Kynurenine Metabolites and Migraine: Experimental Studies and Therapeutic Perspectives

Abstract

Migraine is one of the commonest neurological disorders. Despite intensive research, its exact pathomechanism is still not fully understood and effective therapy is not always available. One of the key molecules involved in migraine is glutamate, whose receptors are found on the first-, second- and third-order trigeminal neurones and are also present in the migraine generators, including the dorsal raphe nucleus, nucleus raphe magnus, locus coeruleus and periaqueductal grey matter. Glutamate receptors are important in cortical spreading depression, which may be the electrophysiological correlate of migraine aura. The kynurenine metabolites, endogenous tryptophan metabolites, include kynurenic acid (KYNA), which exerts a blocking effect on ionotropic glutamate and α7-nicotinic acetylcholine receptors. Thus, KYNA and its derivatives may act as modulators at various levels of the pathomechanism of migraine. They can give rise to antinociceptive effects at the periphery, in the trigeminal nucleus caudalis, and may also act on migraine generators and cortical spreading depression. The experimental data suggest that KYNA or its derivatives might offer a novel approach to migraine therapy.

Influence of ovarian hormones on occurrence of cortical spreading depression and its suppression of by L-kynurenine in rat

“…Furthermore, L-kynurenine is more efficient in suppressing CSD when levels of progesterone are high. Taken together, these results emphasize the complex role of sex hormones in migraine and may open novel perspectives for its preventive treatment [2]. …”

Tryptophan Catabolites and Migraine

“…Since Sicuteri's observations about the involvement of 5HT in migraine pathomechanism [101] research focused on the 5HT pathway of TRP metabolism, although in the past years the KP's involvement was also confirmed [4,128].…”

Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood–brain barrier permeability

“…Furthermore, published data indicate that CSD results in a disruption of the BBB 7,19. Since NMDARs play a decisive role in the generation and propagation of CSD,3,20 and data are accumulating which suggest that endogenous KYNA may act as a modulator at various levels of the pathomechanism of migraine,21 it seemed plausible to study the effects on CSD of exogenously administered KYNA.…”