A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Int J Mol Sci. 2022 Oct 20;23(20):12590. doi: 10.3390/ijms232012590.
Stroke can be followed by immediate severe headaches. As headaches are initiated by the activation of trigeminal meningeal afferents, we assessed changes in the activity of meningeal afferents in mice subjected to cortical photothrombosis. Cortical photothrombosis induced ipsilateral lesions of variable sizes that were associated with contralateral sensorimotor impairment. Nociceptive firing of mechanosensitive Piezo1 channels, activated by the agonist Yoda1, was increased in meningeal afferents in the ischemic hemispheres. These meningeal afferents also had a higher maximal spike frequency at baseline and during activation of the mechanosensitive Piezo1 channel by Yoda1. Moreover, in these meningeal afferents, nociceptive firing was active during the entire induction of transient receptor potential vanilloid 1 (TRPV1) channels by capsaicin. No such activation was observed on the contralateral hemi-skulls of the same group of mice or in control mice. Our data suggest the involvement of mechanosensitive Piezo1 channels capable of maintaining high-frequency spiking activity and of nociceptive TRPV1 channels in trigeminal headache pain responses after experimental ischemic stroke in mice.
中风后可能会立即出现严重头痛。由于头痛是由三叉神经脑膜传入纤维的激活引起的，我们评估了皮质光血栓形成后小鼠脑膜传入纤维活性的变化。皮质光血栓形成导致同侧大小不等的病变，与对侧感觉运动障碍有关。机械敏感 Piezo1 通道的激动剂 Yoda1 激活的机械敏感 Piezo1 通道的伤害性放电在缺血半球的脑膜传入纤维中增加。这些脑膜传入纤维在基线和 Yoda1 激活机械敏感 Piezo1 通道期间也具有更高的最大尖峰频率。此外，在这些脑膜传入纤维中，伤害性放电在辣椒素诱导瞬时受体电位香草素 1（TRPV1）通道的整个过程中都是活跃的。在同一组小鼠的对侧颅骨或对照小鼠中没有观察到这种激活。我们的数据表明，机械敏感 Piezo1 通道能够维持高频尖峰活动，以及伤害性 TRPV1 通道，在实验性缺血性中风后小鼠的三叉神经头痛疼痛反应中起作用。
