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UCSF finding could lead to a new class of painkillers

UC San Francisco researchers have identified a new molecular pathway through which chemical signals alert the body to pain, and inhibiting the key protein in this pathway could bring relief in a broad spectrum of pain syndromes, they say.

The finding, drawn from a study in mice and rats, applies to inflammatory pain associated with such conditions as arthritis and colitis, torn ligaments and sprained ankles, and post-operative pain. However, the researchers expect the finding will apply even more broadly.

"This discovery is extremely important," said the director of the National Institutes of Health Pain Center at UCSF, Jon Levine, PhD, a professor of oral and maxillofacial surgery and medicine and a senior author of the paper. "I think this signaling pathway will be shown to play a role in many kinds of pain."

The study, published in the Sept. 24 issue of Neuron, was funded by the Ernest Gallo Clinical and Research Center at UCSF and the National Institutes of Health.

The body's immune system responds to many forms of tissue injury by producing an inflammatory response, which includes the release of chemical signals into injured tissue, where they sensitize pain-sensing neurons. As a result, stimuli that normally would not cause pain, such as the brush of a shirt being drawn onto the body, become painful when the skin is sunburned; likewise, the movement of a joint, normally unnoticed, would cause pain in the presence of arthritis.

Chemical signals act on pain-sensing neurons by latching on to specific cell-surface receptors that convey the signals into the cell. Once inside, the chemical signal initiates a cascade of molecular events that culminates with the neurons transmitting pain signals out of the cell body and into the central nervous system, where pain is felt.

Current inflammatory-pain drugs -- the nonsteroidal anti-inflammatory drugs, or NSAIDS, including the new COX-2 inhibitors -- act by blocking
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
23-Sep-1999


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