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 Na v 1.7, 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, researchers 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 Na v 1.7 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 Na v 1.7 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 Na v 1.7-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 Na v 1.7 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 Na v 1.7-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. (The opioid-blocking drug, naloxone, treats overdoses of opioid drugs, such as morphine and codeine.)

Even more promising, Wood and colleagues saw the same result in a person. The test subject, a 39-year-old woman with a rare mutation that shuts off Na v 1.7, 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 was happy to go back to her normal, painless state after the drug wore off, Wood reported. But, she hopes that the drug treatment can be used in children with the pain-free condition to keep them from unknowingly injuring themselves.

Now that Wood and his team could conjure pain in the painless, they aimed to do the reverse. They gave normal mice a combination of a Na v 1.7-blocker and a very low dose of an opioid drug. Individually, the drugs did little to nothing to eliminate pain. But, together, they seemed to mimic what was going on in Na v 1.7-lacking mice and people, producing a blocked ion channel and boosted levels of opioid molecules. With the drug combo, the mice felt no pain.

Wood thinks that the Na v 1.7-blocking drugs can’t eliminate pain alone because they may not block the channel’s opioid-regulating role completely—thus the level of opioid peptides might not get high enough to block pain. But, it’s still unclear how the channel regulates the opioid peptides in the first place. Preliminary data suggest that the amount of sodium the channel lets into the cell may play a role, Wood said.

Still, the one-two-punch of the drug duo may do the trick for making people pain-free. Wood has filed a patent on the therapy in hopes that a pharmaceutical company will be interested in developing a treatment. He is also pleased that only a very low dose of opioid drugs seems necessary, thus lowering the dangers of addiction. It could still all fall apart, Wood cautioned, because the combination therapy has only been tested in animals. But, he said, “at the moment, it looks very, very encouraging.”

Nature Communications, 2015. DOI:10.1038/ncomms9967 (About DOIs).