The role of neurogenic inflammation and estradiol in migraine: animal experimental data

A migraine is a neurological condition that can cause various symptoms. Being three times more common in women than men, it has a clear sexual dimorphism, thus estrogen may play an important role in the appearance attacks. Despite continuous progress in migraine research, its exact pathomechanism is still unknown; however, the activation and sensitization of the trigeminal system (TS) play an essential role. One of the animal models developed to mimic the events during migraine is the topical application of inflammatory soup (IS) on the dura mater. We used this method to evaluate various activation and sensitization markers in the trigeminal nucleus caudalis (TNC) and the possible modulatory effect of sumatriptan. a well-known antimigraine drug acting on 5HT1B/1D receptors and kynurenic acid (KYNA), an endogenous molecule of tryptophan metabolism, an N-methyl-D-aspartate (NMDA) antagonist. We also investigated the effect of chronic 17β-estradiol pretreatment on the trigeminal pain-related behavior and activation of trigeminal second-order neurons at the level of TNC in another model of headache, the orofacial formalin test. Compared to placebo the topical IS application on the dura increased the expression of the activation and sensitization markers in the TNC, namely calcitonin gene-related peptide (CGRP), transient receptor potential vanilloid-1 receptor (TRPV1), and neuronal nitric oxide synthase (nNOS), which was attenuated by sumatriptan and KYNA, suggesting the involvement of 5-HT1B/1D and NMDA receptors in the development of neurogenic inflammation and thus in migraine attacks. Our results from the orofacial formalin test demonstrated, that chronic 17β-estradiol treatment had a strong pronociceptive effect on orofacial formalin-induced inflammatory pain, which was demonstrated by both by behavioral changes and increased c-Fos expression in the TNC. This suggests a modulatory action of estradiol on head pain through estrogen receptors, which are present throughout the TS

New cases of probable skeletal tuberculosis from the Neolithic period in Hungary : a morphological study

The aim of this study is to present new data on the occurrence of tuberculosis (TB) in the Neolithic period of Hungary. The authors present results of the paleopathological investigation of skeletal remains from the Tisza culture tell settlement of Vésztô-Mágor, one of the largest Neolithic tells of the Great Hungarian Plain. The remains of 30 individuals were examined using standard macromorphological methods of bioarchaeology. Before the paleopathological examination of the series, sex and age at death of individuals and state of preservation of the observable skeletal elements were also recorded. In spite of the poor state of preservation, the osteoarchaeological series of Vésztô-Mágor showed a wide range of paleopathological alterations: skeletal traces of degenerative articular changes, traumas, haematological and infectious diseases were observed. This presentation focuses on 4 probable tuberculous cases. Most of the detected alterations (rib lesions, superficial vertebral changes/hypervascularisation and endocranial alterations) can be considered as atypical or early-stage TB lesions. Although a positive correlation seems to exist between these alterations and TB, they are not always pathognomonic to tuberculosis. These results contribute to improving our knowledge on the occurrence of TB in prehistoric populations of Hungary

All Roads Lead to the Gut: The Importance of the Microbiota and Diet in Migraine

Migraine, a prevalent neurological condition and the third most common disease globally, places a significant economic burden on society. Despite extensive research efforts, the precise underlying mechanism of the disease remains incompletely comprehended. Nevertheless, it is established that the activation and sensitization of the trigeminal system are crucial during migraine attacks, and specific substances have been recognized for their distinct involvement in the pathomechanism of migraine. Recently, an expanding body of data indicates that migraine attacks can be prevented and treated through dietary means. It is important to highlight that the various diets available pose risks for patients without professional guidance. This comprehensive overview explores the connection between migraine, the gut microbiome, and gastrointestinal disorders. It provides insight into migraine-triggering foods, and discusses potential diets to help reduce the frequency and severity of migraine attacks. Additionally, it delves into the benefits of using pre- and probiotics as adjunctive therapy in migraine treatment

TRP Channels : Recent Development in Translational Research and Potential Therapeutic Targets in Migraine

Migraine is a chronic neurological disorder that affects approximately 12% of the population. The cause of migraine headaches is not yet known, however, when the trigeminal system is activated, neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P (SP) are released, which cause neurogenic inflammation and sensitization. Advances in the understanding of migraine pathophysiology have identified new potential pharmacological targets. In recent years, transient receptor potential (TRP) channels have been the focus of attention in the pathophysiology of various pain disorders, including primary headaches. Genetic and pharmacological data suggest the role of TRP channels in pain sensation and the activation and sensitization of dural afferents. In addition, TRP channels are widely expressed in the trigeminal system and brain regions which are associated with the pathophysiology of migraine and furthermore, co-localize several neuropeptides that are implicated in the development of migraine attacks. Moreover, there are several migraine trigger agents known to activate TRP channels. Based on these, TRP channels have an essential role in migraine pain and associated symptoms, such as hyperalgesia and allodynia. In this review, we discuss the role of the certain TRP channels in migraine pathophysiology and their therapeutic applicability

Exploring the Tryptophan Metabolic Pathways in Migraine-Related Mechanisms

Migraine is a complex neurovascular disorder, which causes intense socioeconomic problems worldwide. The pathophysiology of disease is enigmatic; accordingly, therapy is not sufficient. In recent years, migraine research focused on tryptophan, which is metabolized via two main pathways, the serotonin and kynurenine pathways, both of which produce neuroactive molecules that influence pain processing and stress response by disturbing neural and brain hypersensitivity and by interacting with molecules that control vascular and inflammatory actions. Serotonin has a role in trigeminal pain processing, and melatonin, which is another product of this pathway, also has a role in these processes. One of the end products of the kynurenine pathway is kynurenic acid (KYNA), which can decrease the overexpression of migraine-related neuropeptides in experimental conditions. However, the ability of KYNA to cross the blood-brain barrier is minimal, necessitating the development of synthetic analogs with potentially better pharmacokinetic properties to exploit its therapeutic potential. This review summarizes the main translational and clinical findings on tryptophan metabolism and certain neuropeptides, as well as therapeutic options that may be useful in the prevention and treatment of migraine

Steuerung von Küstenschutzelementen an Tideflüssen als Grundlage für ein Hochwasser- und Risikomanagement

[no abstract

Ion Channel Disturbances in Migraine Headache: Exploring the Potential Role of the Kynurenine System in the Context of the Trigeminovascular System

Migraine is a primary headache disorder, which is an enormous burden to the healthcare system. While some aspects of the pathomechanism of migraines remain unknown, the most accepted theory is that activation and sensitization of the trigeminovascular system are essential during migraine attacks. In recent decades, it has been suggested that ion channels may be important participants in the pathogenesis of migraine. Numerous ion channels are expressed in the peripheral and central nervous systems, including the trigeminovascular system, affecting neuron excitability, synaptic energy homeostasis, inflammatory signaling, and pain sensation. Dysfunction of ion channels could result in neuronal excitability and peripheral or central sensitization. This narrative review covers the current understanding of the biological mechanisms leading to activation and sensitization of the trigeminovascular pain pathway, with a focus on recent findings on ion channel activation and modulation. Furthermore, we focus on the kynurenine pathway since this system contains kynurenic acid, which is an endogenous glutamate receptor antagonist substance, and it has a role in migraine pathophysiology

Tuberkulózissal összefüggésbe hozható endocranialis csontelváltozások vizsgálata a Robert J. Terry Anatomical Skeletal Collection-ben (Washington, DC, USA)

Despite significant advances in the fight against tuberculosis (TB), it still presents a global health emergency. Therefore, a renewed interest and funding to the research of the disease and of its aetiological agents, including the palaeopathological diagnostics for TB, has sparked since the late 20th century to eliminate or at least control TB in the future. Traditionally, the palaeopathological diagnosis of TB relies on the identification of pathological lesions in the skeleton. Although a number of endocranial bony alterations, namely abnormally pronounced digital impressions (APDIs), periosteal appositions (PAs), abnormal blood vessel impressions (ABVIs), and granular impressions (GIs) have been attributed to TB in the palaeopathological literature, the diagnostic value of these lesions has more recently been questioned, as their precise aetiology is still a matter of controversy, and similar or even the same morphological features can be found in non-TB-related cases. In the last three decades, the Terry Collection has been used to define and refine palaeopathological diagnostic criteria for TB, however, the possible TB-associated endocranial alteration types were beyond the scope of the aforementioned research projects. To expand our knowledge and understanding about the development of the four probable TB-related endocranial alteration types and to improve their palaeopathological interpretation, as well as to contribute to strengthening their diagnostic value in the identification of TB in human osteoarchaeological material, a detailed investigation was performed on all individuals recorded to have died of TB in the Terry Collection (TB group), and on a control group consisting of randomly selected specimens from the remaining skeletons of the Terry Collection, identified to have died of causes other than TB (NTB group). The evaluation of the selected skeletons focused on the macromorphological characteristics and on the frequencies of the possible TB-associated endocranial alteration types, as well as of their co-occurrence with each other and with non-endocranial bony changes probably related to TB. All the examined endocranial alteration types, as well as their association with each other and with non-endocranial lesions occurred significantly more frequently in the TB group compared to the NTB group; therefore, all of them can be used as diagnostic criteria for TB in the palaeopathological practice, especially when they simultaneously occur with each other and/or with probable TB-related non-endocranial bony changes. Our findings fit in with those of previous studies concerning the specificity of the examined lesions: APDIs, PAs, and ABVIs cannot be considered as pathognomonic features of TB and have a weaker diagnostic value compared to GIs, which are TB-specific alterations. In summary, our results contribute to facilitating the establishment of a more reliable and accurate palaeopathological diagnosis of TB