Fruitfly study leads to human pain gene discovery

WASHINGTON - Researchers at Children’s Hospital Boston have reported the find of a novel pain gene.

People with minor variations in this gene showed clear differences in susceptibility to acute heat pain and chronic back pain.

The discovery, uncovered in a genome-wide hunt for pain genes in fruit flies, will lead to the development of new analgesics, the identification of risk factors for chronic pain and improved decision-making about the suitability of surgical treatment for different patients, according to Clifford Woolf, director of the F.M. Kirby Center and Program in Neurobiology at Children’s.

Nearly 12,000 genes were targeted for mutations specifically in nerve cells, using RNA interference (RNAi) technology.

The team then exposed the different mutant flies to noxious heat, and identified the ones that failed to fly away - and zeroed in on those with mutations that appeared to be specific to pain.

They found that a member of the family of calcium channels should be studied further. Other studies with mice demonstrated that this gene controls sensitivity to noxious heat in mammals as well as flies.

Further, functional MRI imaging revealed that it controls the processing of thermal pain signals in the brain: the heat pain signal seems to arrive appropriately at the thalamus, an early processing center, but does not travel to higher order pain centers in the cortex.

Together with colleagues at the University of Pittsburgh and the University of North Carolina, the team looked at four single nucleotide polymorphisms (SNPs), and found that certain less common SNPs were associated with reduced sensitivity to acute pain in a test administering a quick series of noxious heat pulses.

The international team plans further studies on the other pain genes identified in the fly screen.

“We are trying now to use a panel of the pain genes we’ve found- a2d3, KCNS1, GCH1 and others-to develop a genetic risk profile and then say, if you combine these polymorphisms you have a 60percent chance of chronic pain after surgery, versus say, if you have another polymorphism mix, a 5 percent chance,” Woolf said.

“This is another way to personalize medicine.”

The find is published in the November 12th issue of Cell. (ANI)