Female Specific RNA-Binding Protein, AUF1, Increases Peripheral Hypersensitivity After Repetitive Ischemia With Reperfusion Injury

Abstract

By Diya Joshi, Medical Sciences; Alex Weyler, Cincinnati Children's Hospital; Luis Queme, Cincinnati Children's Hospital

Advisor: Michael Jankowski

Presentation ID: 31

Abstract: Musculoskeletal pain affects up to 33% of the global population. Myalgia is experienced more often in females. A major cause of disease-based myalgia is from alterations in peripheral blood flow/oxygenation which is observed in disorders such as fibromyalgia . A better understanding of the sex specific mechanisms of ischemic myalgia could lead to the development of more targeted pain therapies. Our previous data showed that mice experiencing repetitive ischemia with reperfusion injury (I/R) in the fore-limb due to occlusion of the brachial artery, display prolonged hypersensitivity after the second injury. Results corresponded with an upregulation of unique factors in the dorsal root ganglia (DRGs) in males vs. females. One factor in particular found to be enhanced in females and linked to sex specific responses in other cellular systems was the RNA binding protein AU rich element binding protein 1 (AUF1). Using a nerve-specific siRNA mediated knockdown strategy, we found that inhibition of I/R-induced AUF1 expression was able to prevent the prolonged pain-like behaviors observed in females while it had no effects on prolonged hypersensitivity in males. We further found that the I/R-related upregulation of factors induced in female DRGs was blocked by AUF1 inhibition while enhanced DRG gene expression after repeated I/R in males was not altered. The data suggests that sex specific gene expression patterns may underlie distinctions in hypersensitivity observed after repetitive I/R injury in males and females. Results could uncover new ways to develop pain therapies targeted to men vs women.