A woman born incapable of feeling pain has been hurt for the first time – thanks to a drug normally prescribed for opioid overdoses. She was burned with a laser, and quite liked the experience.
The breakthrough may lead to powerful new ways to treat painful conditions such as arthritis.
Only a handful people around the world are born unable to feel pain. These individuals can often suffer 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 suffer an increased range of knocks, tumbles and encounters with sharp or hot objects.
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 channels, known as Nav1.7 channels, nerve cells are unable to communicate pain. Researchers quickly sought to make compounds that blocked Nav1.7 channels, thinking they might be able to block pain in people without the disorder.
"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 saw some success, none brought about the total pain loss seen in people who lack the channel naturally.
To find out why, Wood and his colleagues studied mice that had been genetically modified to lack Nav1.7. These animals don't feel 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 lacking the channel don't feel pain, either.