Kynurenine Metabolites and Migraine: Experimental Studies and Therapeutic Perspectives

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

Investigating the effect of grit trait on performance and success in Hungarian athlete’s sample

BackgroundThe aim of the present study is to translate the Grit questionnaire into Hungarian and validate specifically within the context of sports. The second goal is to assess the questionnaire in Hungarian as a pilot study in the athlete population and to compare the grit trait with the coaches’ athlete evaluation.MethodsTwo hundred and sixty nine athletes, including 40 national team players, took part in the study, with an average age of 18.17 years (SD = 5.51). For the preliminary assessment, the Cloninger Temperament and Character Questionnaire (TCI-RH) was used; the coaches’ athlete evaluation was modeled on a talent map.ResultsThe confirmatory factor analysis confirmed the fit of the two-factor structure, and the internal reliability of the questionnaire scales also proved to be adequate. 2. There is no relationship between adolescents’ perceived grit and coach ratings. 3. The national team players achieved a higher grit score.ConclusionBased on the psychometric indicators, the validity and reliability of the questionnaire proved to be adequate. Therefore, it is applicable and useful for psychological practitioners and researchers in the Hungarian population within the context of sports

Chemokine receptor V Delta32 deletion in multiple sclerosis patients in Csongrad County in Hungary and the North-Bacska region in Serbia

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Modulatory effect of synthetic kynurenic acid derivatives on the nitroglycerin-induced trigeminal activation and sensitization in rats

Migraine is one of the most common neurological disorders. Its pathomechanism is only partially known and therapy is not always effective. In migraine, activation of trigeminal system plays an important role involving peptides/enzymes like calcitonin gene-related peptide (CGRP), neuronal nitric oxide synthase (nNOS) and calcium/calmodulin-dependent protein kinase II α (CaMKIIα) and glutamate and α7-nicotinic acetylcholine (α7-nACh) receptors. Kynurenic acid is an endogenous antagonist of the above mentioned receptors, but its poor ability to cross the blood-brain barrier limits its therapeutic potential, therefore in our experiments we investigated effect of its pro-drug, L-kynurenine (L-KYN) combined with probenecid (PROB) and two newly synthesized kynurenic acid amides (KYNAa1, KYNAa2) on kynurenic acid concentration of the central nervous system in rats and on morphological and behavioural changes induced by systemic administration of nitroglycerin (NTG), an animal model of migraine. Our results showed that kynurenic acid concentration in cervical part of spinal trigeminal nucleus pars caudalis (C1-C2) - where most of the trigeminal nociceptors convey - was significantly increased one hour after L-KYN-PROB. Moreover, KYNAa2 also enhanced kynurenic acid levels suggesting that this new derivative, at least partially, transforms to kynurenic acid resulting in a possible direct and indirect action in the central nervous system. The significant decrease of CGRP and increase of c-Fos, nNOS and CaMKIIα four hours after NTG treatment in C1-C2 measured by immunohistochemistry and Western blotting reflect the activation and sensitization of the trigeminal system. These changes were attenuated by the pre-treatment with L-KYN-PROB, KYNAa1 and in a dose-dependent manner with KYNAa2 probably due to their effects on the target receptors of kynurenic acid located in the peripheral and central part of the trigeminal system. The NTG-induced lower ambulation distance demonstrated by Open Field Test may indicate pain condition in rats, which can not be observed after pre-treatment with KYNAa2. Furthermore, the KYNAa2 administration lowers the basic ambulation distance which can reflect its central effect. Our results suggest that by modulating the activation and sensitization of the trigeminal system in animals, kynurenic acid or its derivatives can be potential drug candidates in the treatment of headaches

Models of Trigeminal Activation: Is There an Animal Model of Migraine?

Migraine, recognized as a severe headache disorder, is widely prevalent, significantly impacting the quality of life for those affected. This article aims to provide a comprehensive review of the application of animal model technologies in unraveling the pathomechanism of migraine and developing more effective therapies. It introduces a variety of animal experimental models used in migraine research, emphasizing their versatility and importance in simulating various aspects of the condition. It details the benefits arising from the utilization of these models, emphasizing their role in elucidating pain mechanisms, clarifying trigeminal activation, as well as replicating migraine symptoms and histological changes. In addition, the article consciously acknowledges the inherent limitations and challenges associated with the application of animal experimental models. Recognizing these constraints is a fundamental step toward fine-tuning and optimizing the models for a more accurate reflection of and translatability to the human environment. Overall, a detailed and comprehensive understanding of migraine animal models is crucial for navigating the complexity of the disease. These findings not only provide a deeper insight into the multifaceted nature of migraine but also serve as a foundation for developing effective therapeutic strategies that specifically address the unique challenges arising from migraine pathology

Evaluation of c-Fos immunoreactivity in the rat brainstem nuclei relevant in migraine pathogenesis after electrical stimulation of the trigeminal ganglion

Migraine is a common neurological condition, causing high disability, but the pathomechanism of the disease is not yet fully understood. Activation of the trigeminovascular system could play a crucial role in the manifestation of the symptoms, but initial step of this activation remains unknown. Functional imaging studies have revealed that certain brainstem areas, referred to as migraine generators, are activated during a migraine attack, including the dorsal raphe, the periaqueductal gray, the locus coeruleus, and the nucleus raphe magnus. However, the studies performed to date have not demonstrated whether this activation is a trigger or a consequence of the migraine attack. With the aim of evaluating the functional relationship between activation of the trigeminal system and migraine generators, we examined the changes in c-Fos immunoreactivity in the above-mentioned nuclei after stimulation of the trigeminal ganglion, an animal model for trigeminovascular activation. The stimulation led to significant increases in the number of c-Fos immunoreactive cells in the nucleus raphe magnus and in the caudal part of the spinal trigeminal nucleus, 2 and 4 h after the stimulation. Activation of the trigeminal system failed to exhibit uniform activation of the brain stem nuclei related to migraine. Our results suggest that the activation of the trigeminal system in the rat by electrical stimulation of the trigeminal ganglion leads to the activation of the descending pain modulatory system, but not to the activation of “migraine generator” nuclei. Therefore, the activity pattern seen in functional studies may reflect a unique feature, exclusively present in migraine