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Role of 'pain-free' gene explained

14 December 2015

By Jessica Richardson

Appeared in BioNews 832

Scientists have discovered why people with a rare genetic mutation are unable to feel pain – a finding that could lead to treatments for chronic pain conditions.

Researchers investigated the gene SCN9A, which encodes the sodium channel Nav1.7, which allows the transmission of pain signals to the brain. Individuals who are insensitive to pain carry a mutation in this gene, which renders Nav1.7 non-functional, but painkillers that block this channel have been surprisingly unsuccessful.

They found that deleting Nav1.7 caused an increase in the production of opioid peptides, the body’s natural painkillers, which means that people with this mutation naturally produce higher levels of these opioids.

When the team treated genetically modified mice that lacked a functional Nav1.7 with the opioid blocker naloxone – a drug normally used to treat drug addiction – and found that their pain sensitivity was restored. In the study, which was published in Nature Communications, they also gave naloxone to a 39-year-old woman with a SCN9A mutation and she was able to feel pain for the first time.

'After a decade of rather disappointing drug trials, we now have confirmation that Nav1.7 really is a key element in human pain,' said senior author Professor John Wood of University College London. 'The secret ingredient turned out to be good old-fashioned opioid peptides, and we have now filed a patent for combining low-dose opioids with Nav1.7 blockers. This should replicate the painlessness experienced by people with rare mutations, and we have already successfully tested this approach in unmodified mice.'

However, long-term use of opioid pain medications, which include morphine, can lead to addiction and tolerance. Further research is required to investigate any possible side effects of the drugs and identify conditions for which this treatment might be useful.

Dr Kenji Okuse from Imperial College London, who was not involved in the study, told New Scientist, 'Opioids and Nav1.7 blockers could provide much stronger analgesics, but they will not necessarily be better for patients. If we take the combination therapy route, people would have to take opioids throughout the lifetime, which is not a welcome thing.'

Professor Wood explained that this might not necessarily be a barrier to the treatment. 'Used in combination with Nav1.7 blockers, the dose of opioid needed to prevent pain is very low,' he said. 'People with non-functioning Nav1.7 produce low levels of opioids throughout their lives without developing tolerance or experiencing unpleasant side effects.' Professor Wood said he hoped to see human trials using this combination approach to treating chronic pain by 2017.

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