In constant pain? Blame your genes

KING’S COLLEGE LONDON (UK) — People who are more sensitive to pain may have a particular set of genes working against them, new research suggests.

Scientists have identified genes that interact with one another to regulate pain in humans, and found that differences in these genes may influence people’s sensitivity to pain. The findings add to a growing body of evidence that particular genes are involved in chronic pain and highlights this pathway as a potential target for more effective pain relief treatments for patients.

For the study, published in the journal PLOS ONE, researchers used a new method to study and compare DNA, called exome sequencing, to identify genetic variations relating to pain sensitivity.


“Chronic pain is a significant personal and socio-economic burden, with nearly one in five people experiencing it at some time in their lives,” says lead author Frances Williams, senior lecturer from the Department of Twin Research and Genetic Epidemiology at King’s College London.

“Current pain treatments often have either limited efficacy or side effects for many, so the possibility of a new approach to pain relief is an exciting development. The findings of our study contribute to the steps required to identify new treatments. In addition, we have shown that the exome sequencing method could be used to find important pathways in other common conditions.”

It is known that people who are most sensitive to pain encountered in everyday life are more likely to go on to develop chronic pain. To identify sensitivity levels, researchers tested 2,500 volunteers using a heating probe on the arm. Volunteers were asked to press a button when the heat became painful for them, which allowed the scientists to determine individuals’ pain thresholds.  Exome sequencing was then used to analyze the DNA of 200 of the most pain sensitive and 200 of the least pain sensitive people.

The results showed different patterns of genetic variants in each group—the pain sensitive people had less variation in their DNA than those who were pain insensitive. Serena Scollen, a geneticist at Pfizer Ltd. and co-author on the work, says: “Further studies are needed to understand fully the genetics that underlie pain sensitivity in humans, but early studies in this area are promising.”

Analyzing the networks linking the genes most influenced by genetic variation revealed the Angiontensin II pathways. The Angiotensin II protein has already been implicated in both animal models and human studies of pain but this is the first time the pathway has been shown to play a role using a genomic approach.

The findings provide evidence that this pathway may reveal novel targets for the treatment of pain. The study also showed how exome sequencing in normal individuals can provide insight into genetic processes and helps achieve greater understanding of common, yet complex, traits.

“This study is important because it extends the potential uses of human genetic sequencing to identify novel mechanisms of disease,” says co-author Steve McMahon, professor from King’s and head of the London Pain Consortium.

“Furthermore, the results specifically suggest that receptors for Angiotensin II might be important regulators of pain. It was also separately reported last month that pharmacological blockade of Angiotensin II receptors has been shown effective in treating neuropathic pain arising after herpes infection which, if substantiated, would support the value of these genetic studies.”

Source: King’s College London