Identification of the peptide Vulnusin, a wound signal that mediates mechanical-injury-induced nociception in Drosophila

Animals can acutely sense a puncture or cut in their skin through nociceptors. However, the molecular identity of such "wound signals" and their receptors on nociceptors remains unknown. In Drosophila larvae, class IV dendritic arborization neurons are multimodal nociceptors that detect harsh touch, heat, and UV light to initiate nociceptive behavior. Here, we identify Vulnusin (from vulnus, a Latin word for wound), an endogenous peptide likely serving as a wound signal. Vulnusin, derived from the larval epidermis, activates PPK1/PPK26 ion channels expressed endogenously on nociceptors and heterologously in Drosophila S2 cells. Moreover, Vulnusin acts together with PPK1/PPK26 to trigger puncture-induced rolling behavior, a response to mechanical injury. These findings establish Vulnusin as a ligand that activates larval nociceptors and mediates mechanical-injury-induced nociception.