Calcitonin gene-related peptide (CGRP), substance P and dural mast cells are main contributors in neurogenic inflammation underlying migraine pathophysiology. Modulation of endocannabinoid system attenuates migraine pain, but its mechanisms of action remain unclear. We investigated receptor mechanisms mediating anti-neuroinflammatory effects of endocannabinoid system modulation in in vivo migraine model and ex vivo hemiskull preparations in rats. To induce acute model of migraine, a single dose of nitroglycerin was intraperitoneally administered to male rats. Moreover, isolated ex vivo rat hemiskulls were prepared to study CGRP and substance P release from meningeal trigeminal afferents. We used methanandamide (cannabinoid agonist), rimonabant (cannabinoid receptor-1 CB1 antagonist), SR144528 (CB2 antagonist) and capsazepine (transient receptor potential vanilloid-1 TRPV1 antagonist) to explore effects of endocannabinoid system modulation on the neurogenic inflammation, and possible involvement of CB1, CB2 and TRPV1 receptors during endocannabinoid effects. Methanandamide attenuated nitroglycerin-induced CGRP increments in in vivo plasma, trigeminal ganglia and brainstem and also in ex vivo hemiskull preparations. Methanandamide also alleviated enhanced number and degranulation of dural mast cells induced by nitroglycerin. Rimonabant, but not capsazepine or SR144528, reversed the attenuating effects of methanandamide on CGRP release in both in vivo and ex vivo experiments. Additionally, SR144528, but not rimonabant or capsazepine, reversed the attenuating effects of methanandamide on dural mast cells. However, neither nitroglycerin nor methanandamide changed substance P levels in both in vivo and ex vivo experiments. Methanandamide modulates CGRP release in migraine-related structures via CB1 receptors and inhibits the degranulation of dural mast cells through CB2 receptors. Selective ligands targeting CB1 and CB2 receptors may provide novel and effective treatment strategies against migraine.
The strong magnetic field properties of magnets have led to their use in many modern technologies, as well as in the fields of medicine and dentistry. Neodymium magnets are a powerful type of magnet that has been the subject of recent research. This review provides a brief explanation of the definition, history, and characteristics of rare earth magnets. In addition, a broad overview of results obtained in studies performed to date on the effects of magnets, and neodymium magnets in particular, on body systems, tissues, organs, diseases, and treatment is provided. Though they are used in the health sector in various diagnostic devices and as therapeutic tools, there is some potential for harmful effects, as well as the risk of accident. The research is still insufficient; however, neodymium magnets appear to hold great promise for both diagnostic and therapeutic purposes.
Dünya çapında 19 Mart 2020 itibariyle 170'in üzerinde ülkeyi saran COVID-19 enfeksiyonu neticesinde pozitif vakaların ve ölüm haberlerinin hızla yayıldığı herkes tarafından endişe ile takip edilmektedir. Sosyal medya ve internet ortamında çok ciddi düzeyde bilgi birikimi ortaya çıkmıştır. Bu çalışmanın amacı an itibariyle elde edilen veriler ışığında tüm dünya ülkelerinde enfeksiyon etkileri ve süreci hakkında genel yapıyı özetleyen istatistiki bilgiler sunmak ve enfeksiyon ölçütlerinin günlük değişimini modellemektir. Elde edilen sonuçlar değerlendirildiğinde, birikimli (kümülatif) pozitif vaka sayısı, birikimli ölüm sayısı ve diğer bazı ölçütlerin ülkelere göre seyrinin aynı olmadığı, süreci en iyi kontrol eden ülkelerin başında Almanya ve Güney Kore'nin geldiği, Türkiye' nin sürecinin ilk 10 günlük süreç itibariyle hızlı yayılım gösteren ülkelere benzediği görüldü. Ayrıca Türkiye için 20-29 Mart 2020 arasında ortaya çıkabilecek pozitif vaka sayısı ve birikimli ölüm sayıları tahmin edildiğinde 20 Mart itibariyle pozitif vaka sayısının sayının 550 civarında, an itibariyle 4 olan ölüm sayısının 11 olacağı öngörülmüştür.
Background Calcitonin gene-related peptide release in trigeminovascular system is a pivotal component of neurogenic inflammation underlying migraine pathophysiology. Transient receptor potential channels and voltage-gated KCNQ/Kv7 potassium channels expressed throughout trigeminovascular system are important targets for modulation of calcitonin gene-related peptide release. We investigated the effects of certain transient receptor potential (TRP) channels the vanilloid 1 and 4 (TRPV1 and TRPV4), the ankyrin 1 (TRPA1), and metastatin type 8 (TRPM8), and voltage-gated potassium channel (Kv7) opener retigabine on calcitonin gene-related peptide release from peripheral (dura mater and trigeminal ganglion) and central (trigeminal nucleus caudalis) trigeminal components of rats. Methods The experiments were carried out using well-established in-vitro preparations (hemiskull, trigeminal ganglion and trigeminal nucleus caudalis) from male Wistar rats. Agonists and antagonists of TRPV1, TRPV4, TRPA1 and TRPM8 channels, and also retigabine were tested on the in-vitro release of calcitonin gene-related peptide. Calcitonin gene-related peptide concentrations were measured using enzyme-linked immunosorbent assay. Results Agonists of these transient receptor potential channels induced calcitonin gene-related peptide release from hemiskull, trigeminal ganglion and trigeminal nucleus caudalis, respectively. The transient receptor potential channels-induced calcitonin gene-related peptide releases were blocked by their specific antagonists and reduced by retigabine. Retigabine also decreased basal calcitonin gene-related peptide releases in all preparations. Conclusion Our findings suggest that favorable antagonists of these transient receptor potential channels, or Kv7 channel opener retigabine may be effective in migraine therapy by inhibiting neurogenic inflammation that requires calcitonin gene-related peptide release.
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