New Target For Pain Relief Found

THURSDAY, May 6, 2004 (HealthDayNews) -- German researchers report the discovery of a key link in the molecular pathway that sends pain-generating signals to the brain.

The finding could open the way to a new generation of more effective painkillers, said Ulrike Mller, a neurobiologist at the Max-Planck-Institute for Brain Research in Frankfurt and a member of the team reporting the discovery in the May 7 issue of Science.

The molecule they describe is a receptor that sits on the surface of cells in the spinal cord. The function of that receptor, designated GlyR alpha3, is to block transmission of pain signals generated by injury or inflammation, Mller explained.

But GlyR alpha3 activity is blocked by prostaglandins, molecules that are produced by pain-causing activity, she said.

"What we have to do now is find a substance that keeps the receptor open," she said. "There is no known substance that would do that now."

Today's painkillers such as aspirin act by inhibiting production of prostaglandins, "but these can have serious side effects," Mller said. "One could imagine a second generation of analgesics that specifically target this receptor."

Scientists have known about the existence of GlyR alpha3 for years, she said, but its function was not known. "Our goal was not to cure pain," Mller said. "Our goal was to find the function of the receptor."

Research with mice bred to have a deficiency of GlyR alpha3 outlined that function. Those mice experienced less pain from inflammation or injury than normal mice, the researchers found.

Pain is a complex function, it appears. When something happens to cause pain -- a flare-up of arthritis or a pinched finger -- prostaglandins are generated both at the site of pain and in the spinal cord.

"One has known that prostaglandins are produced in the spinal cord, but it has not been known what the target of those prostaglandins might be," Mller said.

Now they know. But one problem in putting the discovery to work is that this receptor is a member of a family of molecules that have only slight -- but nevertheless critical -- differences in structure.

"It will be crucial to find compounds with high selectivity for the alpha3 subunit," Mller said.

More information

News about pain and efforts to relieve it is available from the American Pain Foundation or the American Academy of Pain Management.