This study investigates the immune mechanisms underlying inflammatory pain using single-cell transcriptomics in three mouse models of skin inflammation: zymosan injection, skin incision, and ultraviolet burn. The research reveals that immune cell infiltration and transcriptional changes closely correlate with the development and resolution of pain. Macrophages and neutrophils are identified as key players in pain development, with distinct transcriptional programs associated with each injury type. The study also identifies thrombospondin-1 (TSP-1), upregulated by immune cells, as a factor that inhibits nociceptor sensitization. The research highlights the importance of understanding the dynamic interplay between immune cells and sensory neurons in inflammatory pain. It shows that different immune responses are involved in distinct inflammatory pain conditions, and that the type of injury influences the immune response and the resulting pain. The study provides a comprehensive map of the neuroimmune landscape of inflammatory pain, revealing specific immune signatures associated with pain development and resolution. The findings suggest that TSP-1 plays a role in counteracting nociceptor sensitization by interacting with CD47 on DRG neurons, thereby reducing pain hypersensitivity. This study provides a framework for understanding the complex interactions between the immune system and sensory neurons in inflammatory pain, and highlights the potential of TSP-1 as a therapeutic target for pain management. The research also underscores the importance of identifying new neuroimmune targets to treat pain, particularly in the context of chronic inflammatory conditions.This study investigates the immune mechanisms underlying inflammatory pain using single-cell transcriptomics in three mouse models of skin inflammation: zymosan injection, skin incision, and ultraviolet burn. The research reveals that immune cell infiltration and transcriptional changes closely correlate with the development and resolution of pain. Macrophages and neutrophils are identified as key players in pain development, with distinct transcriptional programs associated with each injury type. The study also identifies thrombospondin-1 (TSP-1), upregulated by immune cells, as a factor that inhibits nociceptor sensitization. The research highlights the importance of understanding the dynamic interplay between immune cells and sensory neurons in inflammatory pain. It shows that different immune responses are involved in distinct inflammatory pain conditions, and that the type of injury influences the immune response and the resulting pain. The study provides a comprehensive map of the neuroimmune landscape of inflammatory pain, revealing specific immune signatures associated with pain development and resolution. The findings suggest that TSP-1 plays a role in counteracting nociceptor sensitization by interacting with CD47 on DRG neurons, thereby reducing pain hypersensitivity. This study provides a framework for understanding the complex interactions between the immune system and sensory neurons in inflammatory pain, and highlights the potential of TSP-1 as a therapeutic target for pain management. The research also underscores the importance of identifying new neuroimmune targets to treat pain, particularly in the context of chronic inflammatory conditions.