A key ingredient in chili peppers, chased with a local anesthetic, could be just the ticket for ending pain in the dentist's chair and on the operating table without the potentially dangerous side effects and all-numbing aftermath of traditional anesthesia, says a new Harvard Medical School study.

Researchers report in Nature that a combination of capsaicin (the ingredient that gives chili peppers their bite) and QX-314, a derivative of lidocaine (a local anesthetic used by dentists and to relieve inflamed, itchy skin), effectively silences pain-sensing nerve cells without disturbing other neurons that control motor function and other sensations.

QX-314 is known to reduce the activity of pain-sensing neurons in the nervous system and theoretically heighten pain thresholds. But there's a catch: Researchers found that "it wouldn't work from outside a nerve cell but it would work if you could get it inside," says Bruce Bean, a professor of neurobiology at Harvard Medical School and co-author of the new study.

David Julius, a physiology professor at the University of California, San Francisco, recently discovered that capsaicin selectively binds to a protein known as TRPV1 that resides on the membranes of pain-sensing neurons. When capsaicin binds to TRPV1, it causes the protein to open a gate leading to a small channel in the nerve cell's membrane. (Neurons that do not contain TRPV1 are unaffected.)

"The novelty of the idea here was that it might be possible that the QX-314 molecule might be small enough that you might be able to put it in through that small channel," Bean says.

If so, researchers reasoned, injecting capsaicin followed by QX-314 should allow the chili pepper compound to open the doors of pain-sensing neurons, clearing the way for the anesthetic to enter and shut down the cells. The team initially tested its theory using petri dish cultures of nerve cells from rat spinal cords and found that electrical activity in pain-sensing nerve cells dipped after injections of capsaicin followed by QX-314. This indicates the cells would be too weak to send messages to the brain.

Researchers then conducted two experiments on rats. In one, they injected capsaicin and QX-314 into the paws of some of the animals, then placed them on surfaces that were heated until the rats felt pain. All of the injected animals were numb to the highest level of heat to which they were exposed. In the second test, the cocktail was administered into the sciatic nerves of some rats in the test group. (The sciatic is the body's longest nerve, responsible for sensation in the back and lower extremities). The animals were then poked with three nylon probes at different strengths; half of the group did not even bristle at the strongest jab.

None of the rats that had been injected with the capsaicin–QX-314 cocktail experienced temporary paralysis—a potential side effect of traditional anesthesia—indicating that the combination had successfully targeted only pain-sensing nerve cells. The heightened pain threshold appeared to last up to four hours, according to Bean.

U.C. San Francisco's Julius (who was not involved in the study) called the new approach simple and clever, but noted that some tweaks of the methodology are needed before this can become a pain blocker in humans. One major obstacle that must be overcome, he says, is the irritating nature of capsaicin, which causes burning sensations when one touches (not to mention eats) it. "If the QX compound silences the nerve fast enough after the capsaicin opens the channel," he says, "then it should work for some local anesthetic applications."

According to Bean, study co-author Alexander Binshtok, a Harvard postdoctoral researcher in neural plasticity, is already at work eliminating capsaicin's negative effects by reversing the order of the injections: leading with QX-314, quickly followed by capsaicin to shove it through the cell.

Ideally, Bean says, researchers will find a way to erase any initial pain before the spicy new method replaces epidurals and novocaine injections. Toward that end, he says, the team is searching for a molecule similar to capsaicin "that opens the TRPV1 channels but doesn't have as much of an irritant effect."