Headache and Pain Research

Volume 27(1); February 2026

Editorials

Primary or Secondary Headache Disorders in Moyamoya Disease and Cerebral Infarction: Clinical Challenges and the Potential Role of Non-Vasoconstrictive Migraine Therapies: Soo-Jin Cho; Headache Pain Res. 2026;27(1):1-3. Published online February 13, 2026; DOI: https://doi.org/10.62087/hpr.2026.0002

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Pediatric Headache in Korea: Beyond a Common Complaint to a Chronic Neurological Condition: Yun Jin Lee; Headache Pain Res. 2026;27(1):4-6. Published online February 13, 2026; DOI: https://doi.org/10.62087/hpr.2026.0006

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Review Articles

Headache and Stroke: A Review: Jong S. Kim; Headache Pain Res. 2026;27(1):7-12. Published online February 24, 2026; DOI: https://doi.org/10.62087/hpr.2025.0028

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Abstract PDF: Headache is a common disorder that is usually unaccompanied by focal neurological dysfunction. Less commonly, headache may be associated with central nervous system diseases such as stroke. Headache can occur at the time of stroke onset, but it may also precede or follow the onset of stroke. Nevertheless, headaches associated with stroke have not been sufficiently studied, in part because stroke physicians are primarily focused on diagnosis, risk factors, pathophysiological mechanisms, imaging findings, and treatment (e.g., thrombolysis and endovascular therapy) rather than on headache. In this narrative review, I describe the frequency and characteristics of headache across various stroke subtypes, including ischemic stroke, transient ischemic attack, intracerebral hemorrhage, subarachnoid hemorrhage, and other miscellaneous conditions such as venous infarction, arterial dissection, and reversible cerebral vasoconstriction syndrome.

Brain Glymphatic and Lymphatic Systems in Migraine: Mechanistic Insights and Neuromodulation Perspectives with an Emphasis on Ultrasound-Based Approaches: Jaeho Kim; Headache Pain Res. 2026;27(1):13-20. Published online February 19, 2026; DOI: https://doi.org/10.62087/hpr.2026.0003

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Abstract PDF: Migraine is a prevalent and disabling neurological disorder in which established pathophysiological mechanisms, including trigeminovascular activation and calcitonin gene-related peptide (CGRP) signaling, do not fully account for interindividual susceptibility, chronification, or treatment refractoriness. Advances in neurobiology have drawn attention to brain clearance pathways, specifically the glymphatic system and meningeal lymphatic vessels, as potential modulators of neuroinflammation and cerebrospinal fluid (CSF) dynamics. These systems regulate the exchange and drainage of CSF, interstitial solutes, and immune mediators and are strongly influenced by sleep and state-dependent physiology, both of which are closely linked to migraine pathophysiology. In this narrative review, we describe the anatomical and functional organization of brain lymphatic and glymphatic systems and critically evaluate emerging evidence connecting these pathways to migraine. Indirect human imaging studies and experimental models indicate that alterations in perivascular transport, meningeal lymphatic drainage, sleep disruption, and CGRP-related signaling may converge to modulate brain clearance efficiency in migraine. Although the available evidence remains heterogeneous and largely indirect, these findings offer a coherent framework for integrating clearance-related physiology into existing migraine models. We further discuss neuromodulation as a potential strategy for influencing brain clearance mechanisms. In particular, transcranial low-intensity ultrasound has been shown to enhance CSF movement in vivo, providing direct mechanistic support for clearance modulation. Other neuromodulation modalities may exert indirect effects through autonomic regulation, neural oscillations, or vascular dynamics. While clinical evidence remains preliminary, a clearance-oriented perspective may help guide future biomarker development and translational research in migraine.

Alcohol-Induced Headache: A Narrative Review Based on Migraine Pathophysiology: Woo-Seok Ha; Headache Pain Res. 2026;27(1):21-29. Published online February 23, 2026; DOI: https://doi.org/10.62087/hpr.2025.0027

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Abstract PDF: Alcohol-induced headache (AIH) is one of the most common headache experiences and is associated with a substantial socioeconomic burden; however, its pathophysiological mechanisms and clinical classification remain inadequately defined. Accumulating evidence indicates that AIH shares key biological pathways with migraine, particularly involving activation of the trigeminovascular system and calcitonin gene-related peptide (CGRP) signaling. Although currently available hangover remedies are supported by limited high-quality evidence, anti-CGRP treatments have emerged as a biologically plausible option for the situational prevention and acute treatment of AIH. A phenotype-based approach is therefore essential for achieving accurate diagnosis and effective management of alcohol-related headaches. Future well-designed clinical trials focusing on CGRP antagonists are warranted to address this common yet neglected disorder.

Original Articles

Natural Diagnostic Classes of Headache Disorders: Latent Class Analysis of a Population-Based Study: Wonwoo Lee, Seok-Jae Heo, Jungyon Yum, Min Kyung Chu; Headache Pain Res. 2026;27(1):30-42. Published online February 26, 2026; DOI: https://doi.org/10.62087/hpr.2026.0004

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Abstract PDF Supplementary Material: Purpose: The International Classification of Headache Disorders, 3rd edition (ICHD-3), defines headache diagnoses based on combinations of clinical symptoms. Diagnostic overlap is common, and symptom variability complicates diagnostic classification. We evaluated natural classes of headache disorders using a statistical approach and compared these classes with ICHD-3 diagnostic categories.
Methods
Data from a nationwide, population-based web survey on headache and sleep conducted in South Korea (n=3,030) were analyzed. Participants who reported headache within the past year (n=1,938) were included. Latent class analysis was performed using categorical ICHD-3 diagnostic criteria to identify distinct classes. The characteristics of each class and the distribution of ICHD-3 primary headache diagnoses were examined.
Results
Nine classes were identified, comprising 626, 54, 248, 148, 187, 143, 79, 61, and 392 individuals. Three classes were tension-type headache (TTH)–like: Class 1 was male-dominant mild bilateral TTH, Class 8 represented classic, severe TTH, and Class 9 was mild unilateral TTH. Class 4 showed a typical migraine phenotype and contained most migraine cases. Classes 5 and 6 were dominated by probable migraine (PM) and differed mainly in sensory sensitivity and disability, which were higher in Class 6. Classes 2, 3, and 7 were categorized as “other headache.” Class 2 had the highest prevalence of medication-overuse headache (MOH), whereas Class 3 was characterized by mild headache with nausea. Class 7 showed a mixed-type profile with prominent photophobia. Severity and central sensitization markers were key classifiers.
Conclusion
Latent class analysis identified nine clinically distinct headache classes. PM was clearly distinct from both TTH and migraine. One subtype within the “other headache” class showed the highest MOH burden.

The Impact of Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies on Sleep Quality and Daytime Sleepiness in Migraine Patients: A Multicenter Study: Rita Cagigal, Ângelo Fonseca, Bárbara Martins, Catarina Fernandes, Sandra Palma, Carolina Guerreiro, Carla Morgado, Diana Valente, Miguel Miranda, Joana Silva, Miguel Saianda-Duarte, Sofia Casanova, Mariana Branco, Ana Luísa Rocha, Henrique Delgado, Elsa Parreira, Filipe Palavra; Headache Pain Res. 2026;27(1):43-51. Published online January 28, 2026; DOI: https://doi.org/10.62087/hpr.2025.0022

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Abstract PDF: Purpose: This study aimed to determine whether patients with migraine experience improvements in self-reported sleep quality and daytime sleepiness after starting monoclonal antibody (mAb) therapy targeting the calcitonin gene-related peptide (CGRP) or its receptor, and to explore the association between treatment efficacy and improvements in sleep quality.
Methods
This prospective, multicenter, observational, longitudinal study was conducted across 12 headache centers. Adults with episodic or chronic migraine who began anti-CGRP mAb therapy were assessed at baseline, 3 months, and 6 months. Sleep quality and daytime sleepiness were evaluated using the Portuguese version of the Pittsburgh Sleep Quality Index (PSQI-PT) and the Portuguese version of the Epworth Sleepiness Scale (ESS-PT), respectively.
Results
Of 118 enrolled patients, 109 completed the study (86.4% female; mean age, 43.6 years). A significant improvement in sleep quality was observed, with median PSQI-PT scores decreasing from 9 at baseline to 6 at 6 months (p<0.001). Daytime sleepiness also improved, with median ESS-PT scores decreasing from 7 to 6 (p=0.04). Migraine frequency decreased significantly, from a median of 13 to 4 monthly migraine days (p<0.001). Greater migraine improvement was independently associated with greater PSQI-PT improvement (p<0.001), whereas changes in ESS-PT were not correlated with treatment efficacy.
Conclusion
Anti-CGRP mAb therapy was associated with significant improvements in sleep quality, likely mediated through migraine relief. Changes in ESS-PT were not correlated with treatment efficacy, suggesting a possible interaction between migraine mechanisms and CGRP-mediated sleep–wake regulation. Future research should focus on clarifying the mechanisms underlying these associations.

Cerebrovascular Hemodynamic Responses to Breath-Holding in Migraine: A Longitudinal Functional Near-Infrared Spectroscopy Study Comparing a Calcitonin Gene-Related Peptide Monoclonal Antibody and Oral Preventive Treatment: Dong A. Yea, Jong Kwan Choi, Yoo Hwan Kim; Headache Pain Res. 2026;27(1):52-63. Published online February 24, 2026; DOI: https://doi.org/10.62087/hpr.2025.0029

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Abstract PDF Supplementary Material: Purpose: Altered cerebrovascular reactivity has been reported in migraine; however, longitudinal changes during preventive treatment remain unclear. This observational study aimed to describe and compare longitudinal cerebrovascular responses derived from functional near-infrared spectroscopy (fNIRS) during a breath-holding test between patients treated with a calcitonin gene-related peptide (CGRP) monoclonal antibody and those receiving oral preventive medications.
Methods
Twenty-four patients with migraine were enrolled (CGRP group, n=12; oral group, n=12). fNIRS over the prefrontal cortex was performed at baseline and after 3 months during a standardized breath-holding protocol. Oxygenated (HbO), deoxygenated, and total hemoglobin signals were used to derive breath-holding and recovery indices. Clinical outcomes included monthly headache days, acute medication days, disability, mood scales, and Patient Global Impression of Change.
Results
Monthly headache days decreased in both groups (CGRP: Δ=–2.00, p=0.26; oral: Δ=–1.50, p=0.48), with no between- group difference (p=0.85). Acute medication days were significantly reduced only in the CGRP group (Δ=–7.00, p=0.03). Migraine Disability Assessment (MIDAS) scores improved significantly in the CGRP group (Δ=–21.25, p=0.02), with no significant between-group differences. During breath-holding, HbO increased across channels in both groups and was followed by a gradual decline during the recovery phase. Longitudinal analyses demonstrated group-dependent differences in temporal change patterns, with a treatment×time interaction reaching significance at the uncorrected level in a representative channel (Channel 6: F(1,16)=8.448, p=0.010), but not after multiple-comparison correction (p=0.155).
Conclusion
fNIRS with a breath-holding challenge enables longitudinal assessment of cerebrovascular responses during migraine preventive treatment. The observed differences should be interpreted descriptively in terms of temporal change patterns. Larger studies are needed to clarify clinical significance.

Adult-Onset versus Pediatric-Onset Episodic Cluster Headaches: Results from the Korean Cluster Headache Registry: Pil-Wook Chung, Byung-Su Kim, Jeong-Wook Park, Jong-Hee Sohn, Mi Ji Lee, Byung-Kun Kim, Min Kyung Chu, Tae-Jin Song, Soo-Kyoung Kim, Heui-Soo Moon, Kyungmi Oh, Soo-Jin Cho; Headache Pain Res. 2026;27(1):64-70. Published online February 13, 2026; DOI: https://doi.org/10.62087/hpr.2025.0021

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Abstract PDF: Purpose: This study aimed to compare clinical characteristics between pediatric-onset and adult-onset cluster headache (CH) using data from the Korean Cluster Headache Registry, a nationwide, prospective, multicenter registry.
Methods
This cross-sectional observational study analyzed data collected over a 4-year period from a prospective multicenter registry. A total of 337 patients aged ≥19 years with episodic CH were included. Participants were classified as having pediatric-onset CH (onset≤18 years) or adult-onset CH (onset>18 years). Demographic and clinical features, smoking status, and psychiatric comorbidities were compared between groups.
Results
Pediatric-onset CH was reported in 24.6% of patients (n=83). The diagnostic delay was significantly longer in the pediatric-onset group compared with the adult-onset group (10.1 years vs. 6.2 years, p<0.001). Patients with pediatric-onset CH experienced more severe headache attacks (numerical rating scale 9.2 vs. 8.9, p=0.025), although attack duration, frequency, and other clinical features were similar between groups. Smoking exposure was lower in the pediatric-onset group, suggesting potential differences in environmental risk factors. No significant differences were observed in psychiatric comorbidity or headache-related disability.
Conclusion
Pediatric-onset CH is relatively common and shares most clinical features with adult-onset CH, apart from greater attack severity and lower smoking exposure. The longer diagnostic delay in pediatric-onset cases highlights the need for improved awareness and earlier recognition. Further research is warranted to elucidate the underlying pathophysiological mechanisms and long-term outcomes in pediatric-onset CH.

Letter to the Editor

The honored list of reviewer in 2025: Headache Pain Res. 2026;27(1):71-71. Published online February 26, 2026; DOI: https://doi.org/10.62087/hpr.2026.0001

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