Hebrew U. team fights against pain

Chronic problem that afflicts one in five adults.

Pain 311 (photo credit: Courtesy)
Pain 311
(photo credit: Courtesy)
For the first time, a human gene connected to susceptibility to chronic pain caused by nerve injury has been identified.
The accomplishment belongs to Hebrew University of Jerusalem researchers, along with colleagues abroad, who say it constitutes a significant step toward better understanding and treating the condition.
Chronic pain is a serious medical problem, afflicting about one-fifth of all adults.
Some people are more susceptible to it than others, and the degree of pain experienced after injury or surgery is highly variable; some may feel a lot of pain and others less, even if they were injured under nearly identical circumstances.
Because of this variability, researchers have been looking at the influence of genetics on susceptibility to chronic pain.
Prof. Ariel Darvasi of HU’s Alexander Silberman Institute of Life Sciences published an article in the August 5 issue of the journal Genome Research about a region of mouse chromosome #15 that apparently contains a genetic variant or variants contributing to pain. However, as this region contains many genes, the responsible variant remained unknown until now.
Darvasi and an international team of researchers – including HU pain researcher Prof. Marshall Devor and scientists from the University of Toronto, the Sanofi-Aventis pharmaceutical company in Germany, and the Karolinska Institute Center for Oral Biology in Sweden – undertook two fine-mapping approaches to narrow down the chromosomal locus to an interval of 155 genes. By applying a bioinformatics approach and whole genome microarray analysis, they were able to confidently identify a single gene, Cacgn2, as the likely candidate.
To further test the potential role of Cacgn2 in chronic pain, the authors used a mouse strain bearing a mutant version of the gene that had previously been used in epilepsy research. In testing the mice for behavioral and electrophysiological characteristics of chronic pain, they found that the observations were consistent with a functional role for Cacgn2 in pain, even though it might be “modest.”
However, the question still remained as to whether the human version of the gene was also important for chronic pain. Analyzing a cohort of breast cancer patients who experienced chronic pain half a year or more after they had undergone removal or partial removal of a breast, they found that genetic variants of Cacng2 were significantly associated with this chronic pain.
The authors cautioned that although this association would need to be analyzed further, the result was encouraging.
Darvasi noted that the immediate significance was “the mere awareness that differences in pain perception may have a genetic predisposition.”