Dr. Andrea Nackley, PhD, Associate Professor of Anesthesiology, Pharmacology, and Cancer Biology at Duke University School of Medicine, presented a talk in the CAPToR Seminar Series on April 29, 2026, focused on emerging mechanisms that drive chronic primary pain. Her talk highlighted how non-neuronal tissues, particularly adipose tissue, actively shape pain through coordinated signaling with the nervous and immune systems.
Speaking to an audience of faculty, trainees, and staff at the University of Florida, Dr. Nackley delivered a seminar titled “Adrb3 Regulation of Adipo–Neuro–Immune Crosstalk in Chronic Pain.” The presentation centered on a growing body of work from her laboratory demonstrating that chronic primary pain conditions are not maintained by neurons alone, but instead arise from sustained interactions among adipocytes, immune cells, and sensory neurons.
Dr. Nackley described landmark findings showing that catecholamine activation of the beta‑3 adrenergic receptor (Adrb3) on adipocytes acts as a critical trigger for chronic pain. Activation of this pathway promotes local immune cell infiltration and pro‑inflammatory cytokine release, increases the excitability of primary afferent nociceptors in dorsal root ganglia, and drives neuroplastic changes within pain‑relevant brain regions. Together, these peripheral and central effects establish a persistent pain state that mirrors key features of chronic primary pain in patients.
A major emphasis of the seminar was the concept of an adipo‑neuro‑immune axis as a unifying framework for understanding chronic pain biology. Dr. Nackley outlined evidence that adipocyte signaling can shape immune tone and neuronal function well beyond metabolic regulation, positioning adipose tissue as an active participant in pain pathophysiology. She also discussed epigenetic mechanisms, including microRNA regulation, through which Adrb3 signaling can produce long‑lasting changes in nociception and pain susceptibility.
Throughout the talk, Dr. Nackley drew clear connections between mechanistic studies in mouse models and translational relevance to human chronic pain conditions. By integrating genetic vulnerability, stress, and minor injury, her work provides insight into why certain individuals develop persistent pain while others recover. These findings have direct implications for identifying new therapeutic targets that move beyond neuron‑centric approaches.
Dr. Nackley concluded by discussing ongoing efforts to translate these discoveries into novel pain therapeutics, including the development of peripherally targeted Adrb3 antagonists. Her seminar underscored the importance of interdisciplinary research in advancing non‑addictive treatments for chronic pain, aligning closely with CAPToR’s mission to accelerate innovative and translational pain therapeutics.
