Modulation of spike generation in somatosensory endings of the cornea - the role of chloride currents in inflammatory sensitization

来自感觉末梢器官的传入信号甚至在到达脊髓之前就受到相当大的调制。感觉神经元可能会适应，它们可能会被敏化，甚至可能会被公开地打开或关闭。这种调节的分子过程吸引了大量的研究工作，但很少被详细破译。在哺乳动物的躯体感觉系统中，单个初级感觉神经元的反应特征可以被免疫系统显著改变。炎症介质使神经末梢敏感并增强刺激诱导的传入信号的强度。基于最近的外周炎性痛觉过敏的概念，我们研究的假设，这种敏化是促进去极化氯电流。探讨初级传入神经元的氯电流的影响，我们将分析在哺乳动物眼角膜的体感纤维。在两个平行和互补的方法中，我们将研究氯离子转运蛋白和氯离子通道在角膜轴突中的表达，同时，研究角膜神经末梢中与氯离子相关的尖峰生成方面。这两种方法旨在澄清两个问题：（1）哪种蛋白质设备介导躯体感觉神经末梢中的氯化物效应;（2）这些蛋白质如何参与炎症期间神经末梢的敏化？为了解决这些问题，我们结合联合收割机的蛋白质表达和蛋白质调节的研究，在炎症介质的存在下，神经末梢的敏感性的测定。这个项目将大大增加我们的理解可塑性的躯体感觉系统通过一种新的方法外周痛觉过敏。

Afferent signals arising from sensory end organs are subject to considerable modulation even before reaching the spinal cord. Sensory neurons may adapt, they may be sensitized, or may even be overtly switched on or off. The molecular processes underlying such regulation have attracted considerable research effort but have only rarely been deciphered in detail. In the somatosensory system of mammals, the response characteristics of individual primary sensory neurons can be altered dramatically by the immune system. Inflammatory mediators sensitize nerve terminals and boost the intensity of stimulus-induced afferent signals. Based on recent concepts of peripheral inflammatory hyperalgesia, we examine the hypothesis that such sensitization is promoted by depolarizing chloride currents.To explore the effects of chloride currents in primary afferent neurones, we will analyse somatosensory fibres in the cornea of the mammalian eye. In two parallel and complementary approaches, we will study the expression of chloride transporters and chloride channels in corneal axons and, at the same time, examine chloride-related aspects of spike generation in corneal nerve terminals. The two approaches are designed to clarify two questions: (1) Which protein equipment mediates chloride effects in somatosensory nerve terminals; and (2) how are these proteins involved in the sensitization of nerve terminals during inflammation? To address these questions we combine studies of protein expression and protein regulation with the determination of nerve terminal sensitivity in the presence of inflammatory mediators. This project will add considerably to our understanding of plasticity in the somatosensory system through a novel approach to peripheral hyperalgesia.