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Date:5/20/2013

the amygdala by a particular type of receptor for the neurotransmitter serotonin will enable the successful treatment of neuropathic pain.

Although increased serotonin activity in the brain is generally thought of as a good thing it's the mechanism used by many antidepressant drugs activation of the serotonin 2C receptor in the amygdala can cause problems, according to Neugebauer. "In neuropathic pain we see that this receptor is activated on cells that regulate output from the amygdala to brain areas where responses to potentially harmful situations are generated," Neugebauer said. "This activity should be turned off when such response is no longer needed or useful, but these serotonin 2C receptors continue to drive amygdala output, creating a chronic pain state."

In experiments with laboratory rats in which neuropathic pain behavior has been induced by nerve damage, Neugebauer and Green plan to investigate the possibility of "re-normalizing" the amygdala by injecting it with specially designed viruses containing genetic material that blocks cells' generation of serotonin 2C receptors.

"The viruses that we're using are adeno-associated viruses, very common vectors that about 80 percent of the people in our society have been exposed to," Green said. "We've modified them so that they can't replicate, and inserted a gene that instructs the amygdala cells to make small pieces of RNA that interfere with the production of serotonin 2C receptors."

According to Green, who has been working with similar gene-therapy techniques for more than 10 years, the viral injections produce permanent effects in the brain and no off-target effects. The researchers plan to test the rats' response to the treatment with a variety of behavioral experiments that will examine both its effect on chronic pain behavior and behaviors associated with depression.

In addition to the behavioral investigation, the project will include electrophysiological
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Contact: Jim Kelly
jpkelly@utmb.edu
409-772-8791
University of Texas Medical Branch at Galveston
Source:Eurekalert

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