Injury-induced nociceptive sensitization in adult D. melanogaster - Project Summary
Normal pain promotes health by warning us of potential tissue damage, but abnormal pain reduces the quality
of life for millions around the world. Pain sensitization after injury also promotes health by reducing re-injury
during healing. Some types of abnormal pain, including chronic pain, result from dysregulation of the pain
sensitization system. Available treatment for chronic pain is inadequate, in part because the deleterious side
effects of our best analgesics, the opioids, are made more hazardous by longer use. Better treatments for
abnormal pain are badly needed. We propose to reveal novel targets for pain medications by exploiting the
powerful genetic toolkit of the Drosophila model. When the fruit fly is injured by a controlled dose of ultraviolet
(UV) radiation, the animal exhibits allodynia, a manifestation of nociceptive sensitization. This means that the
injured animal will react with a nocifensive avoidance behavior in the form of an avoidance 'jump', in response
to a thermal stimulus with a reduced delay, compared with uninjured animals. This injury induced sensitization
paradigm has previously been used in larval flies to demonstrate that the nociceptor neuron requires signaling
by the Bone Morphogenetic Proteins (BMP) pathway to produce allodynia. BMP signaling components in the
fly are very similar to their mammalian orthologs. However, studies on larval flies are limited to the short time
available before the larva pupariates, becoming insensitive while metamorphosis reorganizes the larval tissues
to produce an adult. This project seeks to establish similar methods that can be applied to adult flies, which
live for 35 or more days, a much longer time window for studying processes like chronic pain. Preliminary
results indicate that UV-injured adults, like larvae, do indeed become hypersensitive to noxious stimuli. We are
now ready to map out the time required for injured adults to become sensitized and then return to normal
sensitivity, so that we can test the roles of genes that my serve to prolong pain sensitization, while others may
shorten the hypersensitive period. The roles of sex and aging in pain sensitization will also be examined.
Because of the high degree of functional conservation between fly and mammalian genes, components
identified by these experiments may represent targets for novel medications for the treatment of abnormal pain
in humans.
