The National Institute of Neurological Disorders and Stroke (NINDS) has awarded Duke Anesthesiology’s Andrea Nackley, PhD, a $160,000 R03 grant for her project, titled “Defining the role of adipocyte Adrb3 in chronic pain.”
According to the project’s abstract, common chronic pain syndromes, such as fibromyalgia and temporomandibular disorder, constitute one of the nation’s most significant health care problems, yet are ineffectively treated because the underlying molecular mechanisms remain largely unknown. Dr. Nackley and her team of investigators hypothesize that these conditions are driven by abnormalities in catecholamine physiology that result in increased activation of peripheral Adrb3 and decreased expression of the microRNA miR-133a that regulates pain-relevant genes.
Their research objective is to generate, validate, and phenotype an inducible adipocyte-specific Adrb3 knockout mouse and an adipocyte-specific miR-133a viral construct. These unique tools will allow Dr. Nackley and her team to define the mechanisms whereby peripheral Adrb3 promotes chronic pain. Their work aims to 1) advance knowledge of the peripheral mechanisms that drive chronic pain, 2) inform the design of subsequent studies that determine the contribution of adipocyte Adrb3 to nociceptor activity and neuroinflammation, and 3) identify novel targets for developing peripherally-restricted therapies that will overcome the limitations of specificity and central side effects associated with current treatment regimens for functional pain syndromes.
Results from these studies are expected to provide new insights into the peripheral mechanisms that drive chronic pain, and elucidate new targets for the development of peripherally-restricted therapies with improved specificity and side-effect profiles for the treatment of functional pain syndromes. Such findings will have a positive impact because they will inform the design of more comprehensive mechanistic studies and the development of new treatment strategies to improve the quality of life for 100 million patients in the U.S. alone who experience chronic pain.
Dr. Nackley, associate professor in anesthesiology, is the director of The Nackley Laboratory (within the Center for Translational Pain Medicine) which has three main objectives: 1) to determine the factors that put some people but not others, at risk for maladaptive chronic pain conditions, 2) to elucidate the mechanism(s) whereby genetic, biological, and environmental factors drive chronic pain and 3) to improve pharmacologic management of pain.