A gene essential to the production of pain-sensing neurons in humans has been identified by an international team of researchers co-led by the University of Cambridge. The discovery, reported in the journal Nature Genetics, could have implications for the development of new methods of pain relief.
“The ability to sense pain is essential to our self-preservation, yet we understand far more about excessive pain than we do about lack of pain perception.”
– Geoff Woods
Pain perception is an evolutionarily-conserved warning mechanism that alerts us to dangers in the environment and to potential tissue damage. However, rare individuals – around one in a million people in the UK – are born unable to feel pain. These people accumulate numerous self-inflicted injuries, often leading to reduced lifespan.
Using detailed genome mapping, two teams of researchers collaborated to analyse the genetic make-up of 11 families across Europe and Asia affected by an inherited condition known as congenital insensitivity to pain (CIP). This enabled them to pinpoint the cause of the condition to variants of the gene PRDM12. Family members affected by CIP carried two copies of the variant; however, if they had only inherited one copy from their parents, they were unaffected.
The team looked at nerve biopsies taken from the patients to see what had gone wrong and found that particular pain-sensing neurons were absent. From these clinical features of the disease, the team predicted that there would be a block to the production of pain-sensing neurons during the development of the embryo – they confirmed this using a combination of studies in mouse and frog models, and in human induced pluripotent stem cells (skin cells that had been reset to their ‘master state’, which enables them to develop into almost any type of cell in the body).