Sokolov Alexey Y, Sivachenko Ivan B, Panteleev Sergey S, Lyubashina Olga A
Department of Neuropharmacology, Valdman Institute of Pharmacology, Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia.
Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, St. Petersburg, Russia.
Clin Exp Pharmacol Physiol. 2018 Jan;45(1):34-41. doi: 10.1111/1440-1681.12849. Epub 2017 Oct 4.
One way to expand the existing range of anti-migraine drugs seems to be the search for pharmacological agents with anti-cephalalgic properties among medicines approved for clinical indications other than migraine. Numerous experimental and clinical data imply that selective serotonin 5-HT3 receptor antagonists can be considered as potential anti-migraine agents. Therefore, the objective of our work was to examine the impact of selective 5-HT3 receptor blockade with granisetron on migraine-related nociceptive transmission within the spinal trigeminal nucleus (STN) and the ventroposteromedial nucleus of the thalamus (VPM). Using an electrophysiological model of trigemino-durovascular nociception in anaesthetised male Wistar rats, we evaluated the effects of intravenous administration of granisetron on ongoing firing and dural electrical stimulation-evoked responses of the spinal trigeminal and thalamic cells. Granisetron did not substantially affect responses of the STN and VPM neurons to electrical stimulation of the dura mater as well as did not cause steady changes in ongoing firing of the spinal trigeminal cells. The results obtained argue against the use of 5-HT3 receptor antagonists for treating migraine. These data also lead to the conclusion that in the absence of sustained sensitisation of neurons along the trigemino-thalamo-cortical pathway the role of 5-HT3 receptor-dependent mechanisms in serotonergic modulation of trigeminovascular nociceptive transmission can hardly be considered crucial.
拓展现有抗偏头痛药物种类的一种方法似乎是在已获批用于偏头痛以外临床适应症的药物中寻找具有抗头痛特性的药理剂。大量实验和临床数据表明，选择性5-羟色胺3（5-HT3）受体拮抗剂可被视为潜在的抗偏头痛药物。因此，我们研究的目的是检验格拉司琼选择性阻断5-HT3受体对脊髓三叉神经核（STN）和丘脑腹后内侧核（VPM）内偏头痛相关伤害性传递的影响。利用麻醉的雄性Wistar大鼠的三叉神经-硬脑膜血管伤害感受电生理模型，我们评估了静脉注射格拉司琼对脊髓三叉神经和丘脑细胞的自发放电以及硬脑膜电刺激诱发反应的影响。格拉司琼对STN和VPM神经元对硬脑膜电刺激的反应没有实质性影响，也没有使脊髓三叉神经细胞的自发放电产生稳定变化。所得结果不支持使用5-HT3受体拮抗剂治疗偏头痛。这些数据还得出结论，在三叉神经-丘脑-皮质通路的神经元没有持续敏化的情况下，5-HT3受体依赖性机制在5-羟色胺能调节三叉神经血管伤害性传递中的作用很难被认为是至关重要的。
