Mouse provides clues about chronic pain

Investigators at Washington University School of Medicine in St. Louis have found that a protein that allows nerve cells to communicate may enhance perceptions of chronic and persistent pain. In the February issue of Nature Neuroscience, they report the protein, called NR2B, makes mice more aware of minor pain for longer periods of time.

"That sustained response appears to mimic what happens in people who experience pain long after the painful stimulus has disappeared," says principal investigator Min Zhuo, Ph.D., an associate professor of anesthesiology and of anatomy and neurobiology. "So interfering with NR2B in humans might be a strategy for treating chronic pain."

NR2B is one of the mix-and-match building blocks of important cellular proteins called NMDA receptors. Like radio receivers, these receptors sit on the cell surface, tuned in to messages sent from neighboring cells and carried by the chemical messenger glutamate. More importantly, NMDA receptors are a neurons activity detectors, and they function only when the number and intensity of neuronal messages reach a prescribed, threshold level.

Because NMDA receptors only become activated at these threshold levels, they tend to be the primary neuronal receptors involved in important brain functions such as learning and memory and in injurious brain processes such as stroke, head injury and drug abuse. They also are the primary receptors involved in persistent pain.

The researchers studied a strain of genetically altered mice that was created by Joe Tsien, Ph.D. and colleagues at Princeton University to make extra NR2B in forebrain areas. The Washington University group found that these mice reacted to acute pain in the same way as normal mice. But the NR2B mice seemed to have stronger or longer periods of behavioral responses to two different models of more persistent, inflammatory pain. None of the mice demonstrated pain symptoms in the absence of an injury.

"We believe that when an i

Contact: Jim Dryden
Washington University School of Medicine

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