Axonal Mechanical Sensitivity in Neuritis

点击翻译按钮获取中文摘要

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.