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.