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Open research questions in Migraine and Headache Studies

685 gap statements mined from Migraine and Headache Studies papers in our 7.9M-paper local library, which holds 2,849 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

Choosing where to publish on Migraine and Headache Studies? See the ranked Medicine journals.

What the literature leaves open

  • The need to control for various factors that could affect cognition or somatosensory function, such as illiteracy, brain injury, diabetes, heavy alcohol use, stroke, spinal cord or peripheral neuropathy. The challenge of recruiting a sufficient number of participants with epilepsy, migraine, and their comorbidity, as well as healthy controls.

    Cognitive and sensory profiles in patients with epilepsy, migraine, and their comorbidity: a quantitative study · 2026 · DOI

  • Clinical evidence in migraine management using neurofeedback combined with mindfulness training remains limited. Methodological heterogeneity and small sample sizes have limited the generalizability of previous studies.

    Effect of neurofeedback-assisted mindfulness training on migraine severity, associated disability, sleep quality, and emotional distress: protocol for a randomized controlled trial · 2026 · DOI

  • Multidimensional evidence supports the existence of a bidirectional relationship between diet and migraine, but data are lacking on how this interplay actually impacts dietary intake and what it means for dietary recommendations.

    Needed Approaches for Dietary Research in Migraine · 2026 · DOI

  • The implications of long-term dietary intake on migraine prognosis are also not yet known due to lack of prospective data.

    Needed Approaches for Dietary Research in Migraine · 2026 · DOI

  • Although results are inconsistent across instruments, emerging data suggest that anti-CGRP mAbs and gepants, particularly erenumab, galcanezumab, and atogepant, can improve subjective sleep quality and objective measures such as sleep efficiency in some cases.

    Sleep and anti-calcitonin gene related peptide (CGRP) drugs: current evidence and perspectives · 2026 · DOI

  • Evidence for fremanezumab and eptinezumab remains scarce, whereas large-scale pharmacovigilance datasets indicate low rates of insomnia, somnolence, or abnormal dreams.

    Sleep and anti-calcitonin gene related peptide (CGRP) drugs: current evidence and perspectives · 2026 · DOI

  • However, this finding was based on few events and wide CIs and should be interpreted cautiously as limited evidence against a large relative increase in incident IS + TIA risk, rather than as definitive evidence of equivalent safety, absence of modest harm, or a protective effect.

    Cerebrovascular risk with calcitonin gene-related peptide monoclonal antibodies versus onabotulinumtoxinA in patients with migraine: A real-world pharmacoepidemiologic study in the National Institutes of Health All of Us Research Program · 2026 · DOI

  • Although migraine is a leading cause of disability worldwide and frequently results in emergency visits and productivity loss, it remains underrecognized in PCSC classifications.

    Migraine as a primary care-sensitive condition: Building pathways to accessible care · 2026 · DOI

  • AimIn view of limited evidence-based acute treatments for spontaneous vertigo in vestibular migraine, this real-world cohort study assessed the effectiveness of rimegepant for acute vestibular migraine-related vertigo and factors associated with treatment response.

    Effectiveness and clinical predictors of rimegepant for acute vertigo in vestibular migraine: A real-world cohort study · 2026 · DOI

  • BackgroundCandesartan and topiramate are both recommended for migraine prevention, but direct comparative data remain limited.

    Superior outcomes of candesartan over topiramate in the treatment of migraine: A comparative cohort study · 2026 · DOI

  • Whether this reflects a pharmacological advantage or a ceiling effect remains unclear.

    The chronopharmacology of atogepant in migraine prevention: A real-world evaluation of influence of timing of administration on effectiveness and tolerability · 2026 · DOI

  • BackgroundDespite consistent epidemiological evidence identifying smoking as a risk factor for medication-overuse headache (MOH), the mechanisms underlying this association remain incompletely elucidated.

    Smoking and medication-overuse headache: Exploring the potential link between nicotine dependence and analgesic overuse · 2026 · DOI

  • Despite their high prevalence and substantial functional impact, paediatric headache disorders remain under-recognised within health systems and under-represented in global policy frameworks.

    Migraine and headache in children and adolescents: A 2026 evidence-based factsheet · 2026 · DOI

  • Despite advances in neuroimaging, a sensitive and reliable morphological biomarker for episodic migraine (EM) remains elusive.

    Differentiating episodic migraine from healthy controls using fractal dimension analysis of MRI cortical morphology · 2026 · DOI

  • However, the link to the decline of estrogen in the post-ovulatory phase remains unclear.

    Migraine attack incidence in relation to the post-ovulatory estrogen decline: A prospective cohort study · 2026 · DOI

  • Supervised machine learning models trained on structured clinical data have shown good performance, whereas the diagnostic ability of large language models (LLMs) for headache disorders has not been evaluated.

    Comparative diagnostic agreement of a supervised machine learning model and a general-purpose, zero-shot, non-domain-adapted large language model for classifying headache disorders using structured questionnaires · 2026 · DOI

  • Aim The discrepancy in headache perception between people with and without headache disorders remains poorly studied.

    Perception of headache-related disability in individuals with and without headache disorders working in a municipal government in the Tokyo Metropolitan Area · 2026 · DOI

  • BackgroundPreventing migraine chronification is a key treatment goal, yet environmental and lifestyle contributors remain understudied in Asian populations.

    Environmental and psychological risk factors for migraine chronification in China: A multicenter prospective cohort study · 2026 · DOI

  • Glutathione (GSH) and glutamate (Glu) have been individually implicated in migraine pathophysiology, but their ratio as a marker of oxidative–excitatory balance in the thalamus—a key pain-processing hub—remains unexplored.

    Differential thalamic GSH/Glu ratios Among primary headache subtypes and clinical implications: A cross-sectional magnetic resonance spectroscopy study · 2026 · DOI

  • Further prospective controlled studies are warranted to validate these findings and to identify predictors of early functional response.

    Early and clinically meaningful functional improvement following CGRP monoclonal antibodies in adolescents with migraine: A real-world retrospective study · 2026 · DOI

  • Safety and tolerability findings are particularly notable given the limited evidence in this age group.

    Early and clinically meaningful functional improvement following CGRP monoclonal antibodies in adolescents with migraine: A real-world retrospective study · 2026 · DOI

  • BackgroundInsulin resistance (IR) may influence the treatment responses of medication-overuse headache (MOH), but evidence is limited.

    Association between insulin resistance surrogate indicators and six-month prognosis in patients with medication-overuse headache: A retrospective cohort study · 2026 · DOI

  • Few studies have examined which patients with migraine might be responders for mind-body interventions.

    Predictors of response to biofeedback-assisted relaxation for migraine: An exploratory analysis · 2026 · DOI

  • We review key MR findings across several domains of migraine research, noting areas of consistent evidence, as well as conflicting results.

    Mendelian randomization applied to migraine research: Opportunities and challenges · 2026 · DOI

  • Data-driven multimodal neuroimaging-based clustering in migraine identified two subgroups with distinct clinical and imaging patterns, highlighting heterogeneity and providing a framework for further investigation of imaging-informed characterization.

    Neuroimaging-based subtyping of migraine identifies clinically distinct phenotypes · 2026 · DOI

Most-cited papers in Migraine and Headache Studies

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Open questions raised by papers listed on this page include: (1) Clinical evidence in migraine management using neurofeedback combined with mindfulness training remains limited (“Effect of neurofeedback-assisted mindfulness training on migraine severity,…”, 2026); (2) Multidimensional evidence supports the existence of a bidirectional relationship between diet and migraine, but data are lacking on how this interplay actually impacts dietary intake and what it means for dietary recommendations (“Needed Approaches for Dietary Research in Migraine”, 2026); (3) Evidence for fremanezumab and eptinezumab remains scarce, whereas large-scale pharmacovigilance datasets indicate low rates of insomnia, somnolence, or abnormal dreams (“Sleep and anti-calcitonin gene related peptide (CGRP) drugs: current evidence…”, 2026); (4) BackgroundCandesartan and topiramate are both recommended for migraine prevention, but direct comparative data remain limited (“Superior outcomes of candesartan over topiramate in the treatment of migraine:…”, 2026); (5) Whether this reflects a pharmacological advantage or a ceiling effect remains unclear (“The chronopharmacology of atogepant in migraine prevention: A real-world…”, 2026). 685 gap statements have been mined from Migraine and Headache Studies papers in our 7.9M-paper local library, which holds 2,849 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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