(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
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
highly variable; some may feel a lot of pain and others less, even if
injured under nearly identical circumstances.
Because of this
variability, researchers have been looking at the influence of genetics
susceptibility to chronic pain.
Prof. Ariel Darvasi of HU’s Alexander
Silberman Institute of Life Sciences published an article in the August 5
of the journal Genome Research
about a region of mouse chromosome #15
apparently contains a genetic variant or variants contributing to pain.
as this region contains many genes, the responsible variant remained
Darvasi and an international team of researchers – including
HU pain researcher Prof. Marshall Devor and scientists from the
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
155 genes. By applying a bioinformatics approach and whole genome
analysis, they were able to confidently identify a single gene, Cacgn2,
To further test the potential role of Cacgn2 in chronic
pain, the authors used a mouse strain bearing a mutant version of the
had previously been used in epilepsy research. In testing the mice for
behavioral and electrophysiological characteristics of chronic pain,
that the observations were consistent with a functional role for Cacgn2
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
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
they found that genetic variants of Cacng2 were significantly associated
this chronic pain.
The authors cautioned that although this association
would need to be analyzed further, the result was encouraging.
noted that the immediate significance was “the mere awareness that
in pain perception may have a genetic predisposition.”