The hallmarks of migraine: a paper and a wager
Published in General & Internal Medicine
This was not the first time in which I coordinated a large effort on the Journal of Headache and Pain. Surely, this was the time in which I enjoyed more ... as the story begins and ends with a wager.
The wager was to coordinate a complex task, in which the idea was to bring together a set of recognized experts in their respective fields, together with some "future experts", to get to a simple point: creating a "masterpiece" for migraine-related science. But also, creating a ground for a cultural position on the way in which migraine is approached. But also, combining different expertise and experiences, mixing that of recognized scientists and clinicians with that of people who are promising in their fields, the so called future experts. And, in the middle of this, we had to put together all of the knowledgeable about migraine. This could be quite complex, and boring: so, we turned it into a funny activity. And we did it.
Synthesizing a 47-page long paper is almost impossible, but here I wish to provide some ideas on the worth of this work. We decided that the idea behind the term "hallmarks" should not be strict, i.e. the most typical and distinctive sign and symptoms, but large: and we included issues related to personal impact, economic evaluation, workplace impact, pharmacovigilance...so not only a strict scientific and clinical paper, but a cultural one. Although simple, our conclusion on the most relevant hallmark of migraine, was that migraine has common and individual features together. The common ones basically include migraine clinical manifestations, i.e. unilateral location of headache, with pulsating quality, pain of moderate/severe intensity, which is aggravated by physical activity and associated to either nausea, photophobia or phonophobia. Apart from this, migraine is a land of heterogeneity, which likely reflects genetics and molecular bases, as well as the different exposure to environmental factors. All of this determines a variable response to treatments and the need to manage migraine with a multi-modal approach.
However, medical research on headaches particularly suffers from the syndrome of single-disease niche sub-specialties, determining a poor propensity for comparison among different disciplines and areas of intervention, including medical, behavioral and related to prevention in a public health perspective. The output of this monolithic approach is that research results might be brilliant, but yet lack a systematic project articulation. This is evident in the little to no interpretative vision of research findings, resulting in a reduced attractiveness of funding.
This is precisely the cultural value of the hallmarks of migraine paper: presenting an updated view on migraine knowledge with a paramount vision on the persons who suffer from it. Researchers and clinicians with an interest on migraine must have a cross-sectional and joint vision with other niche disease specialties and must stop relegating themselves to the role of fine technicians in the service of an organ or a function.
Presenting this view on migraine was our wager. We did it and we enjoyed while doing it: so enjoy reading as we enjoyed writing.
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The Journal of Headache and Pain
The Journal of Headache and Pain is a peer-reviewed open access journal specifically dedicated to researchers involved in all aspects of headache and related pain syndromes, including epidemiology, public health, basic science, translational medicine, clinical trials and real-world data.
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Focus Africa
The Journal of Headache and Pain is calling for submissions to our Collection on Focus Africa. Migraine is a major cause of disability worldwide, yet research efforts and healthcare strategies remain unevenly distributed across regions. In Africa, diverse populations and healthcare landscapes present unique challenges in the recognition, diagnosis, and management of migraine and other headache disorders. This thematic collection, Focus Africa, aims to enhance understanding of these conditions by exploring epidemiological trends, healthcare disparities, cultural influences, financial constraints, gender-related factors, and the availability of treatment options across the continent.
We invite submissions of original research, systematic and narrative reviews, editorials, rapid reviews, and commentaries on topics including, but not limited to:
• The prevalence, burden, and impact of migraine and other headache disorders across African countries
• Socio-economic and cultural determinants of headache disorders in Africa
• Insights into the pathophysiology of migraine from an African perspective
• Barriers to headache care, healthcare inequalities, and policy solutions
This Collection provides a dedicated platform for African researchers and clinicians to contribute to global headache science while addressing the specific needs of the region. By fostering collaboration and knowledge exchange, Focus Africa aims to drive meaningful advancements in migraine and headache disorders research and care across the continent.
Therefore, the collection welcomes researchers from author groups all with their main affiliated institution in Africa. Cross-continental authorship groups are welcome to submit their work to The Journal of Headache and Pain outside of this collection.
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Publishing Model: Open Access
Deadline: Dec 20, 2025
The Epigenome and Transcriptome in Headache Disorders
The thematic series titled "The Epigenome and Transcriptome in Headache Disorders" focuses on the latest advancements in the studies on the epigenome and transcriptome in headache research, aiming to elucidate the complex neurological mechanisms underlying headache disorders, particularly migraine and tension-type headaches. This collection explores how the regulation of gene expression with a special emphasis on its epigenetic and transcriptomics components with corresponding techniques are being applied to analyze clinical, neurophysiological, and molecular data, uncovering patterns and subtle relationships within the intricate landscape of headache-related phenomena.
The studies of the epigenome and transcriptome offer new perspectives for understanding the complex interplay between genetic predispositions, environmental triggers, and individualized symptomatology. This collection delves into how epigenetic modifications influence the onset, frequency, and individual variability of headaches, providing insights that support the development of personalized treatment strategies and advancing the field of precision medicine.
Additionally, the collection highlights the potential of the epigenome and transcriptome in enhancing early diagnosis, predicting headache occurrences, and optimizing treatment approaches. Through innovative molecular biology techniques, the collection aims to offer a deeper understanding of headache disorders and pave the way for more effective therapeutic interventions.
The collection also invites discussion on the ethical implications of diagnostic and therapeutic approaches based on epigenetic and transcriptome findings. Our goal is to improve the quality of headache diagnosis and treatment in an effective and ethically responsible manner.
This Collection supports and amplifies research related to SDG 3, Good Health and Well-Being.
All submissions in this collection undergo the journal’s standard peer review process. Similarly, all manuscripts authored by a Guest Editor(s) will be handled by the Editor-in-Chief. As an open access publication, this journal levies an article processing fee (details here). We recognize that many key stakeholders may not have access to such resources and are committed to supporting participation in this issue wherever resources are a barrier. For more information about what support may be available, please visit OA funding and support, or email OAfundingpolicy@springernature.com or the Editor-in-Chief.
Publishing Model: Open Access
Deadline: Feb 28, 2026
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A seminal paper to be scattered everywhere in a still jeopardized scientific area. Great leadership of Alberto Raggi in coordinating 40 global authors.
Thank you prof. Martelletti: a great opportunity for me and for a fantastic group of authors!
Excellent work!