Sokolov Alexey Y, Lyubashina Olga A, Sivachenko Ivan B, Panteleev Sergey S
Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Nab. Makarova, St. Petersburg 199034, Russia; Department of Neuropharmacology, Valdman Institute of Pharmacology, First St. Petersburg Pavlov State Medical University, 6/8 Lev Tolstoy Street, St. Petersburg 197022, Russia.
Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Nab. Makarova, St. Petersburg 199034, Russia.
Eur J Pharmacol. 2014 May 15;731:58-64. doi: 10.1016/j.ejphar.2014.03.006. Epub 2014 Mar 18.
Migraine and tension-type headache (TTH) are the most common forms of primary headaches. A general key mechanism underlying development of both the diseases is the trigeminal system activation associated with the ascending nociceptive transmission via the trigemino-thalamo-cortical pathway. The ventroposteromedial (VPM) nucleus is a key thalamic structure, receiving afferent inflow from the craniofacial region; it holds the third-order neurons responsible for conveying sensory information from the extra- and intracranial nociceptors to the cortex. The VPM is currently seen as a therapeutic target for various antimigraine medications, which is shown to reduce the VPM neuronal excitability. A non-opioid analgesic metamizole is widely used in some countries for acute treatment of migraine or TTH. However, the precise mechanisms underlying anticephalgic action of metamizole remain unclear. The objective of our study performed in the rat model of trigemino-durovascular nociception was to evaluate the effects of intravenously administered metamizole on ongoing and evoked firing of the dura-sensitive VPM neurons. The experiments were carried out on rats under urethane-chloralose anesthesia. Cumulative administration of metamizole (thrice-repeated intravenous infusion of 150 mg/kg performed 30 min apart) in 56% of cases produced a suppression of both the ongoing activity of the thalamic VPM neurons and their responses to dural electrical stimulation. Although the inhibitory effect was prevailing, a number of VPM neurons were indifferent to the administration of metamizole. These data suggest that one of the main components of neural mechanism underlying anticephalgic action of metamizole is suppression of the thalamo-cortical nociceptive transmission associated with trigemino-vascular activation.
偏头痛和紧张型头痛（TTH）是原发性头痛最常见的形式。这两种疾病发生的一个共同关键机制是三叉神经系统激活，它与通过三叉神经 - 丘脑 - 皮质通路的伤害性上行传导有关。腹后内侧（VPM）核是丘脑的一个关键结构，接收来自颅面部区域的传入信息流；它包含负责将来自颅外和颅内伤害感受器的感觉信息传递到皮质的三级神经元。目前，VPM被视为各种抗偏头痛药物的治疗靶点，这些药物可降低VPM神经元的兴奋性。一种非阿片类镇痛药安乃近在一些国家被广泛用于偏头痛或TTH的急性治疗。然而，安乃近止痛作用的确切机制仍不清楚。我们在三叉神经 - 硬脑膜血管伤害感受大鼠模型中进行的研究目的是评估静脉注射安乃近对硬脑膜敏感的VPM神经元的自发放电和诱发放电的影响。实验在乌拉坦 - 氯醛糖麻醉的大鼠身上进行。在56%的病例中，累积给予安乃近（每隔30分钟重复静脉输注150 mg/kg三次）可抑制丘脑VPM神经元的自发放电活动及其对硬脑膜电刺激的反应。尽管抑制作用占主导，但一些VPM神经元对安乃近的给药无反应。这些数据表明，安乃近止痛作用的神经机制的主要成分之一是抑制与三叉神经 - 血管激活相关的丘脑 - 皮质伤害性传递。
