Serum tumor necrosis factor-α levels in migraine: a registry for migraine (REFORM) study

INTRODUCTION: Tumor necrosis factor alpha (TNF-α) has been implicated in neurobiologic mechanisms of migraine, yet its role across migraine subtypes remains insufficiently characterized.

OBJECTIVES: To compare serum TNF-α levels in adults with migraine, including specific subgroups, and healthy controls (HCs).

METHODS: In this cross-sectional, single-center study, adults diagnosed with migraine and sex-matched HCs were enrolled. Blood was drawn once from the antecubital vein, and serum TNF-α concentrations were measured using an ultrasensitive immunoassay. The primary outcome was the difference in TNF-α levels between all participants with migraine and HCs. Secondary outcomes included comparisons across migraine subgroups by aura (with vs without aura), chronicity (episodic vs chronic), and headache status at sampling (ictal vs interictal), as well as between each subgroup and HCs. Analysis of covariance models were adjusted for age, sex, body mass index, smoking, and other potential confounders.

RESULTS: In total, 633 participants with migraine and 154 sex-matched HCs provided eligible samples. No significant difference in serum TNF-α levels was observed between the overall migraine group and HCs (P = 0.052). However, subgroup analysis revealed that TNF-α levels in the migraine with aura group were 15.4% higher than in HCs (95% CI, 3.8%-28.2%; P = 0.004) and 10.6% higher than in the migraine without aura group (95% CI, 1.7%-20.3%; P = 0.012).

CONCLUSIONS: Elevated TNF-α levels in migraine with aura suggest an inflammatory component unique to this subtype. These findings support the hypothesis that migraine aura might be linked to a persistent, low-grade inflammatory process.