Cytokine signaling mediates UV-induced nociceptive sensitization in Drosophila larvae.
BACKGROUND
Heightened nociceptive (pain) sensitivity is an adaptive response to tissue damage and serves to protect the site of injury. Multiple mediators of nociceptive sensitization have been identified in vertebrates, but the complexity of the vertebrate nervous system and tissue-repair responses has hindered identification of the precise roles of these factors.


RESULTS
Here we establish a new model of nociceptive sensitization in Drosophila larvae, in which UV-induced tissue damage alters an aversive withdrawal behavior. We find that UV-treated larvae develop both thermal hyperalgesia, manifested as an exaggerated response to noxious thermal stimuli, and thermal allodynia, a responsiveness to subthreshold thermal stimuli that are not normally perceived as noxious. Allodynia is dependent upon a tumor necrosis factor (TNF) homolog, Eiger, released from apoptotic epidermal cells, and the TNF receptor, Wengen, expressed on nociceptive sensory neurons.


CONCLUSIONS
These results demonstrate that cytokine-mediated nociceptive sensitization is conserved across animal phyla and set the stage for a sophisticated genetic dissection of the cellular and molecular alterations responsible for development of nociceptive sensitization in sensory neurons.
Department of Biochemistry and Molecular Biology, University of Texas Graduate School of Biomedical Sciences, USA.
Daniel T
DT
Babcock
Christian
C
Landry
Michael J
MJ
Galko
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D004330:Drosophila / Q000033:anatomy & histology / Q000502:physiology*; D004817:Epidermis / Q000473:pathology / Q000528:radiation effects; D006930:Hyperalgesia / Q000378:metabolism*; D007814:Larva / Q000033:anatomy & histology / Q000502:physiology* / Q000528:radiation effects; D009619:Nociceptors / Q000378:metabolism; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D017288:Pain Threshold; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014466:Ultraviolet Rays
D014409:Tumor Necrosis Factor-alpha; D020169:Caspases