepartment of Neurology, Hospital Universitario del Rio Hortega, Valladolid, Spain.
Peter J GoadsbyNIHR King's Clinical Research Facility, King's College, London, UK.
Licia GrazziHeadache Center, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Dagny HolleDepartment of Neurology, West German Headache and Vertigo Center, Essen University Hospital (AöR), Essen, Germany.
Julia J JansenDepartment of Neurology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands.
Raquel Gil-GouveiaNeurology Department, Hospital da Luz Lisboa, Lisboa, Portugal.
Giorgio LambruHeadache and Facial Pain Service, Guy's and St Thomas' Hospital, London, UK.
Michel Lanteri-MinetDépartement Douleur, FHU InovPain, UR2CA, Centre Hospitalier Universitaire de Nice - Université Côte Azur, Nice, France.
Marco LisickiHeadache Research Laboratory, Mercedes & Martín Ferreyra Institute, National Scientific and Technical Research Council (CONICET), National University of Córdoba, Cordoba, Argentina.
Dimos D MitsikostasNeurology Department, Aeginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Teshamae MonteithDepartment of Neurology - Headache Division, Miller School of Medicine, University of Miami, Miami, FL, USA.
Danilo Antonio MontisanoHeadache Center, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Mark ObermannDepartment of Neurology, Klinikum Weser-Egge, Höxter, Germany.
Li-Ling Hope PanBrain Research Center, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Kuan-Po PengDepartment of Systems Neuroscience, University Medical Center- Hamburg Eppendorf, Hamburg, Germany.
Mario PeresHospital Israelita Albert Einstein, , Instituto de Psiquiatria, HCFMUSP, Sao Paulo, Brazil.
Igor PetrušićLaboratory for Advanced Analysis of Neuroimages, Faculty of Physical Chemistry, University of Belgrade, Belgrade, Serbia.
Alberto Proietti CecchiniHeadache Center, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Marta Vila-PueyoHeadache and Neurological Pain Research Group, Vall d'Hebron Research Institute (VHIR), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Alberto Raggi41. Neurology, Public Health and Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Innocenzo RaineroHeadache Center, Department of Neuroscience "Rita Levi Montalcini", University of Torino, Turin, Italy.
Giorgio SandriniDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Gabriele SebastianelliDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, Via Franco Faggiana, Latina, 1668 - 04100, Italy.
Tsubasa TakizawaDepartment of Neurology, Keio University School of Medicine, Tokyo, Japan.
Surat TanprawateThe Northern Neuroscience Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Cristina TassorelliDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Andrea TruiniDepartment of Human Neuroscience, Sapienza University of Rome, Rome, Italy.
Massimiliano ValerianiDevelopmental Neurology Unit, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Doga VuralliDepartment of Neurology and Algology, Neuroscience and Neurotechnology Center of Excellence (NÖROM), Neuropsychiatry Center, Gazi University Faculty of Medicine, Ankara, Turkey.
Marta Waliszewska-ProsółDepartment of Neurology, Wroclaw Medical University, Wroclaw, Poland.
Shuu-Jiun WangBrain Research Center, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Yonggang WangDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Tissa WijeratneDepartment of Neurology, Department of Medicine, Melbourne Medical School, Sunshine Hospital, Western Health, St Albans, Australia.
Paolo MartellettiSchool of Health, Unitelma Sapienza University of Rome, Rome, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCluster 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

findingsDespite 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.

conclusionsCH 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.

Indexed as

Cluster HeadacheHumansAdvocacyCircadian rhythmHypothalamusNeuromodulationNeuropeptidesPrimary headachePsychological factorsTreatmentsTrigeminal-autonomic system

Identifiers

PMID41039211
PMCPMC12490097

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.