Sex-specific role of RNA-binding protein, pAUF1, on prolonged hypersensitivity after repetitive ischemia with reperfusion injury.

Autor:	Quijas MM; Division of Pain Management, Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Queme LF; Division of Pain Management, Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Woodke ST; Division of Pain Management, Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Weyler AA; Division of Pain Management, Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Buesing D; Department of Pharmacology and Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH, United States. Queme is an Assistant Professor now with the Department of Biomedical Sciences, University of New England, Biddeford, ME, United States., Butterfield A; Division of Pain Management, Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Joshi DP; Division of Pain Management, Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Mitxelena-Balerdi I; Division of Pain Management, Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States., Ulrich-Lai YM; Department of Pharmacology and Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH, United States. Queme is an Assistant Professor now with the Department of Biomedical Sciences, University of New England, Biddeford, ME, United States., Jankowski MP; Division of Pain Management, Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.; Pediatric Pain Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, United States.
Jazyk:	angličtina
Zdroj:	Pain [Pain] 2024 Oct 08. Date of Electronic Publication: 2024 Oct 08.
DOI:	10.1097/j.pain.0000000000003415
Abstrakt:	Abstract: Repetitive ischemia with reperfusion (I/R) injury is a common cause of myalgia. Ischemia with reperfusion injuries occur in many conditions that differentially affect males and females including complex regional pain syndrome and fibromyalgia. Our preclinical studies have indicated that primary afferent sensitization and behavioral hypersensitivity caused by I/R injury may be due to sex-specific gene expression in the dorsal root ganglia (DRG) and distinct upregulation of growth factors and cytokines in the affected muscles. To determine how these unique gene expression programs may be established in a sex-dependent manner in a model that more closely mimics clinical scenarios, we used a developed prolonged ischemic myalgia model in mice whereby animals experience repeated I/R injuries and compared behavioral results with unbiased and targeted screening strategies in male and female DRG. Several distinct proteins were found to be differentially expressed in male and female DRG, including phosphorylated AU-rich element RNA-binding protein (pAUF1), which is known to regulate gene expression. Nerve-specific siRNA-mediated knockdown of AUF1 inhibited prolonged hypersensitivity in females only, whereas overexpression of AUF1 in male DRG neurons increased pain-like responses. AUF1 knockdown was able to specifically inhibit repeated I/R-induced gene expression in females potentially downstream of prolactin receptor signaling. Data suggest RNA-binding proteins such as pAUF1 may underlie the sex-specific effects on DRG gene expression that modulates behavioral hypersensitivity after repeated I/R injury through prolactin signaling. This study may aid in finding distinct receptor differences related to the evolution of acute to chronic ischemic muscle pain development between sexes. (Copyright © 2024 International Association for the Study of Pain.)
Databáze:	MEDLINE
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