Department of Medical Neurobiology, Institute for Medical Research Israel Canada, Faculty of Medicine, The Hebrew University, 9112001 Jerusalem, Israel; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, 9112001 Jerusalem, Israel.
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, Spain.
Neuron. 2019 May 22;102(4):801-812.e5. doi: 10.1016/j.neuron.2019.03.005. Epub 2019 Mar 26.
Nociceptive terminals possess the elements for detecting, transmitting, and modulating noxious signals, thus being pivotal for pain sensation. Despite this, a functional description of the transduction process by the terminals, in physiological conditions, has not been fully achieved. Here, we studied how nociceptive terminals in vivo convert noxious stimuli into propagating signals. By monitoring noxious-stimulus-induced Ca dynamics from mouse corneal terminals, we found that initiation of Na channel (Nav)-dependent propagating signals takes place away from the terminal and that the starting point for Nav-mediated propagation depends on Nav functional availability. Acute treatment with the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) resulted in a shift of the location of Nav involvement toward the terminal, thus increasing nociceptive excitability. Moreover, a shift of Nav involvement toward the terminal occurs in corneal hyperalgesia resulting from acute photokeratitis. This dynamic change in the location of Nav-mediated propagation initiation could underlie pathological pain hypersensitivity.
伤害性感受器末端具有检测、传递和调节有害信号的要素，因此是疼痛感觉的关键。尽管如此，伤害性感受器末端在生理条件下的转导过程的功能描述尚未完全实现。在这里，我们研究了伤害性感受器末端如何将有害刺激转化为传播信号。通过监测来自小鼠角膜末端的有害刺激诱导的 Ca 动力学，我们发现依赖 Nav 的传播信号的起始发生在末端之外，并且 Nav 介导的传播的起始点取决于 Nav 功能的可用性。急性给予促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素 1β（IL-1β）导致 Nav 参与的位置向末端转移，从而增加伤害性兴奋性。此外，急性光角膜炎引起的角膜痛觉过敏导致 Nav 参与的位置向末端转移。这种 Nav 介导的传播起始位置的动态变化可能是病理性疼痛过敏的基础。
