A team of scientists led by King’s College London has identified a particular set of 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 study, published today in PLoS Genetics, adds 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.
The collaborative study between King’s, Pfizer Ltd and the Beijing Genomics Institute, used a new method to study and compare DNA, called exome sequencing, to identify genetic variations relating to pain sensitivity.
Frances Williams, Senior Lecturer from the Department of Twin Research and Genetic Epidemiology at King’s College London, and lead author, said: ‘Chronic pain is a significant personal and socio-economic burden, with nearly one in five people experiencing it at some time in their lives. 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 analyse 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, Geneticist from Pfizer and co-author on the work said: ‘Further studies are needed to understand fully the genetics that underlie pain sensitivity in humans, but early studies in this area are promising.’
Analysing 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 finding provides 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.
Steve McMahon, co-author from King’s and head of the London Pain Consortium, said: ‘This study is important because it extends the potential uses of human genetic sequencing to identify novel mechanisms of disease. 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.’
Ruth McKernan, Chief Scientific Officer of Pfizer’s Research Unit in Cambridge that works on new pain drugs said: ‘This study demonstrates the value of collaborative efforts between academia and industry. The genetic influence on normal pain processing in human volunteer populations will add to other approaches and help us prioritise potential new mechanisms for treating pain. ’
