Hugo Gomez GARRIDO, Michele DILEONE, Jose Luis Martin CONTY, Begoña Polonio LOPEZ, Alfonso Martinez CANO, Juan Jose Bernal JIMENEZ, Fernando Castellanos PINEDO, Montserrat Zaragoza FERNÁNDEZ, Luis Domingo Daz SANCHEZ, Santiago San José PIZARRO, Ancor SANZ-GARCIA, Laura Mordillo MATEOS
Neurological Sciences and Neurophysiology - 2026;43(3):123-128
Background: Chronic migraine is a highly disabling neurologic disorder. Histamine is an inflammatory mediator and neurotransmitter that can activate meningeal afferents and interact with calcitonin gene-related peptide-dependent trigeminovascular signaling. In peripheral tissues, histamine is predominantly degraded by diamine oxidase (DAO). We hypothesized that higher serum DAO activity would be associated with fewer monthly migraine days (MMD) in chronic migraine. Methods: We prospectively screened 320 consecutive patients at a tertiary headache clinic; 80 met diagnostic criteria for chronic migraine, and 24 patients resistant to preventive therapy fulfilled inclusion criteria and were analyzed. Serum DAO activity was quantified using a validated radioextraction assay (DAO-REA(R)), and MMD as well as headache impact test (HIT-6) scores were averaged over the 3 months preceding blood sampling. Pearson's correlations were used to examine associations between DAO, MMD, and HIT-6. Results: Participants (19 women; mean age 43.5 +/- 10.2 years) reported a mean MMD of 21.1 +/- 4.4 days and HIT-6 of 65.3 +/- 4.9. Mean serum DAO activity was 17.3 +/- 7.8 U/mL, and no participant had low DAO activity by the assay's reference thresholds. DAO activity correlated inversely with MMD (r = -0.55; P = 0.005). DAO did not correlate with HIT-6, and MMD was not correlated with HIT-6 (P > 0.01). Conclusions: Higher serum DAO activity was associated with fewer MMDs in chronic migraine. These preliminary data support a potential modulatory role for DAO in migraine frequency and motivate larger, longitudinal studies incorporating histamine measurements and mechanistic endpoints. If validated, DAO activity could contribute to patient stratification and individualized management strategies.
