The National Institutes of Health’s National Institute of Neurological Disorders and Stroke has awarded Duke Anesthesiology’s Andrea Nackley, PhD, a three-year, $1,106,152 R61/R33 IGNITE (Innovation Grants to Nurture Initial Translational Efforts) grant for her project titled, “A Novel Clinically-Relevant Mouse Model of Chronic Overlapping Pain Conditions for Screening Analgesics.”
Chronic overlapping pain conditions (COPCs) affect nearly one in every three Americans, predominantly females, and are characterized by interactions between genetic and environmental events. Approximately 66% of patients with COPCs (eg, fibromyalgia) have genetic variants that cause low activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. Individuals with the ‘low COMT activity’ genotype report greater pain at baseline, and enhanced pain following stressful and/or injurious events that potentiate catecholamine release from sympathetic nerves.
The objective of Nackley’s project is to develop and validate a novel mouse model of COPCs in which genetically predisposed COMT+/- mice undergo stressful and injurious events resulting in clinically-relevant behavioral and molecular phenotypes for in vivo screening of analgesic therapeutics.
During the 1.5-year R61 phase, Nackley will establish the magnitude and duration of pain at several body sites, sensitization of primary afferent nociceptors innervating those body sites, and pain-related depressive- and anxiety-like behaviors in her COPC mouse model. During the 1.5-year R33 phase, she will evaluate clinically-relevant cytokine biomarkers to determine construct validity and clinically-used analgesics to determine predictive validity of her model.
Nackley’s central hypothesis is that COMT+/- mice, especially females, undergoing transient stressful and injurious events will develop chronic pain at multiple body sites and increased levels of clinically-relevant cytokine biomarkers that will be reduced by existing FDA-approved analgesics.
“I’m excited to work with my CTPM colleagues, Drs. Xin Zhang, Yaomin Wang and Andrey Bortsov on this IGNITE project. Together, we plan to develop a novel mouse model of COPCs that will have a significant impact on discovery of safe, effective analgesics with translational relevance,” says Nackley, associate professor in anesthesiology, pharmacology and cancer biology.
Nackley is a part of Duke Anesthesiology’s Center for Translational Pain Medicine (CTPM). She also serves as the director of the Translational Pain Research Laboratory.