If You Can't Take the Heat, Blame the 'Chili-Pepper Receptor'

April 14, 2000 (Boston) - The next time you see a mouse at your favorite taco joint, don't panic or call the health authorities -- he may be there for the hot sauce.

A team of researchers at the University of California, San Francisco, has shown that mice bred to be missing both copies of a certain gene can happily lap up pepper-laced water, don't seem to mind when their paws are injected with capsaicin -- the chemical that puts the "hot" in red-hot chili peppers -- and seem to feel almost no pain when exposed to very high temperatures or caustic chemicals on their skin.

In contrast, their normal cousins licked and shook their paws vigorously when exposed to capsaicin, and after drinking water that contained the chemical rubbed their snouts and refused to take another drop. Mice with the missing gene also had less swelling in their paws than normal mice in response to an injury, but still felt the pain of a tail pinch as acutely as any other mice.

The findings suggest to researchers that cells carrying a receptor, or "docking site," for capsaicin molecules and similar irritating compounds could make good targets for a potential new class of pain-killing drugs, say David Julius, PhD, and colleagues in the March 14 issue of the journal Science.

The capsaicin receptor, called VR1 for short, could serve as the target for painkillers that would stop pain signals at their source, but with fewer side effects than currently available painkillers in the aspirin or morphine families, the researchers say.

Curiously, although both normal mice and people get a burning sensation in the mouth when capsaicin is eaten in the form of jalapenos, Scotch bonnets, or other fiery peppers, the chemical is also highly effective at deadening pain from arthritis and other inflammatory conditions when it's rubbed on the skin.

"There are two possible effects that drugs that act at this receptor have," explains Julius, a professor of cellular and molecular pharmacology at UCSF, in an interview with WebMD. One is to control the activity of the receptor and the other is to affect the way the nerve sends out signals in general, he says.

"And I think that probably most of the effects of capsaicin as a treatment probably have to do with the latter. ? Some studies suggest that when you treat an area -- say, where capsaicin is injected into the skin -- there's a loss of sensation to [harmful] stimuli, and with that, if you do some imaging, you can see that there's actually a loss or withdrawal of the nerve fibers from that area."

The VR1 receptor may be a good target for painkillers because it is found primarily at the site of an injury, says Eva Mezey, MD, PhD, who researches VR1 as a medical officer at the National Institute of Neurological Diseases and Stroke.