Feel the burn: alcohol sets pain-sensing nerves aflame. (This Week).

A splash of aftershave stings the face. A shot of whiskey shocks the throat. A swab of antiseptic on a raw wound causes a person to wince.

Scientists now appear to have found the common thread among these sensations: Alcohol makes certain pain-generating nerves trigger more easily than normal. In some cases, it tricks the nerves into behaving as if they are exposed to extreme heat. Suddenly, alcohol's nickname, firewater, has become especially apropos.

The new findings, reported in an upcoming Nature Neuroscience, emerge from research led by John B. Davis of Glaxo-SmithKline in Harlow, England, and Peirangelo Geppetti of the University of Ferrara in Italy. The scientists focused on ethanol, the world's favorite form of alcohol, and its influence on a protein called the vanilloid receptor 1 (VR1). This receptor, which sits on the surface of some sensory nerve cells, first drew public attention when researchers learned that it responds to both high temperatures and capsaicin, the substance that makes certain peppers taste hot (SN: 11/8/97, p. 297).

"Many companies think it's a substantial target for developing a pain therapeutic," says Davis.

There have been some dues that alcohol affects nerves beating VR1. For example, injecting alcohol near damaged nerves that cause chronic pain produces a temporary burning sensation but sometimes leads to pain relief. And Geppetti has had patients with esophagitis, or inflammation of the esophagus, who have reported that strongly alcoholic drinks cause an unusually intense burning in their throats.

Davis and Geppetti now have demonstrated an alcohol-VR1 connection in the laboratory. They've shown that ethanol triggers certain tissues, such as skin, to release the same neurochemical signals secreted when heat or capsaicin stimulate VR1-laden sensory nerves. Triggering nerves in such tissues with capsaicin eliminates a subsequent ethanol response--further indication that the alcohol acts on the same nerve cells.

In another experiment, the researchers applied to cells a solution containing just 3 percent ethanol. They found that the temperature needed to trigger VR1 falls from around 42[degrees] to around 34[degrees]C.

"The heat threshold for VR1 is lowered by ethanol down to temperatures which are at or below body temperatures [about 37[degrees]C]," says Davis.

From these results, the scientists speculate that adding alcohol to inflamed or damaged tissue produces a situation in which a person's body temperature activates VR1 and creates a painful, burning sensation. This may offer the first molecular explanation for why people with esophagitis should avoid alcoholic drinks, says Davis.

Geppetti adds that future drugs that block VR1 activity might help such people.

So far, the studies have been restricted to tissue in laboratory dishes. Davis notes, "We haven't shown directly that ethanol activates VR1 in a body."

Scientists might be able to obtain such evidence using mice that were genetically engineered to lack VR1, says David Julius of the University of California, San Francisco. One of the scientists who identified VR1 and showed that it responds to heat and capsaicin, he's interested in learning whether alcohol, capsaicin, and heat activate the receptor in the same way.