Pain Matters: Nociceptive signaling drives neural encoding of inflammatory responses

Pain is a cardinal sign of inflammation, constructed by the brain from peripheral nociceptive input. Yet, its role in the brain's response to inflammation remains unknown. Here, we demonstrate that nociceptive signaling is essential for the brain to represent and replay inflammatory states. Analysis of human fMRI and mouse activity mapping revealed that peripheral inflammation generates a distinct brain state. In mice, ablation of TRPV1+ sensory neurons or pharmacological analgesia disrupted this organization and prevented the insular cortex from forming retrievable immune representations. Conversely, augmenting nociceptive signaling during inflammation strengthened subsequent immune recall. These findings identify nociceptive input as a critical signal in brain-immune dialogue, enabling the encoding and retrieval of inflammatory events.