PDF(Pubmed)
Abstract：
Inflammatory pain results from the heightened sensitivity and reduced threshold of nociceptor sensory neurons due to exposure to inflammatory mediators. However, the cellular and transcriptional diversity of immune cell and sensory neuron types makes it challenging to decipher the immune mechanisms underlying pain. Here we used single-cell transcriptomics to determine the immune gene signatures associated with pain development in three skin inflammatory pain models in mice: zymosan injection, skin incision and ultraviolet burn. We found that macrophage and neutrophil recruitment closely mirrored the kinetics of pain development and identified cell-type-specific transcriptional programs associated with pain and its resolution. Using a comprehensive list of potential interactions mediated by receptors, ligands, ion channels and metabolites to generate injury-specific neuroimmune interactomes, we also uncovered that thrombospondin-1 upregulated by immune cells upon injury inhibited nociceptor sensitization. This study lays the groundwork for identifying the neuroimmune axes that modulate pain in diverse disease contexts.
摘要：
炎性疼痛是由于暴露于炎性介质引起的伤害感受器感觉神经元的敏感性提高和阈值降低所致。然而,免疫细胞和感觉神经元类型的细胞和转录多样性使得破译疼痛背后的免疫机制具有挑战性。在这里，我们使用单细胞转录组学技术来确定与小鼠三种皮肤炎性疼痛模型中疼痛发展相关的免疫基因特征：酵母聚糖注射，皮肤切口和紫外线烧伤。我们发现巨噬细胞和中性粒细胞募集密切反映了疼痛发展的动力学，并确定了与疼痛及其解决相关的细胞类型特异性转录程序。使用受体介导的潜在相互作用的综合列表，配体，离子通道和代谢产物产生损伤特异性神经免疫相互作用，我们还发现，在损伤后免疫细胞上调的血小板反应蛋白-1抑制了伤害感受器的致敏作用。这项研究为确定在不同疾病环境中调节疼痛的神经免疫轴奠定了基础。
