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Papers of the Week

Papers: 25 May 2024 - 31 May 2024

2024 May 28

Nat Immunol


Editor's Pick

Nociceptor-immune interactomes reveal insult-specific immune signatures of pain.


Jain A, Gyori BM, Hakim S, Jain A, Sun L, Petrova V, Bhuiyan SA, Zhen S, Wang Q, Kawaguchi R, Bunga S, Taub DG, Ruiz-Cantero MC, Tong-Li C, Andrews N, Kotoda M, Renthal W, Sorger PK, Woolf CJ


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.