Individuals who carry this gene are more susceptible to chronic pain following nerve injury.
Researchers at the Hebrew University of Jerusalem and elsewhere have succeeded in identifying for the first time a gene associated with susceptibility to chronic pain caused by nerve injury in humans – signaling a significant step toward better understanding and treating the condition.
Their findings were published online Aug 5 by Genome Research (see “Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2” ).
Human Susceptibility to Chronic Pain Varies Greatly
Chronic pain is a serious medical problem, afflicting approximately 20% of adults. Some individuals are more susceptible than others, and the degree of pain experienced after injury or surgery is known to be highly variable between patients, even under nearly identical circumstances.
The basis for this has remained largely unknown, prompting researchers to search for the contribution of genetics to chronic pain susceptibility. To accelerate research in this field, animal models are proving to be critical to understanding the underlying biology of chronic pain in human patients.
First, the international research team – led by Profs. Ariel Darvasi and Marshall Devor at The Hebrew University of Jerusalem and including scientists in Canada and Europe – 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. Next, they 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 then were able to confidently identify a single gene, CACNG2, as the likely candidate.
Tests Proved the Link to Chronic Pain in Animals
To further test the potential role for CACNG2 in chronic pain, the authors utilized a mouse strain harboring 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 CACNG2 in pain, even though it might be modest.
Significant Association with Chronic Pain in Humans
However, the question still remained as to whether the human version of the gene also is 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 will need to be analyzed further, the result is encouraging in pointing to this gene as a significant factor in experiencing pain.
“The immediate significance is the mere awareness that differences in pain perception may have a genetic predisposition,” Darvasi explained.
“Our discovery may provide insights for treating chronic pain through previously unthought-of mechanisms.”
In addition to the scientists from The Hebrew University, other contributors to the study were from the University of Toronto; Sanofi-Aventis, Germany; and the Karolinska Institute Center for Oral Biology, Sweden.
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
Source: The Hebrew University of Jerusalem, news release, Aug 5, 2010 (with modification)