THE WOMEN WHO FELT PAIN FOR THE FIRST

A woman has felt pain for the first time aged 39, following an experiment that could lead to powerful new ways to treat painful conditions such as arthritis.

The woman was born with a genetic condition that means she cannot feel pain, but a drug normally used to treat drug overdoses enabled her to feel the pain of a laser beam on her skin – a sensation scientists say she quite enjoyed.

Only a handful of people around the world are born unable to feel pain. These individuals can often experience a range of injuries when they are young. Babies with the condition tend to chew their fingers, toes and lips until they bleed, and toddlers can sustain more knocks, tumbles and encounters with sharp or hot objects than normal. Many die at a young age.

The disorder is caused by a rare genetic mutation that results in a lack of ion channels that transport sodium across sensory nerves. Without these Nav1.7 channels, nerve cells cannot communicate pain. After this was discovered, researchers rushed to make compounds that blocked Nav1.7 channels, thinking they might be able to stop pain in people with a normal pain response. “It looked like a fantastic drug target,” says John Wood at University College London. “Pharma companies went bananas and made lots of drugs.” But while a few compounds had some success, none brought about the total absence of pain seen in people who lack the channel naturally.

To find out why, Wood and his colleagues studied genetically modified mice missing Nav1.7. These animals feel no pain either – they show no reaction when their tails are exposed to extreme hot or cold temperatures, for example.

A closer analysis of the rodents’ nerves showed that mice lacking Nav1.7 had a huge increase in the expression of genes responsible for opioid peptides, the body’s natural painkiller. The mice seem to be making more of these pain-relieving peptides, which might explain why people missing the channel also don’t feel pain.

If that were the case, figured Wood, a drug that stops opioid peptides working may reverse the disorder. Sure enough, when the team gave mice naloxone – which blocks opioid receptors and is used to treat overdoses of morphine and heroin – the animals could feel pain again.

What’s more, when the team gave the drug to their female volunteer the effect was the same. The woman, who wishes to stay anonymous, says she hopes that the drug could be used to treat any children she might have with the same condition.

Wood isn’t sure whether this will be an option, since long-term use of naloxone could have side effects. The opposite approach, however, may help to treat pain, he says. When his team gave normal mice Nav1.7 channel blockers together with opioid drugs, they managed to stop them feeling any pain (Nature Communications, doi.org/9sr).

The mice in this experiment felt as little pain as GM mice missing the Nav1.7 channel, says Wood. He has taken out a patent on the use of the two drugs for pain relief.

Kenji Okuse at Imperial College London believes the findings may change the way doctors think about treating pain conditions, but need further examination. “Opioids and Nav1.7 blockers could provide much stronger analgesics, but they will not necessarily be better for patients,” he says. “If we take the combination therapy route, people would have to take opioids throughout the lifetime, which is not a welcome thing.”

By Jessica Hamzelou in "New Scientist" USA, vol.228,n. 3051, December 12 - 18, 2015, excerpt p. 11, Digitized, adapted and illustrated to be posted by Leopoldo Costa.