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Identification of Pain Gene Hints at Novel Approach to Treatment

As unpleasant as it is, pain can be advantageous. Acute pain in response to harmful stimuli alerts people to environmental dangers and induces protective behavioral changes. Chronic pain, however, has no such benefits and the difficulties encountered in treating it frustrate patients and their doctors alike. But according to research published today in the journal Cell, a new approach to pain management may one day address this problem. Scientists have discovered a gene involved in pain relief¿a so-called transcriptional switch that controls chemicals involved in pain processing¿that could serve as a novel drug target.

The research, conducted by Michael Salter of the University of Toronto and colleagues, focused on the downstream regulatory element antagonistic modulator, or DREAM, molecule. To identify DREAM's physiological function, the team genetically engineered mice that lacked the gene encoding DREAM. Though the knockout mice showed normal responses to tests of their motor function, learning and memory, they exhibited far fewer pain behaviors¿regardless of what was causing the discomfort or what type of tissue was affected. "The fact that even mice with neuropathic pain¿the kind of sharp, chronic pain resulting from nerve injury¿ experience this effect is exciting," Salter explains, "because the medical community currently doesn't have any widely effective treatments for this debilitating type of pain."

In the region of the spinal cord involved in transmitting and controlling pain messages, the mice who lacked DREAM produced more dynorphin, one of the body's natural pain killers. Unlike current pain treatments, which stimulate cell receptors in the brain for endorphins (the family of proteins to which dynorphin belongs), DREAM modulates pain directly. It binds to DNA and regulates expression of dynorphin. What is more, although many pain medications are addictive, the DREAM-less mice did not become addicted to the pain control chemicals their bodies produced. "These findings point to a novel pharmacological approach to pain management," Salter says, "where researchers will be looking for drugs that could block the ability of DREAM to bind to DNA or simply prevent the production of DREAM."

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