Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period

Abstract Background Altered glutamatergic neurotransmission and neuropeptide levels play a central role in migraine pathomechanism. Previously, we confirmed that kynurenic acid, an endogenous antagonist, was able to decrease the expression of pituitary adenylate cyclase-activating polypeptide 1–38, with known migraine-inducing properties. Hence, our aim reveal peripheral kynurenine pathway (KP) episodic migraineurs. We focused on complete tryptophan (Trp) catabolism, which comprises serotonin melatonin routes addition metabolites. investigated relationship between metabolic alterations clinical characteristics patients. Methods Female patients aged 25 50 years ( n = 50) healthy control subjects 34) participated this study. Blood samples were collected from cubital veins (during both interictal/ictal periods migraineurs, 47/12, respectively). 12 metabolites Trp determined by neurochemical measurements (UHPLC-MS/MS). Results Plasma concentrations most remarkably decreased interictal period migraineurs compared subjects, especially without aura (MWoA) subgroup: p < 0.025), L-kynurenine 0.001), acid 0.016), anthranilic 0.007), picolinic 0.03), 5-hydroxy-indoleaceticacid (p 0.025) 0.023). Several showed tendency elevate during ictal phase, but significant only cases MWoA In same subgroup, higher identified whose headache severe not related their menstruation cycle. Negative linear correlation detected xanthurenic acid/melatonin attack frequency. Positive associations found 3-hydroxykynurenine beginning attacks, just as last before sampling. Conclusions Our results suggest there is widespread imbalance manifests completely depressed catabolism period. It might act trigger for attack, contributing glutamate excess induced neurotoxicity generalised hyperexcitability. This data can draw attention relevance KP migraine.