Piezo2 Mediates Low-Threshold Mechanically Evoked Pain in the Cornea
Piezo2 Mediates Low-Threshold Mechanically Evoked Pain in the Cornea
复制标题
DOI：
10.1523/jneurosci.0247-20.2020
复制
发表时间：
2020-11-18
影响因子：
5.3
通讯作者：
Gomis, Ana
中科院分区：
文献类型：
--
作者：
Fernandez-Trillo, Jorge;Florez-Paz, Danny;Gomis, Ana
哺乳动物的Piezo2通道是本体感受器和皮肤触摸感受器传递无害机械力所必需的。相比之下，在Piezo2基因缺陷的小鼠中，引起疼痛的体感伤害性感受器神经元的机械反应保持完好或仅部分减弱。在眼角膜中，由多模式和纯机械感觉三叉神经节神经元检测到的机械力相对较低。它们的激活总是引起眼睛的不适或疼痛和保护性反射，因此是研究这类特殊伤害性神经元的机械转导机制的独特模型。培养的雄性和雌性小鼠机械和多模式伤害性感受器角膜神经元表现出快速、中等和缓慢地适应机械激活电流。对仅对机械力反应(纯机械性伤害性感受器)或同时显示TRPV1(瞬时受体电位阳离子通道V亚家族成员1)免疫反应性(多模式伤害性感受器)的角膜神经元的胞体和外周轴突的免疫染色显示，它们表达Piezo2。在感觉特异性Piezo2缺陷小鼠中，显示三种类型的机械诱发电流的角膜神经元的分布与野生型相似，但快速适应神经元、中等适应神经元和缓慢适应神经元的比例显著降低。对Piezo2条件性基因敲除小鼠角膜表面机械性和多模式伤害性感受器神经末梢的记录显示，机械刺激下机械敏感型神经末梢数量减少，神经末梢脉冲放电频率降低。与野生型相比，Piezo2基因缺陷小鼠角膜上涂有von Frey纤维引起的眨眼次数更少。总之，我们的结果提供了直接证据，证明Piezo2通道在角膜三叉神经细胞中支持不同动力学的机械激活电流，并有助于角膜伤害性感受器传递机械力。
Mammalian Piezo2 channels are essential for transduction of innocuous mechanical forces by proprioceptors and cutaneous touch receptors. In contrast, mechanical responses of somatosensory nociceptor neurons evoking pain, remain intact or are only partially reduced in Piezo2-deficient mice. In the eye cornea, comparatively low mechanical forces are detected by polymodal and pure mecha-nosensory trigeminal ganglion neurons. Their activation always evokes ocular discomfort or pain and protective reflexes, thus being a unique model to study mechanotransduction mechanisms in this particular class of nociceptive neurons. Cultured male and female mouse mechanoand polymodal nociceptor corneal neurons display rapidly, intermediately and slowly adapting mechanically activated currents. Immunostaining of the somas and peripheral axons of corneal neurons responding only to mechanical force (pure mechano-nociceptor) or also exhibiting TRPV1 (transient receptor potential cation channel subfamily V member 1) immunoreactivity (polymodal nociceptor) revealed that they express Piezo2. In sensory-specific Piezo2-deficient mice, the distribution of corneal neurons displaying the three types of mechanically evoked currents is similar to the wild type; however, the proportions of rapidly adapting neurons, and of intermediately and slowly adapting neurons were significantly reduced. Recordings of mechanoand polymodal-nociceptor nerve terminals in the corneal surface of Piezo2 conditional knock-out mice revealed a reduced number of mechano-sensitive terminals and lower frequency of nerve terminal impulse discharges under mechanical stimulation. Eye blinks evoked by von Frey filaments applied on the cornea were lower in Piezo2-deficient mice compared with wild type. Together, our results provide direct evidence that Piezo2 channels support mechanically activated currents of different kinetics in corneal trigeminal neurons and contributes to transduction of mechanical forces by corneal nociceptors.