A recent study has revealed that extended nerve damage (in a model of chronic pain) reduces the presence of the gene controller, Myocyte Enhancer Factor 2C (MEF2C) in the nucleus accumbens, a part of the brain responsible for managing emotions, rewards, and pain perception.
Chronic pain impacts about 20% of the population in the United States and 30% worldwide. Besides physical symptoms, chronic pain conditions often coincide with high levels of depression and substance misuse. Dealing with chronic pain and its associated emotional issues is challenging due to the diverse clinical presentations and the intricate regional and molecular aspects of the condition, making comprehensive treatment difficult.
A recent investigation conducted by scholars at the Boston University Chobanian & Avedisian School of Medicine has shown that prolonged nerve injury (in an experimental model of chronic pain) decreases the presence of the gene controller, Myocyte Enhancer Factor 2C (MEF2C) in the nucleus accumbens, a key brain area that oversees emotions, rewards, and pain processing.
Gene controllers regulate gene activity, and when altered due to nerve damage, they can increase the expression of genes that amplify pain signals or decrease those that counteract pain symptoms. Lead author Venetia Zachariou, PhD, Edward Avedisian Professor and chair of pharmacology, physiology & biophysics at the school, explains, “By elevating the levels of this gene controller to counteract the impact of the injury, we managed to alleviate pain and anxiety-like behaviors, while also rectifying neuronal problems and altered communication within the brain’s mesolimbic system.”
As noted by primary author Randal Serafini, PhD, a postdoctoral researcher in Zachariou’s lab,
the absence of a reliable treatment for chronic pain can be attributed to the distinct changes in neuronal networks following prolonged injury. “Certain brain regions directly regulate pain and related conditions, with the nucleus accumbens being one of them.” Zachariou further adds, “A clearer understanding of the mechanisms contributing to pain in these areas brings us closer to discovering more effective treatments.”
The researchers plan to search pharmacological databases next to identify approved drugs with good safety profiles that either boost MEF2C activity or regulate its downstream targets similarly. This approach could expedite the transition of their discoveries to clinical applications.
These findings are featured online in the journal Pain.
The study received funding from the NINDS [R01NS086444 (V.Z.), R01NS111351 (V.Z.), R01NS086444S1 (R.A.S.)], the ASRA Graduate Student Award (R.A.S.), and the NIH [T32GM007280 (R.A.S.)].
