In Sensation on a Small Scale, PRF looks at how Drosophila and C. elegans are being used to study the biology of nociception. Here, we find out how some of that work got off the ground.
Fruit flies made their debut as model organisms for pain less than a decade ago. That was when W. Daniel Tracey, now a researcher at Duke University in Durham, North Carolina, published the finding that flies respond with a unique behavior to noxious heat, poking or pinching (Tracey et al., 2003).
Tracey says he first made that discovery while he was a graduate student in genetics at Stony Brook University in New York. One year, he tagged along with his wife (a neurobiology student) to her department retreat, and found himself sitting in on a seminar by Lorne Mendell on pain. “I started daydreaming and wondering if you could use flies to study pain, because I was thinking about what I wanted to do as a postdoc,” he told PRF. After the talk, he went straight back to the lab and did a little experiment. “I held a hot probe up to the larva and saw this really dramatic behavioral response. The larva twisted around its long body axis in a corkscrew motion,” Tracey recalled.
The gyrations were totally unlike anything he had seen before: “Normally the larva has a peristaltic muscle contraction that propels it along, like an inchworm,” Tracey explained.
When Tracey first saw the weird behavior, he had a predictable response: “Somebody must be studying this.” He looked through the literature but found nothing. “I only found things arguing that there’s no such thing as pain in insects,” he said.
With that, Tracey had hatched his plan for a postdoc. He wrote to several researchers, looking for someone who would let him hunt down genes involved in the nociceptive behavior. Seymour Benzer at the California Institute of Technology agreed, and Tracey was off to work in the lab of one of his greatest scientific heroes.
In Benzer’s lab, Tracey screened 1500 fly lines to find one mutant that lacked the writhing response to heat, and in that way identified the first fly nociception gene, which he named painless. Later, his lab at Duke identified the nociceptive neurons that express painless and mediate the nociceptive response, and showed that the larvae’s twisting behavior serves as a defense against stinging wasps (Hwang et al 2007 PMID 18060782). Recently, they dissected the role of another gene, pickpocket, in mechanical nociception (Zhong et al., 2010).
Now, Tracey says, his lab is taking up a global strategy for finding genes involved in fly nociception. They are using RNAi to knock out hundreds of different genes specifically in the nociceptor neurons.
