WASHINGTON, D.C. October 16 - After years of searching, scientists have discovered and cloned the gene for a protein that surprisingly initiates the scorching pain felt from touching an over-heated curling iron or from chomping a chili pepper. The finding not only reveals how intense heat and hot peppers prompt pain, but also could lead to new treatments for the more than 97 million Americans who suffer chronic, debilitating headaches, back pain or arthritic pain each year.
"The protein we identified might malfunction and contribute to chronic pain syndromes," says David Julius of the University of California at San Francisco. "With the gene for this protein in hand, it is now possible to address this prospect and develop new and more effective drugs for treating pain." For example, drugs that bind to the protein may be capable of blocking the activation of pain-sensing nerve cells or neurons, thereby interfering with the perception of pain, according to Julius and his colleagues.
Their study, primarily funded by the National Institutes of Health, will be published in the October 23 issue of Nature.
"This is a very important and outstanding study," says Ronald Dubner, a pain expert at the University of Maryland. "The research identifies a protein that is not only sensitive to chemical stimuli but also responds to tissue-damaging levels of heat stimuli."
Specifically the researchers discovered that the active ingredient in hot peppers, capsaicin, carries out its action by binding to a specific receptor - a protein that sits on the surface of a neuron. Capsaicin is known to cause tingling and burning pain by directly stimulating specific pain-sensitive neurons in the mouth and skin. The researchers believe that the activation of the receptor triggers a sequence of biochemical changes in the neurons that leads to the sensation of pain. "Remarkably we found that the same receptor that binds capsaicin on the surface of pain-sensing neurons also detects burning heat," says Julius. "We believe that hot peppers feel hot because capsaicin and heat stimulate the same protein sensor in the neurons."
In the second part of the study the researchers cloned the gene for the capsaicin receptor. Previous research has suggested that molecules that target the capsaicin mechanisms could be promising pain-controlling substances. But the testing of such drugs was difficult because it required the tedious isolation of pain-sensing neurons from mice or rats. "The cloning of the gene for the capsaicin receptor will enable us to produce large quantities of the protein in cells grown in petri dishes, making it easier to test the effectiveness of potential treatments," says Julius.
The researchers also plan to determine how capsaicin or heat turns on the capsaicin receptor. "Biochemical studies will help to pinpoint regions of the receptor that are most important for recognizing these triggers," says Julius. "This information will help to guide the development of new drugs." In addition, the researchers will determine if capsaicin receptors communicate their signal through other proteins within pain-sensing neurons.
Julius' co-authors, Michael Caterina, Mark Schumacher, Makoto Tominaga, Tobias Rosen and Jon Levine also are from the University of California at San Francisco. Julius and Schumacher are members of the Society for Neuroscience, an organization of more than 27,000 basic scientists and clinicians who study the brain and nervous system.