Migraine is a prevalent neurological disorder, yet its pathophysiology remains incompletely understood. While the role of neuroinflammation and metabolic dysregulation in migraine pathogenesis is increasingly recognized, the kynurenine pathway has gained attention due to its involvement in tryptophan metabolism. Our study aims to evaluate the relationship between kynurenine metabolism, the clinical characteristics of migraine, and the process of migraine chronification.

This study was designed as a prospective, observational study and was conducted with a total of 81 participants including 27 with episodic migraines, 27 with chronic migraines, and 27 healthy controls, aged 18–50 years. Data collected included age, sex, pain type and location of migraine, attack frequency, severity, disease duration, and body mass index. Blood samples taken during the interictal phase were analyzed for Tryptophan (TRP), L-kynurenine (KYN), 3-hydroxykynurenine (3-HK), and 3-hydroxyanthranilic acid dioxygenase (3-HAAO) levels using ELISA kits.

In the comparison between healthy controls and migraine groups, age, sex, and body mass index were similar. However, the patient group exhibited significantly lower levels of Trp, KYN, 3-HK, and 3-HAAO compared to the control group ( P < 0.001 for each). Laboratory analysis revealed higher levels of HAAO, 3-HK, KYN, and Trp in the episodic migraine group than in the chronic migraine group ( P p = 0.027, P < 0.001, P < 0.001, P = 0.002, respectively). ROC analysis revealed that 3-HK was identified as an independent risk factor for CM (OR = 0.403, P < 0.001). Painful headache days, monthly attack frequency, MIDAS, and HIT-6 scores were negatively correlated with HAAO, 3-HK, KYN, and Trp levels ( P < 0.005 for each).

The study suggests that all four molecules are potentially involved in migraine clinical features and its chronification. Their levels decrease as migraine attacks worsen due to their neuroprotective effects. Future studies should explore targeted therapies to modulate kynurenine metabolism to prevent chronic migraine.