Calogero Calabrò^1,2 · Eliana Di Tillo¹ · Umberto Pensato^3,4 · Corrado Zenesini⁵ · Valentina Favoni⁵ · Camilla Fontana⁶ · Sabina Cevoli⁵ · Eliana Tossani⁷ · Pietro Cortelli^1,5 · Silvana Grandi⁷ · Giulia Pierangeli^1,5

Abstract

Objective The underpinning biologics of migraine chronification are not well understood. We aim to investigate the role of the cumulative burden of stress, namely the allostatic load, in migraine chronification.

Methods This was a cross-sectional study. The allostatic load was measured with a composite multi-system score (BALI: Bologna Allostatic Load Index), evaluating 20 biomarkers representing four physiological systems: immune, metabolic, cardiovascular, and neuroendocrinological systems. BALI score was subdivided into high score and low score based on the distribution in controls. Migraine patients were included and subclassified into low-frequency episodic migraine group (low- EM group), high-frequency episodic migraine group (high-EM group), and chronic migraine group (CM group).

Results The distribution of BALI high-score increased in parallel with headache attacks monthly frequency: 16% in low- EM group (n = 10), 24% in high-EM group (n = 12), and 40% in CM group (n = 21) (p = 0.017). In a multivariable analysis, the odds ratio of having a high-score BALI in CM patients (vs. low-EM patients) was 2.78 (95% CI 1.07–7.22; p = 0.036). Individual BALI biomarkers values which were significantly different among migraine subgroups included systolic blood pressure (p = 0.018), diastolic blood pressure (p < 0.001), and heart rate (p = 0.019).

Conclusion Our study substantiates this emerging concept of migraine chronification as an allostatic disorder.

Keywords Chronic migraine · Allostasis · Stress · Pathophysiology · Primary headache · Risk factor

GKB-NON-2024-00551