Abstract
Nociceptive sensitization is a conserved form of neuronal plasticity that serves an important survival function, as it fosters behavior that protects damaged tissue during healing. This sensitization may involve a lowering of the nociceptive threshold (allodynia) or an increased response to normally noxious stimuli (hyperalgesia). Although nociceptive sensitization has been intensively studied in vertebrate models, an open question in the field is the extent to which allodynia and hyperalgesia, which almost always occur in tandem, are truly separate events at the mechanistic level. We recently introduced a genetically tractable model for damage-induced nociceptive sensitization in Drosophila larvae, and identified a conserved cytokine signaling module that mediates development of allodynia following UV irradiation. This pathway includes the Drosophila homolog of Tumor Necrosis Factor-alpha (TNFalpha), Eiger, which is released from damaged epidermal cells and acts directly on its receptor, Wengen, located on nociceptive sensory neurons. Here we show that although Eiger and Wengen are both required for the development of thermal allodynia, they are dispensable for thermal hyperalgesia, suggesting, contrary to what is commonly assumed, that these two forms of hypersensitivity are initiated by separate genetic pathways.