Lyubashina Olga A, Panteleev Sergey S, Sokolov Alexey Y
Laboratory of Cortico-Visceral Physiology, Pavlov Institute of Physiology of the Russian Academy of Sciences, 6 Nab. Makarova, Saint Petersburg, 199034, Russia.
Department of Neuropharmacology, Valdman Institute of Pharmacology, First Saint-Petersburg Pavlov State Medical University, 6/8 Lev Tolstoy Street, Saint Petersburg, 197022, Russia.
J Neural Transm (Vienna). 2017 Feb;124(2):171-183. doi: 10.1007/s00702-016-1626-2. Epub 2016 Sep 27.
Electrical stimulation of the greater occipital nerve (GON) has recently shown promise as an effective non-pharmacological prophylactic therapy for drug-resistant chronic primary headaches, but the neurobiological mechanisms underlying its anticephalgic action are not elucidated. Considering that the spinal trigeminal nucleus (STN) is a key segmental structure playing a prominent role in pathophysiology of headaches, in the present study we evaluated the effects of GON electrical stimulation on ongoing and evoked firing of the dura-sensitive STN neurons. The experiments were carried out on urethane/chloralose-anesthetized, paralyzed and artificially ventilated male Wistar rats. Extracellular recordings were made from 11 neurons within the caudal part of the STN that received convergent input from the ipsilateral facial cutaneous receptive fields, dura mater and GON. In each experiment, five various combinations of the GON stimulation frequency (50, 75, 100 Hz) and intensity (1, 3, 6 V) were tested successively in 10 min interval. At all parameter sets, preconditioning GON stimulation (250 ms train of pulses applied before each recording) produced suppression of both the ongoing activity of the STN neurons and their responses to electrical stimulation of the dura mater. The inhibitory effect depended mostly on the GON stimulation intensity, being maximally pronounced when a stimulus of 6 V was applied. Thus, the GON stimulation-induced inhibition of trigeminovascular nociceptive processing at the level of STN has been demonstrated for the first time. The data obtained can contribute to a deeper understanding of neurophysiological mechanisms underlying the therapeutic efficacy of GON stimulation in primary headaches.
最近，电刺激枕大神经（GON）已显示出有望成为一种有效的非药物预防性疗法，用于治疗耐药性慢性原发性头痛，但尚未阐明其止痛作用背后的神经生物学机制。鉴于三叉神经脊束核（STN）是在头痛病理生理学中起重要作用的关键节段性结构，在本研究中，我们评估了GON电刺激对硬脑膜敏感的STN神经元持续放电和诱发放电的影响。实验在经乌拉坦/氯醛糖麻醉、麻痹并进行人工通气的雄性Wistar大鼠身上进行。对STN尾部的11个神经元进行细胞外记录，这些神经元接受来自同侧面部皮肤感受野、硬脑膜和GON的汇聚输入。在每个实验中，以10分钟的间隔依次测试GON刺激频率（50、75、100Hz）和强度（1、3、6V）的五种不同组合。在所有参数设置下，预处理的GON刺激（在每次记录前施加250ms的脉冲串）均能抑制STN神经元的持续活动及其对硬脑膜电刺激的反应。这种抑制作用主要取决于GON刺激强度，当施加6V刺激时最为明显。因此，首次证明了GON刺激在STN水平对三叉神经血管伤害性处理的抑制作用。所获得的数据有助于更深入地理解GON刺激在原发性头痛治疗效果背后的神经生理机制。
