Formula for painless existence

Physical pain is a near universal problem, whether its sudden pangs or chronic aches. Yet, researchers’ efforts to quash it completely have fallen short — possibly due to a moonlighting channel in nerve cells. But that may be about to change.

The sodium ion channel, called Nav1.7, helps generate the electrical signals that surge through pain-related nerve cells. It’s known to play a key role in pain, but researchers’ past attempts to power-down its charged activities did little to soothe suffering. In a bit of a shocking twist, resear-chers figured out why the channel has a second, un-channel-like function — regulating painkilling molecules called opioid peptides. That revelation, published in Nature Communications, provided researchers with the know-how to reverse painlessness in a woman with a rare condition, plus make mice completely pain free.

The link between Nav1.7 and opioid painkillers is “fascinating,” Claire Gaveriaux-Ruff, a pain researcher and professor at the University of Strasbourg, told Ars. And, she added, “This discovery brings hope to the many patients suffering from pain that are not yet adequately treated with the available pain medications.”

That source of hope has been a long time coming, John N. Wood, lead author of the study and a neuroscientist at University College London, told Ars. Researchers have been interested in Nav1.7 for years, he said. Excitement peaked in 2006 when scientists reported finding a family who lacked the channel and could feel no pain at all. After that, researchers excitedly scrambled to relieve pain with Nav1.7-blocking drugs. But the drugs inexplicably failed, Wood said. “So we thought, well maybe this channel isn’t just a channel, maybe it’s got some other activities as well.”

Using genetically engineered mice, Wood and colleagues found that completely shutting off Nav1.7 not only made mice pain-free, it cranked up their amount of opioid peptides in nerve cells. These molecules are natural painkillers that help the body moderate pain responses. In these Nav1.7-lacking mice, opioid levels were extremely high, blunting all twinges and throbs. When the researchers gave the mice a drug that blocks those opioids, the animals could feel pain normally.

Even more promising, Wood and colleagues saw the same result in a 39-year-old woman with a rare mutation that shuts off Nav1.7 and she had been pain-free all her life. But, when the researchers gave her a dose of the opioid-blocking naloxone, she felt pain for the first time — the sting of a tiny laser. She hopes that the drug treatment can be used on children with the pain-free condition to keep them from injuring themselves.