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Researchers identify potential targets for new pain therapies

A team led by Robert W. Gereau IV, Ph.D., associate professor of anesthesiology, reports in the April 6 issue of the journal Neuron the identification of a potassium channel that plays a crucial role in what scientists call pain plasticity, the ability of molecules in the spinal cord to amplify or diminish the response to a painful stimulus.

Electrical activity in neurons is produced by subtle changes in the cell's potassium concentration. To maintain correct amounts of potassium, cells are equipped with proteins that poke through the cell membrane like small pores. The proteins are called ion channels or potassium channels, and they create tiny sieves through which potassium can flow from the inside to the outside of the cell.

"The potassium channel we are studying is called Kv4.2," says Gereau, who also is chief of the basic research division of the Washington University Pain Center. "Through a series of experiments, we've been able to determine that Kv4.2 decreases transmission through the pain pathway. It helps regulate the ability of pain-transmitting neurons to transmit their signals to the brain."

We sense pain through primary sensory neurons with nerve endings in the skin, the joints, internal organs or muscles. Those nerve cells interpret signals indicating tissue injury or potential injury and transmit these signals to a part of the spinal cord called the dorsal horn. Pain-transmission neurons in the dorsal horn receive those messages and transmit their own pain signals to the brain.

The signals from neurons in the dorsal horn can be either damped down or enhanced, depending upon many factors, according to Gereau. That's the plasticity that makes some things hurt more than others, even though the painful stimulus itself might not change.

"Say you pinch your finger," Gereau says. "It might not feel painful because even though you activate some of these pain-sensing neurons, that pain signal doesn't just pass throug
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Contact: Jim Dryden
jdryden@wustl.edu
314-286-0110
Washington University School of Medicine
5-Apr-2006


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