Ouch! Pain threshold genes amplified by lifestyle - life - 04 February 2014 - New Scientist

If you flinch where others merely frown, you might want to take a look at your lifestyle. That's because environmental factors may have retuned your genes to make you more sensitive to pain.

"We know that stressful life events such as diet, smoking, drinking and exposure to pollution all have effects on your genes, but we didn't know if they specifically affected pain genes," says Tim Spector of King's College London.

Now, a study of identical twins suggests they do. It seems that epigenetic changes – environmentally triggered chemical alterations that affect how active your genes are – can dial your pain threshold up or down. This implies that genetic tweaks of this kind, such as the addition of one or more methyl groups to a gene, may account for some differences in how our senses operate.

Spector and his colleagues assessed the ability of hundreds of pairs of twins to withstand the heat of a laser on their skin, a standard pain test. They selected 25 pairs who showed the greatest difference in the highest temperature they could bear. Since identical twins have the same genes, any variation in pain sensitivity can be attributed to epigenetic differences.

Pain thermostat

The researchers screened the twins' DNA for differences in methylation levels across 10 million gene regions. They found a significant difference in nine genes, most of which then turned out to have been previously implicated in pain-sensitivity in animal experiments.

The greatest difference was seen in the promoter "switch" of the TRPA1 gene, which makes an ion channel on the surface of nerve cells that detect pain. "[TRPA1 is] like a thermostat, dictating how we perceive heat and turn that into pain," says Spector. An increase in methylation of around 10 per cent inTRPA1 equated roughly to feeling pain at 2 °C lower.

The team then repeated the experiment with 50 unrelated individuals. Sure enough, differences in pain sensitivity correlated with differences in methylation levels in the nine genes they'd identified with the twins.

Identification of epigenetically altered pain genes opens up ways to screen people for which painkiller might work best, and potentially identify new drugs, says Spector.

"Variation in pain sensitivity between individuals is a long-standing matter of debate, so regulation of gene activity by DNA methylation is one possibility to explain it," says Ingo Kurth, who studies pain mechanisms at the Jena University Hospital in Germany. "TRPA1 is a hot candidate as mutations in the gene have previously been associated with familial pain problems," he says.

Journal reference: Nature Communications, DOI: 10.1038/ncomms3978


http://www.newscientist.com/article/dn24998-ouch-pain-threshold-genes-amplified-by-lifestyle.html