Headache and Pain Research

Editorial

Tension-Type Headache and Primary Stabbing Headache: Primary Headaches Beyond Migraine: Mi-Kyoung Kang; Received April 18, 2025 Accepted May 8, 2025 Published online June 5, 2025; DOI: https://doi.org/10.62087/hpr.2025.0007 [Epub ahead of print]

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Review Article

Genetic Architecture of Migraine: From Broad Insights to East Asian Perspectives: Joonho Kim, Min Kyung Chu; Received February 28, 2025 Accepted April 5, 2025 Published online May 27, 2025; DOI: https://doi.org/10.62087/hpr.2025.0003 [Epub ahead of print]

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Abstract PDF: Migraine is a complex neurological disorder with a strong genetic component, ranging from rare monogenic forms, such as familial hemiplegic migraine (FHM), to common polygenic migraine. FHM is primarily caused by mutations in CACNA1A, ATP1A2, and SCN1A, which affect ion channel function and cortical excitability. Additional genes, including PRRT2, have also been implicated, broadening the genetic landscape of monogenic migraine. Genome-wide association studies (GWAS) have identified multiple susceptibility loci for common migraine, highlighting key pathways related to neuronal excitability and vascular function. These findings have reinforced the neurovascular hypothesis of migraine pathogenesis. GWAS on other headache disorders, such as broadly defined headache or cluster headache, have also revealed both overlapping and distinct genetic risk factors. Genetic studies in East Asians have identified both ancestry-specific risk variants and overlapping loci with European populations, suggesting similarities in biological pathways while also highlighting population-specific differences in migraine susceptibility. Expanding research on the genetics of migraine in East Asian populations is essential for uncovering novel risk factors and improving the generalizability of genetic findings.

Original Article

Premonitory Symptoms in Migraine: Implications for Disease Burden and Cognitive Impairment, with Some Promising Answers: Utku Topbaş, Bahar Taşdelen, Nevra Öksüz Gürlen, Aynur Özge; Received November 29, 2024 Accepted January 10, 2025 Published online May 26, 2025; DOI: https://doi.org/10.62087/hpr.2024.0031 [Epub ahead of print]

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Abstract PDF: Purpose: This study evaluated the prevalence and impact of premonitory symptoms (PS) in people with migraine, assessing their influence on disability, cognitive function, and quality of life.
Methods
In a cross-sectional analysis at Mersin University Hospital, 186 migraine patients were interviewed to identify the presence of PS, using a structured questionnaire that included measures of disability (Migraine Disability Assessment Scale or MIDAS), quality of life (European Health Impact Scale or EUROHIS-8), and cognition (Migraine Attack Related Subjective Cognitive Scale or Mig-SCOG). Statistical analyses included descriptive statistics, the t-test, and the Mann-Whitney U-test, with a significance threshold set at p<0.05.
Results
Among participants, 74.7% reported one or more PS, with the most common being neck stiffness (64.7%), photophobia (56.8%), fatigue (52.8%), and phonophobia (50.3%). Patients with PS demonstrated significantly lower quality of life scores (EUROHIS-8, p<0.001) and higher cognitive impairment scores (Mig-SCOG, p<0.001) than those without PS, despite similar levels of migraine disability (MIDAS, p=0.050).
Conclusion
The high prevalence of PS in people with migraine and their association with greater cognitive impairment and reduced quality of life indicate that more targeted interventions are necessary in this subgroup. PS may be either a driver of cognitive and quality of life burden or just a marker of it, and disambiguating these possibilities will be a critical area for future research and clinical focus. More optimized and standardized prospective studies are needed to clarify the prevalence of PS.

Review Article

Efficacy and Safety of Repetitive Transcranial Magnetic Stimulation in Postherpetic Neuralgia: A Systematic Review and Meta-Analysis: Abdallah Abbas, Basant Lashin, Mohamed Abouzid, Hadir Mustafa Mohamed, Mohamed El-Moslemani, Mohamed A. Zanaty, Haneen Sabet, Dina Essam Abo-elnour, Ahmed Ibrahim Ghonimy Shedid, Mohamed Salah Mohamed Syed, Amna Hussein, Hoda Awad, Ahmed M. Raslan; Received December 6, 2024 Accepted January 10, 2025 Published online April 16, 2025; DOI: https://doi.org/10.62087/hpr.2024.0032 [Epub ahead of print]

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Abstract PDF Supplementary Material: This study evaluated the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) for pain management in postherpetic neuralgia (PHN). A comprehensive literature search was conducted through May 2024 in Scopus, PubMed, Web of Science, and Cochrane Library. Eligible studies included clinical trials, observational, and case-control studies. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using RoB 2 for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. Meta-analysis was performed using Review Manager v.5.3, with heterogeneity evaluated by chi-square and I² tests. Five studies (245 patients) were included, with rTMS sessions ranging from 10 to 28. Meta-analysis showed significant pain reduction with rTMS compared to sham treatment. At 2 weeks post-treatment, the mean pain score difference (visual analogue scale) was –1.44 (95% CI: –2.12 to –0.77; p<0.0001), with sustained relief at 1 and 3 months. However, no significant differences were found in the patient’s global impression of change scale, sleep quality, quality of life (QoL), medication regulation, or adverse events. rTMS exerted a consistent pain relief effect of rTMS, but its impact on broader aspects of patient well-being was less clear. rTMS provides sustained pain relief in PHN for up to 3 months, but its impact on QoL and secondary outcomes remains unclear, warranting further investigation.

Letter to the Editor

The honored list of reviewer in 2024: Headache Pain Res. 2025;26(1):88-88. Published online February 28, 2025; DOI: https://doi.org/10.62087/hpr.2025.0002

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Editorials

Exploring Secondary Headaches: Insights from Glaucoma and COVID-19 Infection: Soo-Kyoung Kim; Headache Pain Res. 2025;26(1):3-4. Published online February 24, 2025; DOI: https://doi.org/10.62087/hpr.2024.0033

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Beyond the Pain: Rethinking Migraine Care with the RELIEF PLAN Approach: Sanghyo Ryu; Headache Pain Res. 2025;26(1):1-2. Published online February 17, 2025; DOI: https://doi.org/10.62087/hpr.2024.0035

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Review Articles

Does Atogepant Offer a Safe and Efficacious Option for Episodic Migraine Prophylaxis? A Systematic Review and Meta-analysis: Ahmed Mostafa Amin, Abdallah Abbas, Samar Ahmed Amer, Hoda Awad, Mahmoud Tarek Hefnawy, Anas Mansour, Mohamed El-Moslemani, Haneen Sabet, Aynur Ozge; Headache Pain Res. 2025;26(1):21-37. Published online February 17, 2025; DOI: https://doi.org/10.62087/hpr.2024.0030

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Abstract PDF Supplementary Material: Migraine, a chronic neurological disorder, imposes a significant burden on individuals and healthcare systems globally. This systematic review and meta-analysis evaluated the efficacy and safety of atogepant in preventing episodic migraine (EM) in adults. A systematic search was conducted in four major databases (PubMed, Scopus, Web of Science, and Cochrane CENTRAL) up to June 2024. The inclusion criteria targeted randomized controlled trials (RCTs) comparing atogepant to placebo or standard care in patients with EM. Statistical analyses were performed using Review Manager (RevMan) software. Four RCTs with 2,018 patients receiving atogepant and 761 patients receiving placebo or standard care were included. Atogepant significantly reduced monthly migraine days compared to placebo at 10 mg daily (mean difference [MD], –1.16 days; 95% confidence interval [95% CI], –1.60 to –0.73), 30 mg daily (MD, –1.15 days; 95% CI, –1.64 to –0.66), 60 mg daily (MD, –1.48 days; 95% CI: –2.36 to –0.61 days), 30 mg twice daily (MD, –1.30 days; 95% CI, –2.17 to –0.43), and 60 mg twice daily (MD, –1.20 days; 95% CI, –1.90 to –0.50). A ≥50% reduction in migraine days was frequently significantly achieved with atogepant across all dosages. Atogepant was generally well tolerated, though it was associated with higher incidence rates of constipation and nausea compared to placebo. Atogepant is an effective and well-tolerated option for preventing EM, offering patients a noninvasive oral alternative to injectable therapies. Further research is warranted to explore its long-term safety and efficacy in diverse patient populations and refine its role in this field.

The Current Role of Artificial Intelligence in the Field of Headache Disorders, with a Focus on Migraine: A Systemic Review: Wonwoo Lee, Min Kyung Chu; Headache Pain Res. 2025;26(1):48-65. Published online February 17, 2025; DOI: https://doi.org/10.62087/hpr.2024.0024

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Abstract PDF: The application of artificial intelligence (AI) in the field of headache disorders, particularly migraine, is rapidly expanding, and AI has demonstrated significant potential for diagnosis, treatment, and research. This review examines the current role of AI in migraine management, categorizing AI applications into diagnosis and classification, assessment of treatment response, prediction of migraine attacks, and research. A systematic search of literature published between 2000 and 2024 was conducted, following PRISMA guidelines and utilizing the snowball technique. Of the 398 articles identified, along with five additional articles, 61 were finally reviewed. The results highlight promising AI applications, including the use of patient questionnaires, natural language processing, and imaging for migraine diagnosis, as well as predicting treatment responses and forecasting migraine attacks. Nonetheless, challenges remain in improving the accuracy, generalizability, validation, and clinical relevance of AI applications. Despite the substantial promise of AI for improving migraine management, it does not always guarantee better results than traditional methods. Careful consideration of the study design and method selection is crucial. Additionally, the interpretation of AI-generated results, particularly those from generative models, requires caution to avoid potential pitfalls.

Morning Headaches: An In-depth Review of Causes, Associated Disorders, and Management Strategies: Yooha Hong, Mi-Kyoung Kang, Min Seung Kim, Heejung Mo, Rebecca C. Cox, Hee-Jin Im; Headache Pain Res. 2025;26(1):66-79. Published online January 17, 2025; DOI: https://doi.org/10.62087/hpr.2024.0023

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Abstract PDF: Morning headaches, which are defined by occurrence upon or shortly after waking up in the morning, range from mild discomfort to severe pain and significantly impact an individual’s quality of life. Although morning headaches are a prevalent and potentially debilitating condition, the criteria for defining these headaches vary. The lack of universally accepted diagnostic criteria complicates understanding their etiology, associated factors, and potential interventions. The causes of morning headaches are multifaceted, including primary headache disorders like migraines and cluster headaches, and secondary causes such as sleep disorders, hypertension, abnormal intracranial pressure, and brain parenchymal diseases. Psychological factors, including anxiety and depression, as well as substance use, further complicate the clinical presentation, often requiring a multidisciplinary approach for effective diagnosis and treatment. This review provides a comprehensive overview of morning headaches, examining their various aspects and possible treatment options, with the goal of enhancing clinicians’ understanding and management of this common yet often overlooked condition.

Original Article

Evidence-Based Recommendations on Pharmacologic Treatment for Migraine Prevention: A Clinical Practice Guideline from the Korean Headache Society: Byung-Su Kim, Pil-Wook Chung, Jae Myun Chung, Kwang-Yeol Park, Heui-Soo Moon, Hong-Kyun Park, Dae-Woong Bae, Jong-Geun Seo, Jong-Hee Sohn, Tae-Jin Song, Seung-Han Lee, Kyungmi Oh, Mi Ji Lee, Myoung-Jin Cha, Yun-Ju Choi, Miyoung Choi; Headache Pain Res. 2025;26(1):5-20. Published online January 16, 2025; DOI: https://doi.org/10.62087/hpr.2024.0019

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2 Citations

Abstract PDF

Purpose: The aim of this clinical practice guideline (CPG) from the Korean Headache Society is to provide evidence-based recommendations on the pharmacologic treatment for migraine prevention in adult migraine patients.
Methods
The present CPG was developed based on the guideline adaptation methodology through a comprehensive systematic search for literature published between January 2012 and July 2020. The overall quality of the CPGs was assessed using the Korean version of the Appraisal of Guidelines for Research and Evaluation II tool. High-quality CPGs were adapted to make key recommendations in terms of strength (strong or weak) and direction (for or against).
Results
The authors selected nine available high-quality guidelines throughout the process of assessment of quality. Regarding oral migraine preventive medications, propranolol, metoprolol, flunarizine, sodium divalproex, and valproic acid are recommended to adult patients with episodic migraines based on high-quality evidence (“strong for”). Topiramate can be recommended for either episodic or chronic migraine (“strong for”). For migraine prevention using calcitonin gene-related peptide monoclonal antibodies, galcanezumab, fremanezumab, erenumab, and eptinezumab are recommended for adult patients with either episodic or chronic migraine on the basis of high-quality evidence (“strong for”). OnabotulinumtoxinA is recommended for adult patients with chronic migraine based on high-quality evidence (“strong for”). Last, frovatriptan, naratriptan, and zolmitriptan are recommended for short-term prevention in women with menstrual migraine (“strong for”).
Conclusion
In the present CPG, the authors provide specific, straightforward, and easy-to-implement evidence-based recommendations for pharmacologic migraine prevention. Nevertheless, these recommendations should be applied in real-world clinical practice based on optimal individualization.

Citations

Citations to this article as recorded by

One-Year Compliance After Calcitonin Gene-Related Peptide Monoclonal Antibody Therapy for Migraine Patients in a Real-World Setting: A Multicenter Cross-Sectional Study
Mi-kyoung Kang, Jong-Hee Sohn, Myoung-Jin Cha, Yoo Hwan Kim, Yooha Hong, Hee-Jin Im, Soo-Jin Cho
Journal of Clinical Medicine.2025; 14(3): 734. CrossRef
Beyond the Pain: Rethinking Migraine Care with the RELIEF PLAN Approach
Sanghyo Ryu
Headache and Pain Research.2025; 26(1): 1. CrossRef

Review Article

Update on Tension-type Headache: Hye Jeong Lee, Soo-Jin Cho, Jong-Geun Seo, Henrik Winther Schytz; Headache Pain Res. 2025;26(1):38-47. Published online December 30, 2024; DOI: https://doi.org/10.62087/hpr.2024.0025

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Abstract PDF: Tension-type headache (TTH) is the most common type of headache, characterized by mild to moderate intensity, bilateral, with a pressing or tightening (non-pulsating) quality. Migraine and TTH can occur in the same person, and their risk factors and treatments can overlap. However, TTH receives less attention than migraine. Furthermore, despite the expanding market for migraine treatments targeting calcitonin gene-related peptide (CGRP) mechanisms, the lack of evidence regarding mechanisms related to CGRP-related mechanisms in TTH continues to be neglected. There remains a need to develop effective preventive treatments for chronic TTH, which imposes a very high burden of disease. From this perspective, this review aims to provide the latest evidence on TTH.

Editorial

Nutritional Approaches to Managing Pediatric Migraine: Hye Eun Kwon; Headache Pain Res. 2024;25(2):75-76. Published online October 24, 2024; DOI: https://doi.org/10.62087/hpr.2024.0027

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Original Articles

Subjective Cognitive Decline Patterns in Patients with Migraine, with or without Depression, versus Non-depressed Older Adults: Sun Hwa Lee, Soo-Jin Cho; Headache Pain Res. 2024;25(2):103-110. Published online October 24, 2024; DOI: https://doi.org/10.62087/hpr.2024.0022

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Abstract PDF: Purpose: Cognitive decline is a common complaint in young patients with migraine, especially those with depression. Independent of psychiatric factors such as depression, subjective cognitive decline (SCD) is associated with an elevated risk of progression to dementia. This study aimed to investigate patterns of subjective cognitive complaints between migraineurs with or without depression and non-depressed older adults.
Methods
This retrospective study included 331 outpatients with SCD (293 from a headache clinic and 38 from a memory clinic). SCD was diagnosed as “yes” based on two questions about SCD. The Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess cognitive function. The SCD Questionnaire (SCD-Q) with three subdomains was analyzed to compare SCD between groups.
Results
Among patients with SCD, significant differences in duration of education were found among the groups—specifically, migraineurs with depression (12.39 years) had longer education than non-depressed older adults (10.50 years) and shorter education than migraineurs without depression (14.28 years). The total MMSE and MoCA scores did not differ between migraineurs with and without depression. Regarding SCD-Q scores, migraineurs with depression showed higher scores overall and in all cognitive domains than migraineurs without depression, with no significant difference compared to non-depressed older adults.
Conclusion
Although the depressed migraineurs with SCD were younger and more educated than the non-depressed older adults with SCD, both groups reported similarly high levels of SCD. Higher levels of surveillance for cognitive decline are warranted for migraineurs with depression who have SCD.

Bilateral Greater Occipital Nerve Block for Preventing the OnabotulinumtoxinA Wear-off Phenomenon in the Treatment of Chronic Migraine: A Case Series of 12 Patients: Sanghyun Kim, Jae Young An, Dae Woong Bae; Headache Pain Res. 2024;25(2):111-116. Published online October 23, 2024; DOI: https://doi.org/10.62087/hpr.2024.0021

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Abstract PDF

Purpose: OnabotulinumtoxinA is widely used to treat chronic migraines; however, the wear-off phenomenon before the next scheduled dose has emerged as a challenge. This study suggests a new strategy for preventing the wear-off phenomenon using bilateral greater occipital nerve block.
Methods
We conducted a retrospective review of patients diagnosed with chronic migraine who were treated with onabotulinumtoxinA and bilateral greater occipital nerve block at St. Vincent Hospital from January 2023 to December 2023. Twelve chronic migraine patients with a history of the wear-off phenomenon received a greater occipital nerve block 8 weeks after the initial onabotulinumtoxinA injection for two sessions. Responses to treatment were evaluated with regular follow-ups and daily headache diaries.
Results
All patients who had previously experienced the wear-off phenomenon with conventional onabotulinumtoxinA treatment did not experience the wear-off phenomenon during two sessions with an additional greater occipital nerve block administered 8 weeks after each onabolulinumtoxinA injection.
Conclusion
Bilateral greater occipital nerve block administered 8 weeks after the initial onabotulinumtoxinA injection effectively prevents the wear-off phenomenon, enabling sustained therapeutic benefits in chronic migraine patients. Further research is needed to confirm these findings in larger cohorts.

Citations

Citations to this article as recorded by

When Should Headache Specialists Hold a Needle? The Role of Botulinum Toxin Injections and Occipital Nerve Blocks
Soo-Jin Cho
Headache and Pain Research.2024; 25(2): 73. CrossRef

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