October 11, 2019
The transition of an acute source of pain to a chronic pain pathology is one of the most challenging medical dilemmas to explain, but new research may provide an answer to the long-term maintenance of pain states.
Scientists at the Icahn School of Medicine at Mount Sinai have identified a brain protein that plays a critical role in the development of chronic pain, providing a potential target for treatment of various conditions.
Chronic pain stems from a variety of adaptations that can develop following acute inflammatory or neuropathic disturbances. Over time, patients who suffer from chronic pain also face associated symptoms, such as sensory deficits and depression.
Current drug treatments for chronic pain conditions often have limited results, problematic side effects or addictive properties that lead to dependence. The protein identified in the Icahn School study, RG54, could offer a new avenue for research into the treatment of chronic pain.
"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," said Venetia Zachariou, a professor of neuroscience and pharmacology at the Icahn School's Friedman Brain Institute. "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."
Researchers focused on RG54 because it plays a vital role in brain circuits that process pathological pain, mood and motivation.
Using genetic mouse models, the research team cut off the RG54 protein and determined that doing so disrupted the maintenance of chronic pain symptoms in males and females. Specifically, they found that stopping RG54 action promotes recovery from sensory hypersensitivity symptoms in a range of neuropathic and inflammatory conditions.
The study was published this month in the Journal of Neuroscience.
Further research will look to examine the role of RG54 in the spinal cord and mood-regulating areas of the brain, with hope of testing the therapeutic value of RG54 inhibitors.