Axonal Mechanical Sensitivity in Neuritis

描述(由申请人提供)：慢性疼痛综合征，具有不明确的辐射性疼痛，在工业化国家的人口中有超过1/2的人在生活中的某个阶段受到折磨，可能是由于神经炎症或神经炎。在拟议的实验中，神经炎对感觉神经轴突的影响将使用单一的神经元记录模型来表征。初步研究结果表明，神经炎导致炎症部位的一群完整的伤害性感受器轴突变得机械敏感。在具体目标1中，我们将确定诱导机械感度的时间进程。我们的神经炎模型的特点是巨噬细胞和T淋巴细胞聚集。在特定目标2中，我们将使用特定的免疫组织化学标记物来确定这些免疫细胞出现和消失的时间进程。我们将把这与轴突机械敏感性的时间进程进行比较。轴突受损后发生的过程称为沃勒变性。这一过程导致巨噬细胞在神经膜内聚集，并激活雪旺细胞，以清除死亡的外周轴突产生的碎片。在特定的目标3中，我们将检验沃勒变性导致邻近的、否则完整的轴突的轴突机械敏感性的假设。这些实验有望增加我们对与神经炎和神经损伤相关的慢性疼痛机制的了解。

DESCRIPTION (provided by applicant): Chronic pain syndromes with poorly defined radiating pain afflict more than 1/2 of the population of industrialized countries at some point of their lives and may be due to nerve inflammation, or neuritis. In the proposed experiments, the effects of neuritis on sensory axons will be characterized using a single neuron-recording model. Preliminary findings showed that neuritis causes a subpopulation of intact nociceptor axons to become mechanically sensitive, at the site of inflammation. In Specific Aim 1, we will determine the time course of the induced mechanical sensitivity. Our model of neuritis is characterized by aggregation of macrophages and T-lymphocytes. In Specific Aim 2, we will determine the time course of the appearance and disappearance of these immune cells, using specific immunohistochemical markers. We will compare this to the time course of the axonal mechanical sensitivity. The process that occurs following axonal damage is called Wallerian degeneration. This process results in aggregation of macrophages within the perineurium and activation of Schwann cells to clear the debris produced by the dead peripheral axons. In Specific Aim 3, we will test the hypothesis that Wallerian degeneration causes axonal mechanical sensitivity in neighboring, otherwise intact axons. These experiments promise to increase our knowledge of the mechanisms of chronic pain related to neuritis and nerve injury.