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1st appeared
17
April 2000
Protein May Be Target for Pain Therapy 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 UCSF, also showed that the receptor contributes to the pain experienced when tissue is injured or inflamed. The findings were 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 postdoctoral 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 channel on the nerve surface. When certain compounds bind to it, the receptor channel opens, allowing a stream of charged sodium and calcium molecules to rush into the nerve cell. This generates an electrical signal that travels to the brain to produce pain. In the experiments reported in Science, researchers found that not only does the chili pepper’s active ingredient, capsaicin, bind to the receptor, but so do protons. "The interaction of the VR1 receptor with protons lowers the temperature threshold at which heat causes pain," said neuroscientist Allan Basbaum, PhD, whose UCSF lab collaborated in the mouse studies. "Patients can usually avoid temperatures that would produce pain from injury, but sensory nerves in the body’s internal organs express VRI as well, and if these organs become inflamed from infection, the nerves that innervate them could become active at the body’s normal temperature and cause persistent pain." Basbaum is professor and chair of anatomy at UCSF. The research provides one of the first molecular pieces in the puzzle of pain sensation, Julius says. While much progress has been made in understanding the senses of taste and smell and sight at the molecular level, the molecules that underlie the perception of pain are just now being studied. "This is just a beginning," says Julius, "but it identifies one of the basic factors involved in the signaling of pain in a normal animal." "Each receptor molecule is a potential target for drugs to reduce pain," adds Basbaum. "Negative side effects are currently the major limit to pain therapy, but if these molecules are uniquely expressed by ‘pain’ neurons, the likelihood of side effects is dramatically reduced." Links: Discovery Holds Promise for Better Understanding and Treatment of Pain Molecule Involved in Hot Pepper and Hot Bath Burning Feeling Provides New Insight into Pain Seeking Ways to Take Away the Hurt Source: Wallace Ravven, News Services |
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