IU researchers have discovered a group of genes in both fruit flies and humans that plays a role in nerve sensitivity.
The study could help lead to new drug targets in pain management, according to an IU press release.
The research, published in the journal Cell Reports, was led by W. Daniel Tracey Jr., a professor in the College of Arts and Sciences’ Linda and Jack Gill Center for Biomolecular Science and the Department of Biology.
The authors on the paper are Ken Honjo of the University of Tsukuba in Japan and Stephanie E. Mauthner, an assistant scientist at IU.
A total of 36 genes were identified as having a role in either hypersensitivity or lack of sensation to stimuli, 20 of which are found in both humans and fruit flies. About 70 percent of genes in humans are also found in flies, originating in a common ancestor.
The 36 “genes of interest” in the study were screened from a total of 275 genes previously identified by Tracey’s lab to express at higher-than-average levels in nociceptors, the nerves that send signals to the brain in response to strong external stimuli, according to a press release.
The human brain can interpret signals from these nerves as pain. In flies, they might be triggered by mechanical stimuli or high heat. Of the 36 genes under investigation, 22 genes were found to play a role in hypersensitivity to heat. Fourteen were found to play a role in insensitivity.
“This first group appears to activate a function that inhibits the nociceptors,” Tracey said in a press release. “These are interesting because you can imagine that if you could make a drug that was able to activate an inhibitor, then you could block pain.”
As the first researchers to assign a function to the majority of these genes, Tracey’s team had the right to name them. The genes associated in heat hypersensitivity were named after objects that burn at high temperatures, including “black match,” “eucalyptus,” “firelighter,” “prima cord.”, “jet fuel,” “detonator,” “gasoline,” “smoke alarm” and “jetboil,” according to a press release.
To identify these genes, Tracey’s team bred multiple strains of fruit flies, each with one of the 275 genes under investigation suppressed through RNA interference in which RNA molecules are used to inhibit the expression of a specific gene. The flies were then exposed to two temperatures 42 and 46 degrees Celsius as larvae, which normally react to the higher of these temperatures by rolling slowly. If they rolled more quickly at 42 degrees, it indicated hypersensitivity. If they did not roll at 46 degrees, it indicated insensitivity, according to a press release.
Moreover, Tracey said nine of the genes related to insensitivity caused the flies to grow a lower-than-average number of the nerve branches, or “dendrites,” connecting nociceptors to the surface of the body. Two of the genes related to hypersensitivity, including “smoke alarm,” caused the flies to grow extra dendrites, according to a press release.
Tracey’s goals are to conduct additional studies that study the exact chemical pathways these genes activate in nerve cells in order to understand why they result in changes in sensitivity.
Leo Smith
