A genetic cause of a rare inherited condition that leaves people with an inability to feel physical pain has been discovered by scientists.
About one in a million people are thought to be born without a sense of pain, which results in severe self-inflicted injuries from an early age and can lead to premature death.
Scientists studying the condition, known as congenital insensitivity to pain, in 11 affected families in Europe and Asia have now identified mutations in a gene called PRDM12 that was already known to be involved in activating genetic switches.
The researchers found that mutations in both copies of the gene that a person inherits from their mother and father – who are unaffected carriers of the defective gene – results in all the pain sensors of the body being turned off from birth.
Teenager Ashlyn Blocker, who lives with her parents in the US town of Patterson, Georgia, feels no pain and is one of a small number of people in the world who have been diagnosed with congenital insensitivity to pain.
“Everyone in my class asks me about it, and I say, ‘I can feel pressure, but I can’t feel pain’,” Ashlyn explained.
She cannot feel hot objects, or cuts and scratches on her skin, or insect bites. She can, and has, put her hand in boiling water without feeling any painful sensation – which has led to a lifetime of anxiety for her parents Tara and John.
“John and I had never heard of this condition. It was mind-boggling. It was so frightening,” Ms Blocker told the New York Times in 2012 after Ashlyn had undergone genetic tests to determine the cause of her condition.
The tests revealed that Ashlyn had inherited two defective copies of the SCN9A gene, which is known to be involved in the transmission of nerve impulses in pain-sensing neurones.
Congenital insensitivity to pain is such a rare condition that only about 20 cases have been reported in the scientific literature. Many of these are the result of mutations in other genes, including one called SCN9A, which is involved in the transmission of electrical signals in the nerves.
The PRDM12 gene, however, plays a key role in modifying a protein called chromatin which becomes attached to the DNA of the chromosomes and acts as a control switch to activate or deactivate other genes on the chromosome.
Researchers showed in a study published in the journal Nature Genetics that all the different PRDM12 mutations that they found in the 11 unrelated families resulted in the complete blocking of the gene.
As chromatin plays a particularly significant role in the formation of nerve cells, the findings could explain why pain-sensing neurons do not form properly in patients suffering from congenital insensitivity to pain, they said.
“The ability to sense pain is essential to our self-preservation, yet we understand far more about excessive pain that we do about lack of pain perception,” said Professor Geoffrey Woods from the Cambridge Institute for Medical Research at Cambridge University.
“Both are equally important to the development of new pain treatments. If we know the mechanisms that underlie pain sensation, we can then potentially control and reduce unnecessary pain,” Professor Woods said.
Babies who are born with CIP often damage themselves unintentionally by chewing their tongues, cheeks or hands. In later life, sufferers have to take precautions against bruising and being burned by hot objects – although sufferers can often distinguish between warm and cold they do not feel the painful stimulus of heat.
A handful of genes have been implicated in contributing to the risk of inheriting the condition. The SCN9A gene, for instance, provides the genetic instructions to make one part of the “sodium channel” protein involved in transmitting nerve impulses to the brain and spinal cord via pain neurons called nociceptors.
By understanding the causes of the lack of sensitivity to pain in such patients, scientists hope to better understand the nature of pain and how to combat it in patients who suffer from long-term, chronic pain.
“We are very hopeful that this new gene could be an excellent candidate for drug development, particularly given recent successes with drugs targeting chromatin regulators in human disease,” said Ya-Chun Chen from Cambridge University, the first author of the study.
“This could potentially benefit those who are at danger from lack of pain perception and help in the development of new treatments for pain relief,” Dr Chen said.Reuse content