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New pain sensitivity gene identified

1 June 2015
Appeared in BioNews 804

Scientists studying people who are unable to feel pain have found a gene responsible for this rare condition, a finding they say could lead to new pain-relieving drugs.

People with two mutant copies of the PRDM12 gene experience a condition called congenital insensitivity to pain (CIP). The mutant gene appears to prevent nerve-sensing cells from developing properly.

'We are very hopeful that this new gene could be an excellent candidate for drug development,' said Dr Ya-Chun Chen from the University of Cambridge, the first author of the study published in Nature Genetics. '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.'

People with CIP do not notice when their bodies are damaged, meaning they accumulate injuries over time, which can be severe. For example, they might frequently bite their tongues and the insides of their mouths, or burn themselves because they cannot tell whether a surface is dangerously hot.

The researchers studied 11 families with members affected by CIP. Some had genes that had already been identified as being associated with the condition, but they also found ten new mutations in PRDM12 gene. The gene was already known to be involved in the modification of histones, which are able to switch other genes on and off - an epigenetic effect.

By studying mouse and frog embryos as well as human stem cells, they confirmed that the PRDM12 gene is normally switched on during the development of pain-sensing nerve cells. Taking small nerve samples these patients' feet, the researchers found that a severe loss of the nerve fibres that normally carry pain signals. The researchers believe that the mutant versions of the PRDM12 gene fail to switch on the genes responsible for the development of pain-sensing nerve fibres in people with CIP.

Epigenetic effects have been linked to pain sensitivity (see BioNews 741) and possibilities for using these mechanisms as a basis for treatments of pain are already being investigated . Two other genes linked to CIP are already being used to develop drugs currently being tested as painkillers. PRDM12 is the fifth gene that has been connected to CIP.

'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,' said Professor Geoff Woods of the University of Cambridge, one of the leaders of the research. '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.'

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