Axonal Mechanical Sensitivity in Neuritis

描述（由申请人提供）：在工业化国家，超过1/2的人口在其生命的某个阶段遭受慢性疼痛综合征，伴有不明确的放射性疼痛，可能是由于神经炎症或神经炎。在提出的实验中，神经炎对感觉轴突的影响将使用单个神经元记录模型进行表征。初步研究结果表明，神经炎导致完整的伤害感受器轴突亚群在炎症部位变得机械敏感。在具体目标1中，我们将确定诱导机械敏感性的时间过程。我们的神经炎模型以巨噬细胞和t淋巴细胞聚集为特征。在特异性靶2中，我们将使用特异性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过程。我们将其与轴突机械灵敏度的时间过程进行比较。轴突损伤后发生的过程称为沃勒氏变性。这一过程导致神经周围巨噬细胞聚集，激活雪旺细胞清除死亡外周轴突产生的碎片。在Specific Aim 3中，我们将验证沃勒氏变性导致相邻轴突机械敏感性的假设，否则是完整的轴突。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认识。

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.