System-wide protein profiling along the mouse pain-axis during neuropathic pain by Data Independent Acquisition Mass Spectrometry (DIA-MS)

慢性疼痛是一种复杂的适应性不良疾病，是由参与处理疼痛刺激（痛轴）的神经系统不同组织发生的分子变化引起的。然而，沿着疼痛轴的蛋白质网络的相关全系统改变目前在很大程度上是未知的。本提案的主要目的是利用新兴的数据独立获取质谱法（DIA-MS）发现和验证在神经性疼痛小鼠模型中疼痛轴的七个不同组织中发生的显著蛋白质变化。我们的初步工作证明了DIA-MS在以前所未有的深度、可重复性和敏感性发现小鼠疼痛性神经病变的新蛋白质特征方面的潜力。我们期望在这里提出的工作计划，以显著提高我们对神经性疼痛条件的理解，对疼痛管理具有潜在的深远影响。

Chronic Pain is a complex maladaptive disease that results from molecular changes occurring in different tissues of the nervous system involved in processing painful stimuli (pain-axis). However, associated system-wide alterations in protein networks along the pain-axis are currently largely unknown.The main aim of this proposal is to discover and validate significant protein changes occurring in seven different tissues of this pain-axis in a mouse model of neuropathic pain using emerging Data Independent Acquisition Mass Spectrometry (DIA-MS). Our preliminary work serves as a proof-of-principle of the potential of DIA-MS for discovering novel protein signatures of painful neuropathies in mice with unprecedented depth, reproducibility and sensitivity. We expect the here-proposed work program to significantly advance our understanding of neuropathic painful conditions with potentially far-reaching implications in pain management.