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Updated: Jun 25, 2025

Teasing Out the Interplay Between Natural Killer Cells and Nociceptor Neurons
Published on: June 30, 2022
Nociceptor-immune interactomes reveal insult-specific immune signatures of pain
Aakanksha Jain1, Benjamin M Gyori2,3,4, Sara Hakim1,5
1F. M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.
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.
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