Original Research Articles
Vol. 36 No. 1 (2026)
https://doi.org/10.4081/cc.2026.15927

Investigating plasma neurofilament light chain levels in patients with migraine: a cross-sectional study

Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 9 July 2026
33
Views
21
Downloads
Migraine, neurofilament light chain, axonal injury, biomarkers, neurodegeneration

Authors

Elisa Maria Piella
Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Italy.
Silvia Boschi
silvia.boschi@unito.it
Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Italy.
Alessia Agostinelli
Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Italy.
Alberto Mario Chiarandon
Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Italy.
Fausto Roveta
Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Italy.
Chiara Costantino
Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Italy.
Giulia Gioiello
Clinical Biochemistry Laboratory “Baldi e Riberi”, AOU Città della Salute e della Scienza di Torino, Italy.
Giulia Montesano
Clinical Biochemistry Laboratory “Baldi e Riberi”, AOU Città della Salute e della Scienza di Torino, Italy.
Giulio Mengozzi
Clinical Biochemistry Laboratory “Baldi e Riberi”, AOU Città della Salute e della Scienza di Torino, Italy.
Innocenzo Rainero
Department of Neuroscience “Rita Levi Montalcini”, University of Turin; Headache Center, Department of Neuroscience and Mental Health, AOU Città della Salute e della Scienza di Torino, Italy.
Elisa Rubino
Department of Neuroscience “Rita Levi Montalcini”, University of Turin; Headache Center, Department of Neuroscience and Mental Health, AOU Città della Salute e della Scienza di Torino, Italy.

Background: Migraine is a complex neurovascular disorder that extends beyond recurrent pain attacks. Although migraine is primarily considered a disorder of neuronal dysfunction, accumulating neuroimaging and experimental evidence suggests subtle structural and molecular brain alterations. Neurofilament light chain (NfL) is a well-established biomarker of axonal injury and neurodegeneration, but its role in migraine remains unclear. The present study aimed to compare plasma NfL levels between adults with migraine and healthy controls, and to explore potential associations with clinical and demographic characteristics.

Methods: This study included patients with migraine fulfilling the International Classification of Headache Disorders (ICHD-3) criteria and a group of healthy subjects as controls. Plasma NfL concentrations were quantified using the fully automated Lumipulse® immunoassay platform (Fujirebio, Gent, Belgium). Associations between plasma NfL levels and demographic and clinical characteristics were analyzed using correlation analyses and regression models adjusted for relevant confounders.

Results: A total of 60 patients with migraine (42 with chronic migraine [CM], 70%) and 22 healthy controls were enrolled. Mean plasma NfL levels did not differ between migraine patients and controls (11.10±4.96 pg/mL vs. 11.20±6.00 pg/mL, respectively; p=0.935) or between episodic and CM subgroups. Moreover, no significant correlations were observed between NfL levels and age, monthly migraine days (MMD), migraine-related disability, pain intensity, aura, medication-overuse headache (MOH), or acute medication intake.

Conclusions: Migraine, including its chronic form, was not associated with detectable neuroaxonal damage based on circulating NfL levels, suggesting that neuroaxonal injury is not a prominent feature of the disease. Larger longitudinal studies are warranted to further clarify the role of neuroaxonal biomarkers in migraine pathophysiology.

Downloads

Download data is not yet available.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
1. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache 2001;41:646-57. DOI: https://doi.org/10.1046/j.1526-4610.2001.041007646.x
2. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38:1-211. DOI: https://doi.org/10.1177/0333102417738202
3. Katsarava Z, Buse DC, Manack AN, Lipton RB. Defining the differences between episodic migraine and chronic migraine. Curr Pain Headache Rep 2012;16:86-92. DOI: https://doi.org/10.1007/s11916-011-0233-z
4. Fang J, Wu J, Zhang T, Yuan X, Zhao J, Zheng L, et al. Serum neurofilament light chain levels in migraine patients: a monocentric case-control study in China. J Headache Pain 2023;24:149. DOI: https://doi.org/10.1186/s10194-023-01674-2
5. Süße M, Kloetzer C, Strauß S, Ruhnau J, Overeem LH, Bendig M, et al. Increased CX3CL1 in cerebrospinal fluid and ictal serum t-tau elevations in migraine: results from a cross-sectional exploratory case-control study. J Headache Pain 2024;25:46. DOI: https://doi.org/10.1186/s10194-024-01757-8
6. Xu WJ, Barisano G, Phung D, Chou B, Pinto SN, Lerner A, et al. Structural MRI in migraine: a review of migraine vascular and structural changes in brain parenchyma. J Cent Nerv Syst Dis 2023;15:11795735231167868. DOI: https://doi.org/10.1177/11795735231167868
7. Ashina S, Bentivegna E, Martelletti P, Eikermann-Haerter K. Structural and functional brain changes in migraine. Pain Ther 2021;10:211-23. DOI: https://doi.org/10.1007/s40122-021-00240-5
8. Chu C, Zhong R, Cai M, Li N, Lin W. Elevated blood S100B levels in patients with migraine: a systematic review and meta-analysis. Front Neurol 2022;13:914051. DOI: https://doi.org/10.3389/fneur.2022.914051
9. Gönen M, Özdoğan S, Balgetir F, Demir CF, Aytaç E, Müngen B, et al. S100B and neuron-specific enolase levels in episodic and chronic migraine. Acta Neurol Scand 2021;143:298-302. DOI: https://doi.org/10.1111/ane.13365
10. Overeem LH, Raffaelli B, Fleischmann R, Süße M, Vogelgesang A, Maceski AM, et al. Serum tau protein elevation in migraine: a cross-sectional case-control study. J Headache Pain 2023;24:130. DOI: https://doi.org/10.1186/s10194-023-01663-5
11. Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry 2019;90:870-81. DOI: https://doi.org/10.1136/jnnp-2018-320106
12. Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol 2018;14:577-89. DOI: https://doi.org/10.1038/s41582-018-0058-z
13. Gozalov E, Karlsson WK, Christensen RH, Al-Khazali HM, Hansen MB, Olsen DA et al. Serum GFAP and NfL levels in migraine: a registry for migraine (REFORM) study. Cephalalgia 2025;45:3331024251338178. DOI: https://doi.org/10.1177/03331024251338178
14. Colombo E, Doretti A, Rao R, Verde F, Sodano M, De Gobbi A, et al. Plasma levels of glial fibrillary acidic protein and neurofilament light chain in patients with chronic migraine: a multicenter case-control study. Neurol Sci 2025;46:2209-16. DOI: https://doi.org/10.1007/s10072-025-08011-2
15. Schwedt TJ, Chong CD, Wu T, Gaw N, Fu Y, Li J. Accurate classification of chronic migraine via brain magnetic resonance imaging. Headache 2015;55:762-77. DOI: https://doi.org/10.1111/head.12584
16. Rahimi R, Dolatshahi M, Abbasi-Feijani F, Momtazmanesh S, Momtazmanesh S, Aarabi MH, et al. Microstructural white matter alterations associated with migraine headaches: a systematic review of diffusion tensor imaging studies. Brain Imaging Behav. 2022;16:2375-2401. DOI: https://doi.org/10.1007/s11682-022-00690-1
17. Soheili-Nezhad S, Sedghi A, Schweser F, Babaki AES, Jahanshad N, Thompson PM, et al. Structural and functional reorganization of the brain in migraine without aura. Front Neurol 2019;10:442. DOI: https://doi.org/10.3389/fneur.2019.00442
18. Gross EC, Lisicki M, Fischer D, Sándor PS, Schoenen J. The metabolic face of migraine—from pathophysiology to treatment. Nat Rev Neurol 2019;15:627-43. DOI: https://doi.org/10.1038/s41582-019-0255-4

Supporting Agencies

This study was funded by grants from the Italian Ministry of the University (MUR), project “Dipartimenti di Eccellenza 2023-2027”, t o the Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Italy. ER reported a grant from Ricerca Locale, Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Italy.

How to Cite



1.
Investigating plasma neurofilament light chain levels in patients with migraine: a cross-sectional study. Confinia Cephalal [Internet]. 2026 Jul. 9 [cited 2026 Jul. 17];36(1). Available from: https://www.confiniacephalalgica.com/site/article/view/15927
Copyright (c) 2026 the Author(s) Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.