Conference Coverage

Cross-Sectional Study Links Higher Serum Autotaxin Levels With Episodic, Chronic Migraine

Edited by:
Anthony Calabro, MA

Key Highlights

  • Serum autotaxin levels were significantly higher in patients with episodic migraine and chronic migraine compared with healthy controls.
  • In chronic migraine, elevated autotaxin levels were associated with migraine intensity, headache frequency, and evolution time.
  • Autotaxin correlated with biomarkers related to trigeminovascular system activation, endothelial dysfunction, and inflammation.
  • The researchers concluded that further studies are needed to clarify the potential role of autotaxin as a therapeutic target for migraine.

Serum autotaxin (ATX) levels were significantly increased in patients with episodic migraine and chronic migraine compared with healthy controls, according to the results of the 2026 Basic Science Award-winning study, “Serum Levels of Autotaxin Reveal Its Role as a Novel Biomarker of Migraine.”

Alberto Ouro, PhD, of the Health Research Institute of Santiago de Compostela in Galicia, Spain, received the award, which is given to the top basic science article published in Headache during the previous year, and presented its findings at the American Headache Society 68th Annual Scientific Meeting in Orlando, FL.

The researchers evaluated ATX because it is a plasma enzyme that promotes lysophosphatidic acid formation, a lipid involved in biological functions relevant to migraine, including vascular tone control, inflammation, neuronal excitation, endothelial dysfunction, and neuropathic pain. They also noted that ATX is physiologically higher in the serum of females compared with males, and most patients with migraine are female.

The cross-sectional study included healthy controls (n = 62), patients with episodic migraine (n = 45), and patients with chronic migraine (n = 38). Investigators assessed clinical outcomes, including migraine intensity (visual analog scale), headache frequency (days per month), evolution time (months), and attack duration (hours). They also evaluated serum biomarkers of inflammation, trigeminovascular system activation, endothelial dysfunction, and ATX, as well as serum lipidomic biomarker profiles.

Study Findings

Mean serum ATX levels were significantly elevated in patients with episodic migraine (310.7 [79.7] ng/mL) and chronic migraine (336.7 [66.9] ng/mL) compared with healthy controls (212.3 [53.2] ng/mL; P < .001). In patients with chronic migraine, higher ATX levels were associated with migraine intensity, as measured by visual analog scale score (Spearman coefficient = 0.405; P < .05), headache frequency (Spearman coefficient = 0.718; P < .001), and evolution time (Spearman coefficient = 0.2257; P < .01).

ATX also correlated with multiple serum biomarkers described in migraine. These included calcitonin gene-related peptide (CGRP) (Pearson coefficient = 0.278; P < .001), pentraxin 3 (Pearson coefficient = 0.468; P < .001), soluble tumor necrosis factor-like weak inducer of apoptosis (Pearson coefficient = 0.242; P < .001), cellular fibrinogen (Pearson coefficient = 0.252; P < .01), and interleukin 6 (Pearson coefficient = 0.159; P < .001). The researchers also reported that a marked decrease in serum lysophosphatidylcholine levels indicated high ATX activity in patients with migraine. These findings are from the study only and should not be extrapolated beyond the reported cohort.

Clinical Implications

According to the study authors, the findings suggest that serum ATX may serve as a novel biomarker for migraine. They reported that ATX was increased in both episodic and chronic migraine and correlated with clinical outcomes as well as biomarkers related to CGRP, endothelial dysfunction, and inflammation.

The authors stated that further studies are necessary to elucidate the potential role of ATX as a therapeutic target for migraine.

Expert Commentary

“Serum levels of ATX were significantly increased in patients with EM and CM. In addition, ATX correlates with clinical outcomes, as well as CGRP, endothelial dysfunction and inflammation biomarkers. Further studies are necessary to elucidate the potential role of ATX as a therapeutic target for migraine,” the researchers concluded.

Reference
Ouro A, Castro-Mosquera M, Rodríguez-Arrizabalaga M, Debasa-Mouce M, Romaus-Sanjurjo D, Aramburu-Nuñez M, et al. Serum levels of autotaxin reveal its role as a novel biomarker of migraine. Headache. Published online 2025. doi:10.1111/head.14922. PMID:40035380.