Nerve protein shown crucial to sensations of pain from heat, injury

Probing the molecular pathways of pain, scientists have shown that a protein lodged on the surface of many sensory nerves triggers the nerves to fire pain signals when it is exposed to Death Valley-like heat or the fiery properties of peppery food. The research is the first to demonstrate that the protein, known as the capsaicin receptor, performs this function in living animals, and it boosts confidence that blocking the receptor would ease some kinds of pain.

The research, led by molecular biologists and neuroscientists at UC San Francisco, also showed that the receptor contributes to the pain experienced when tissue is injured or inflamed.

The findings are reported in the April 14 issue of the journal Science, and are highlighted on the issue's cover.

"We have demonstrated how a single molecule affects the behavior of the whole animal," said David Julius, PhD, professor of cellular and molecular pharmacology at UCSF and senior author of the Science paper. "It looks like the capsaicin receptor could be a target for drugs to reduce the sensitivity to some kinds of pain caused by tissue injury."

(In 1997, Julius and Michael Caterina, MD, PhD, then a post-doctoral researcher in Julius' lab, attracted attention by cloning the gene for the capsaicin receptor. A number of pharmaceutical companies have since begun screening drugs to inactivate the receptor.)

The new study shows that activation of the capsaicin receptor contributes to pain in normal, healthy mice, and demonstrates that the receptor is activated by heat and noxious chemicals, as well as protons, normally released from injured tissue.

The research confirms that the receptor is essential for sensing temperatures between about 110 and 120 degrees Fahrenheit -- temperatures most animals must avoid quickly to survive -- and for sensing the heat caused by ingredients in particularly hot foods.

The capsaicin receptor, better known as the vanilloid receptor, or VR1, acts as a channe

Contact: Wallace Ravven
University of California - San Francisco

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