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The Gene at the Heart of Pain

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Thursday, September 9th, 2010

As reported in Israel 21C: A gene affecting chronic pain caused by nerve injury has been identified by Israeli and international researchers, opening the way for new treatment approaches.

A gene associated with susceptibility to chronic pain caused by nerve injury in humans has been identified by a team of Israeli and international researchers, offering hope of new treatments for sufferers everywhere.

Chronic pain affects about 20 percent of adults worldwide, and can range from persistent headaches, to back pain, the pain of arthritis, and even psychogenic pain, where doctors can’t find the cause for a constant pain.

While it is recognized that some people are more susceptible than others to chronic pain, no one knows why. Given the same injury and the same operation, people will suffer variable degrees of pain, even under nearly identical circumstances.

Now researchers at the Hebrew University of Jerusalem (HUJ), the University of Toronto in Canada, Sanofi-Aventis in Germany and the Karolinska Institute Center for Oral Biology in Sweden, believe they may have found the answer in genetics.

“The immediate significance is the mere awareness that differences in pain perception may have a genetic predisposition,” says Prof. Ariel Darvasi of the Alexander Silberman Institute of Life Sciences at the Hebrew University. “Our discovery may provide insights for treating chronic pain through previously unthought-of mechanisms.”

The gene at the heart of your pain perception

In a report published late last week in Genome Research, Darvasi and colleagues identified a region of mouse chromosome 15 that likely contained a genetic variant or variants contributing to pain. However, this region contains many genes, and the responsible variant remained unknown.

Darvasi and his team, which includes Prof. Marshall Devor of the Hebrew University, undertook two fine-mapping approaches to narrow down the chromosomal locus to an interval of 155 genes.

By applying bioinformatics approaches and whole genome microarray analysis, they were able to confidently identify a single gene, Cacgn2, as the likely candidate. In mouse experiments, the researchers were able to confirm that Cacfn2 has a functional role in pain.

To find out whether the human version of the gene also plays a part in chronic pain, the scientists then analyzed a group of breast cancer patients who experienced chronic pain more than six months after they had undergone removal or partial removal of a breast. The researchers found that genetic variants of Cacng2 were significantly associated with this chronic pain.

While cautioning that this association will need further analysis, the researchers say that the result suggests that this gene is an important factor in experiencing pain.

The work was supported by the Israel Science Foundation, the Hebrew University Center for Research on Pain, the Canada Research Chair Program and the European Community’s 6th Framework Program.