美国哈佛医学院Clifford J. Woolf小组发现，痛觉感受器-免疫相互作用组揭示疼痛的特异性免疫特征。这一研究成果于2024年5月28日在线发表在国际学术期刊《自然—免疫学》上。

研究人员利用单细胞转录组学确定了三种小鼠皮肤炎症性疼痛模型中，与疼痛发展相关的免疫基因特征：酵母多糖素注射、皮肤切口和紫外线灼伤。研究人员发现巨噬细胞和中性粒细胞的招募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。

利用受体、配体、离子通道和代谢物介导的潜在相互作用的综合列表，生成损伤特异性神经免疫相互作用组，研究人员还发现免疫细胞在损伤后上调的血小板反应蛋白1抑制了痛觉感受器的敏化。这项研究为确定在不同疾病背景下调节疼痛的神经免疫轴奠定了基础。

据介绍，炎症性疼痛是由于痛觉感受神经元暴露于炎症介质，而导致敏感性增高和阈值降低所致。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充满挑战。

附：英文原文

Title: Nociceptor-immune interactomes reveal insult-specific immune signatures of pain

Author: Jain, Aakanksha, Gyori, Benjamin M., Hakim, Sara, Jain, Ashish, Sun, Liang, Petrova, Veselina, Bhuiyan, Shamsuddin A., Zhen, Shannon, Wang, Qing, Kawaguchi, Riki, Bunga, Samuel, Taub, Daniel G., Ruiz-Cantero, M. Carmen, Tong-Li, Candace, Andrews, Nicholas, Kotoda, Masakazu, Renthal, William, Sorger, Peter K., Woolf, Clifford J.

Issue&Volume: 2024-05-28

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.

DOI: 10.1038/s41590-024-01857-2

Source: https://www.nature.com/articles/s41590-024-01857-2