Doctors are dripping the chemical that gives chili peppers their fire directly into open wounds during knee replacement and a few other highly painful operations.

Don't try this at home: These experiments use an ultra-purified version of capsaicin to avoid infection - and the volunteers are under anesthesia so they don't scream at the initial burn.

How could something searing possibly soothe? Bite a hot pepper, and after the burn your tongue goes numb. The hope is that bathing surgically exposed nerves in a high enough dose will numb them for weeks, so that patients suffer less pain and require fewer narcotic painkillers as they heal.

"We wanted to exploit this numbness," is how Dr. Eske Aasvang, a pain specialist in Denmark who is testing the substance, puts it.

Chili peppers have been part of folk remedy for centuries, and heat-inducing capsaicin creams are a drugstore staple for aching muscles. But today the spice is hot because of research showing capsaicin targets key pain-sensing cells in a unique way.

California-based Anesiva Inc.'s operating-room experiments aren't the only attempt to harness that burn for more focused pain relief. Harvard University researchers are mixing capsaicin with another anesthetic in hopes of developing epidurals that wouldn't confine women to bed during childbirth, or dental injections that don't numb the whole mouth.

And at the National Institutes of Health, scientists hope early next year to begin testing in advanced cancer patients a capsaicin cousin that is 1,000 times more potent, to see if it can zap their intractable pain.

Nerve cells that sense a type of long-term throbbing pain bear a receptor, or gate, called TRPV1. Capsaicin binds to that receptor and opens it to enter only those pain fibers - and not other nerves responsible for other kinds of pain or other functions such as movement.

These so-called C neurons also sense heat; thus capsaicin's burn. But when TRPV1 opens, it lets extra calcium inside the cells until the nerves become overloaded and shut down. That's the numbness.

"It just required a new outlook about ... stimulation of this receptor" to turn those cellular discoveries into a therapy hunt, says NIH's Dr. Michael Iadarola.

Enter Anesiva's specially purified capsaicin, called Adlea. Experiments are under way involving several hundred patients undergoing various surgeries, including knee and hip replacements. Surgeons drip either Adlea or a dummy solution into the cut muscle and tissue and wait five minutes for it to soak in before stitching up the wound.

Among early results: In a test of 41 men undergoing open hernia repair, capsaicin recipients reported significantly less pain in the first three days after surgery, Aasvang reported this month at a meeting of the American Society of Anesthesiologists.

In a pilot U.S. study of 50 knee replacements, the half treated with capsaicin used less morphine in the 48 hours after surgery and reported less pain for two weeks. Ongoing studies are testing larger doses in more patients to see if the effect is real.

There's a huge need for better surgical pain relief, says Dr. Eugene Viscusi, director of acute pain management at Thomas Jefferson University in Philadelphia, one of the test sites. Morphine and its relatives, so-called opioid painkillers, are surgery's standby. While they're crucial drugs, they have serious side effects that limit their use.

Specialists are watching the capsaicin research because it promises a one-time dose that works inside the wound, not body-wide, and wouldn't tether patients to an IV when they're starting physical therapy.

"It's in and it's done," Viscusi explains. "You can't abuse it. You can't misuse it."

"There's been an enormous effort to try and develop alternatives to opioids with the same strength but not too much success," adds Dr. Clifford Woolf of Harvard and Massachusetts General Hospital. "We think we're moving toward it."

His team is trying a different approach: Standard lidocaine injections numb all the surrounding tissue. Woolf and colleagues slipped lidocaine inside just pain-sensing neurons, by opening them with a tiny dose of capsaicin. Rats given the injections ran around normally while not noticing heat applied to their paws, they reported in the journal Nature this month.

That's years away from trying in people, and would have to be done in a way to avoid even a quick capsaicin burn.

In a third approach, Iadarola and NIH colleagues hope to soon test a capsaicin cousin called resiniferatoxin in advanced cancer patients whose pain no longer is relieved by opioids. Injections into the spinal columns of cancer-riddled dogs did more than temporarily numb - it severed some nerve connections.

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 Lauran Neergaard covers health and medical issues for The Associated Press in Washington.