Gene That Triggers Pain Relief Discovered

A newly discovered gene, which helps control the sense of pain, could give rise to future treatments for sufferers of chronic pain.

The gene is also linked to synaesthesia, a condition that leads to sensations of one kind being perceived as another. Words or numbers might be perceived as colors - the number seven as the color yellow - or colors could be heard as music.

Dr. Greg Neely a recently-appointed researcher at Sydney's Garvan Institute of Medical Research, led the project with Professor Josef Penninger, while at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences in Vienna. The research is published in the current issue of Cell.

The research team screened the genome of fruit flies to investigate pain perception - in particular, the insects' response to heat-induced pain.

After identifying 600 pain associated genes, the researchers honed in on one gene in particular, known as α2δ3, a gene shared with mice and people. The gene seemed to hold promise because it triggered the same cellular mechanisms as some existing painkillers.

American collaborators (at Harvard, Pittsburgh, and North Carolina Universities) then examined variations of the α2δ3 gene in people and found that one particular variation not only reduced sensitivity to acute pain, but also made patients much less likely to have chronic lower back pain.

After identifying 600 pain associated genes, the researchers honed in on one gene in particular, known as α2δ3, a gene shared with mice and people. The gene seemed to hold promise because it triggered the same cellular mechanisms as some existing painkillers.

American collaborators (at Harvard, Pittsburgh and North Carolina Universities) then examined variations of the α2δ3 gene in people and found that one particular variation not only reduced sensitivity to acute pain, but also made patients much less likely to have chronic lower back pain.

Using functional MRI scanners to look at the brains of mice with mutant α2δ3 genes revealed that the gene controls the way heat pain signals are processed in the brain.

In these mutant mice, the pain impulse arrives in the brain correctly at the thalamus, a first sensory processing centre, but are not properly sent on to the higher processing centers in the cortex, which normally alert the animals to the sensation of pain. The researchers found that areas in the brain responsible for experiencing sight, smell, and hearing were being activated instead.

"From a medical research perspective, our findings help explain the wide variance in how people experience pain," Dr Neely said, in a press release.

"Not only that, they indicate potential ways of treating acute and chronic pain in the future - by mimicking the effects of the mutated gene."

"From the perspective of a neuroscientist interested in how the brain works, our research was thrilling because it provided the first genetic insight into synaesthesia, or crossing of the senses, where people experience sounds or written words as colors, or experience tastes, smells and shapes in linked combinations."

"The mice we used, with the mutated gene, experienced heat as other perceptions, including vision, sound and smell. We could see their brains lighting up in those areas with MRI scanning."

"To see if this sensory cross activation, or synesthesia, was pain specific, we touched their whiskers. It appeared that they could hear, smell and see our touch."

"If you think of the neurons in the brain as wires with insulation, it's as if their sensory insulation had been stripped, and a trigger to one sensory input, like touch or heat, could be perceived as another."

"In these mice, a part of the brain often referred to as the 'pain matrix' didn't light up as much as normal because the pain signals were unable to spread to these higher structures in the brain."

"That suggests our new gene controls the transmission of signals to the parts of the brain that form our pain experience."

"Pain is, after all, a perceptual process, as much as our experience of the taste of chili."

"Composer Franz Liszt saw colors when hearing musical notes. Abstract artist Wassily Kandinsky saw colors when hearing music. What's to say we can't translate the experience of pain into the color blue or the sound of music?"

Source: Garvan Institute of Medical Research--What does the discovery mean for the future of pain medicine? Leave a comment.

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