Discovery of Brain Protein Could Lead to New Chronic Pain Treatments

By Pat Anson, PNN Editor

Researchers have identified a protein in the brain that appears to play a prominent role in the maintenance of long-term pain -- a discovery that could lead to new treatments that stop short-term acute pain from progressing to chronic pain.

The protein RGS4 (Regulator of G protein signaling 4) is found in brain circuits that process pathological pain, mood and motivation.

"Our research reveals that RGS4 actions contribute to the transition from acute and sub-acute pain to pathological pain states and to the maintenance of pain," says Venetia Zachariou, PhD, a professor in The Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai in New York City.

"Because chronic pain states affect numerous neurochemical processes and single-target drugs are unlikely to work, it's exciting to have discovered a multifunctional protein that can be targeted to disrupt the maintenance of pain."

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In studies on genetically modified mice, Zachariou and her colleagues found that genetic inactivation of RGS4 did not affect acute pain, but it promoted recovery from nerve injuries, chemotherapy-induced neuropathy and peripheral inflammation. Mice lacking RGS4 developed all the expected symptoms of a nerve injury, but recovered within 3 weeks and returned to physical activity.

The transition from acute to chronic pain is accompanied by numerous adaptations in immune, glial and neuronal cells, many of which are still not well understood. Chronic pain patients experience a number of debilitating symptoms besides pain, such as sensory deficits, depression and loss of motivation

Researchers believe future drugs that target RGS4 could prevent acute pain from transitioning to chronic pain. Currently available medications for chronic pain only treat the symptoms – not the underlying condition – and have major side effects.

Dr. Zachariou's laboratory is conducting further investigation into the actions of RGS4 in the spinal cord and mood-regulating areas of the brain to better understand the mechanism by which the protein affects sensory and pain symptoms.

Their findings are published online in The Journal of Neuroscience.