Headache and Pain Research

Articles in E-pub version are posted online ahead of regular printed publication.

Review Article

Brain Glymphatic and Lymphatic Systems in Migraine: Mechanistic Insights and Neuromodulation Perspectives with an Emphasis on Ultrasound-Based Approaches: Jaeho Kim; Received January 12, 2026 Accepted January 30, 2026 Published online February 19, 2026; DOI: https://doi.org/10.62087/hpr.2026.0003 [Epub ahead of print]

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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.

Editorials

Pediatric Headache in Korea: Beyond a Common Complaint to a Chronic Neurological Condition: Yun Jin Lee; Received January 30, 2026 Accepted January 31, 2026 Published online February 13, 2026; DOI: https://doi.org/10.62087/hpr.2026.0006 [Epub ahead of print]

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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; Received January 6, 2026 Accepted January 26, 2026 Published online February 13, 2026; DOI: https://doi.org/10.62087/hpr.2026.0002 [Epub ahead of print]

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Original Articles

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; Received September 30, 2025 Accepted November 7, 2025 Published online February 13, 2026; DOI: https://doi.org/10.62087/hpr.2025.0021 [Epub ahead of print]

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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.

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; Received October 3, 2025 Accepted November 14, 2025 Published online January 28, 2026; DOI: https://doi.org/10.62087/hpr.2025.0022 [Epub ahead of print]

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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.

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