[New perspectives in the treatment of migraine: the role of the kynurenine pathway in the pathophysiology of migraine].

Migraine is one of the most common forms of primary headaches, affecting a significant portion of the population. In addition to reducing the quality of life for those affected, the disease causes serious economic problems worldwide due to decreased productivity and lost work hours. The exact pathophysiology of migraine remains unclear to this day, and available therapeutic options are not satisfactory. The increasing prevalence and therapy-resistant cases call for precise mapping of the disease’s pathomechanism and the development of new therapeutic alternatives as soon as possible. Although our knowledge of the pathomechanism has long been centered primarily around serotonin, the kynurenine metabolic pathway has gained increasing attention in recent years. The kynurenine pathway of tryptophan metabolism plays a significant role in the pathophysiology of migraine due to its important function in regulating glutamatergic mechanisms. This metabolic pathway is responsible for the synthesis of numerous neuroprotective and neurotoxic metabolites. One of the end-products of the pathway is kynurenic acid, an endogenous ionotropic glutamate receptor antagonist. Experimental data supports that kynurenic acid plays an important role in the pathomechanism of migraine. Preclinical studies have demonstrated that kynurenic acid and its synthetic analogs are capable of inhibiting pathological processes occurring during migraine, making them potential targets for future drug research. Our human clinical studies have confirmed that the delicate balance maintained by neuroprotective and neurotoxic kynurenine metabolites is disrupted in migraine patients. This imbalance manifests in a significant decrease in the concentration of neuroprotective molecules and a significant increase in the concentration of neurotoxic molecules. Exploring the relationship between primary headache disorders and the kynurenine pathway of tryptophan metabolism may improve understanding of pathophysiology. Depressed kynurenine metabolism in migraine patients suggests a link with the gastrointestinal system, while synthetic analogs with better pharmacokinetics than kynurenic acid may offer new treatment perspectives. Orv Hetil. 2025; 166(23): 879–886.