Glial-mediated neuroinflammation in a novel in vitro model of chronic pain
Category: Oral Presentation
Author(s): Lydia Jenkins, Emily Perkins, Quinn Pogge, Julie Moreno
Presenter(s): Lydia Jenkins
Mentors(s): Katriana Popichak, Mark Zabel
Chronic pain (CP) affects 20% of people worldwide. While current understanding of pathological pain revolves mostly around neuronal mechanisms, supporting peripheral cells are often overlooked in CP studies. Macrophages regulate peripheral inflammation, while microglia—the central nervous system (CNS) resident macrophages—protect neurons. Along with astrocytes, these non-neuronal cells drive neuroinflammation through NF-κB signaling, as shown in recent CP and other pathological pain studies. Current in vivo studies demonstrate Complete Freund’s Adjuvant (CFA) to be an effective model for CP, however, there are no established in vitro models. Thus, we hypothesize that an in vitro CP model utilizing CFA will demonstrate increased inflammatory signaling and oxidative stress, promoting neuronal cell death regulated by both macrophages and glial cells. To test this hypothesis, we measured cell viability of N2A cells, an immortalized neuronal cell line, treated with CFA, and saw a dose-dependent decrease in viability upon exposure. Contrary to the above hypothesis, N2A cells exposed to glial-and macrophage-conditioned media failed to demonstrate cell death, suggesting an early mechanism of neuroinflammation. Thus, we measured NF-kB-regulated inflammatory gene expression of N2A cells exposed to conditioned media and direct treatment to reveal how peripheral immune response to CP alters neuronal behavior. Taken together, these data elucidate cellular mechanisms behind CP-associated inflammatory signaling pathways, and potential targets for more effective therapeutic treatments.