uzspbgmuУчёные записки Первого Санкт-Петербургского государственного медицинского университета имени академика И. П. ПавловаThe Scientific Notes of the Pavlov University1607-41812541-8807Academician I.P. Pavlov First St. Petersburg State Medical University10.24884/1607-4181-2022-29-3-55-64uzspbgmu-901Research ArticleОРИГИНАЛЬНЫЕ РАБОТЫORIGINAL PAPERSВентральное заднемедиальное ядро таламуса как нейроанатомическая мишень антицефалгического действия вальпроевой кислоты и метамизолаVentral posteromedial nucleus of the thalamus as a neuroanatomical target for the anticephalalgic action of valproic acid and metamizolehttps://orcid.org/0000-0002-6141-486XСоколовА. Ю.SokolovA. Yu.

доктор медицинских наук, доцент, зав. отделом нейрофармакологии Института фармакологии им. А. В. Вальдмана, профессор кафедры фармакологии, 197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8;

старший научный сотрудник лаборатории кортико-висцеральной физиологии, Санкт-Петербург

 

Dr. of Sci. (Med.), Associate Professor, Head of the Department of Neuropharmacology, Valdman Institute of Pharmacology, Professor of the Department of Pharmacology;

Senior Research Fellow of the Laboratory of Cortico-Visceral Physiology, 

 

alexey.y.sokolov@gmail.comhttps://orcid.org/0000-0002-6296-4628ЛюбашинаО. А.LyubashinaO. A.

ведущий научный сотрудник лаборатории экспериментальной фармакологии и терапии боли отдела нейрофармакологии Института фармакологии им. А. В. Вальдмана;

доктор биологических наук, зав. лабораторией кортико-висцеральной физиологии,

Санкт-Петербург

Leading Researcher of the Laboratory of Experimental Pharmacology and Therapy of Pain, Department of Neuropharmacology, Valdman Institute of Pharmacology;

Dr. of Sci. (Biol.), Head of the Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences,

Saint Petersburg

laglo2009@yandex.ruФедеральное государственное бюджетное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное учреждение науки «Институт физиологии имени И. П. Павлова» Российской академии наукРоссияPavlov University; Pavlov Institute of Physiology of the Russian Academy of SciencesRussian Federation2022130720222935564Copyright © Соколов А.Ю., Любашина О.А., 20222022Соколов А.Ю., Любашина О.А.Sokolov A.Y., Lyubashina O.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sci-notes.ru/jour/article/view/901Введение

Введение. Вальпроевая кислота и метамизол широко используются в лечении первичных головных болей, однако, несмотря на доказанную клиническую эффективность, нейрофизиологический механизм их терапевтического действия недостаточно изучен. Вентральное заднемедиальное ядро таламуса (ВЗМЯ) служит высшим надсегментарным релейным центром для передачи восходящей ноцицептивной информации от краниальных структур в кору и рассматривается как одна из вероятных нейроанатомических мишеней действия антицефалгических препаратов.

Цель – изучение влияния вальпроата и метамизола на возбудимость нейронов ВЗМЯ.

Методы и материалы

Методы и материалы. В острых контролируемых опытах на наркотизированных крысах (n=31) оценивали эффект внутривенного назначения в кумулятивном режиме (трехкратное введение фиксированной дозы через каждые 30 мин) вальпроата (n=8, 100 мг/кг · 3) и метамизола (n=16, 150 мг/кг · 3) на внеклеточно зарегистрированную фоновую и вызванную электростимуляцией dura mater активность конвергентных клеток ВЗМЯ.

Результаты

Результаты. Вальпроат во всех опытах значимо угнетал спонтанную активность нейронов ВЗМЯ и их ответы на дуральное электрораздражение. Метамизол обладал аналогичным действием более чем в половине случаев, тогда как 44 % исследованных таламических клеток не реагировали на его инфузию.

Заключение

Заключение. Одним из компонентов нейрофизиологического механизма антицефалгического действия вальпроевой кислоты и метамизола может являться торможение ноцицептивной трансмиссии на уровне таламуса за счет подавления возбудимости менингеально-чувствительных нейронов ВЗМЯ. 

Introduction

Introduction. Valproic acid and metamizole are widely used in the treatment of primary headaches. However, despite the drugs’ proven clinical efficacy, the neurophysiological mechanisms underlying their therapeutic action are poorly understood. The ventral posteromedial nucleus of the thalamus (VPM) serves as the highest suprasegmental relay center for transmitting ascending nociceptive information from the cranial structures to the cerebral cortex and is considered as a potential neuroanatomical target for anticephalalgic drugs.

The objective of the study was to evaluate the action of valproate and metamizole on the excitability of the VPM thalamic neurons.

Methods and materials

Methods and materials. In acute controlled experiments on anesthetized rats (n=31), we studied the action of cumulative dosing (three fixed dose injections every 30 minutes) of intravenously administered valproate (n=8, 100 mg/kg x 3) or metamizole (n=16,150 mg/kg · 3) on extracellularly recorded background and dura mater electrical stimulation-evoked activities of the convergent VPM neurons. Results. In all experiments, intravenous valproate significantly inhibited both background activity of the VPM neurons and their responses to dural electrostimulation. Metamizole had a similar action in more than half of the cases, whereas 44 % of the examined thalamic cells (7 out of 16) did not react to its infusion.

Conclusion

Conclusion. One of the main neurophysiological mechanisms underlying anticephalalgic action of valproic acid and metamizole may be inhibition of the nociceptive transmission at the thalamic level due to the drugs-induced suppression of the meningeal-sensitive VPM neurons excitability. 

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The authors declare that there are no conflicts of interest present.