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Cool and Minty Go Hand in Hand

Scientists identify a nerve cell receptor for cold and menthol

MONDAY, Feb. 11, 2002 (HealthDayNews) -- When you bite into that well-advertised, ice-cold peppermint patty, not only do you get the sensation of flying down a frozen bobsled run, but you also activate a newly identified nerve cell receptor stimulated by both cold and menthol.

While explaining the physiology of peppermint was not a recent study's primary goal, the link explains the "cool" sensation of mint. Moreover, the discovery could lead to a better grasp of how humans feel pain -- and better ways to treat it.

For several years, David Julius' laboratory at the University of California, San Francisco, has studied the chemical signals involved in the body's ability to sense pain. As part of those studies, he became interested in how we respond to capsaicin -- which gives hot peppers their punch -- as well as how we sense hot and cold temperatures.

The team identified the receptor for capsaicin, and showed it was also activated by heat.

"Having spent a few years investigating the molecular mechanisms of heat sensation, we became curious about the flip side of that question," says Julius, a professor of cellular and molecular pharmacology. "That is, how do we sense cold and how do plant products like menthol elicit the sensation of cold?"

The findings appear in tomorrow's issue of the journal Nature online.

Sensory nerves endings, such as those found in the skin, eyes and lips, change in response to contact with a cold object. In this study, Julius and his colleagues identified a subset of these nerve cells that express a specific receptor, which they called cold-and menthol-sensitive receptor (CMR1).

The CMR1 receptor could be called a "cool" receptor, since it responds to temperatures between 46 degrees and 84 degrees Fahrenheit. At the same time, it's also activated by exposure to menthol, which gives certain chewing gums and candies their "icy, cool" taste.

The receptor is an ion channel in the surface of the nerve cells. In response to cold or menthol, the channel opens to create a pore in the cell, allowing sodium and calcium ions to flow inside.

Those ions create an "action potential" within the cell, an electrical charge that flows along the nerve cell to its neighbors. They pass this signal on until it reaches the spinal cord and the brain.

"Exactly where this information is correlated and decoded [in the brain] is still an area of significant research," Julius says.

David M. Cain, a research associate in oral sciences at the University of Minnesota, says the link doesn't surprise him, since capsaicin is linked to an extreme heat receptor.

"There may be yet another [receptor] for extreme cold," says Cain.

The latest findings could eventually open new avenues of pain research, Julius says, but the field is still in its infancy.

"We are just at the start of identifying the molecules that are involved in transmitting these kinds of stimuli," he explains.

Aside from opiates like morphine or nonsteroidal anti-inflammatory drugs (NSAIDs), Julius says there remain few treatments for pain. "In part, that may reflect the fact that, until recently, we haven't had that much of a molecular handle on understanding the players -- the proteins -- that are involved," he says.

"The more of those that are identified, the greater the opportunities to develop drugs that target specific parts of the signaling pathway," he says. "You have to know how the system works before you can take new approaches to developing drugs, which I think is something that really has to be done in the pain area."

Cain says that identifying cold receptors could also lead to a better understanding of frostbite injuries.

What To Do

Check out this patient information from the American Pain Foundation or the American Chronic Pain Association.

On a lighter note, discover the history of York Peppermint Patties from Hershey Foods Corp.

SOURCES: Interviews with David Julius, Ph.D., professor, Department of Cellular and Molecular Pharmacology, University of California, San Francisco; David M. Cain, research associate, Department of Oral Sciences, School of Dentistry, University of Minnesota, Minneapolis; Feb. 10, 2002, Nature online
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