Neuroscience. 2024 May 1:S0306-4522(24)00174-X.doi: 10.1016/j.neuroscience.2024.04.015. Online ahead of print.

本文采用的英格恩产品: RNA-Entranster-invivo

Trim14-IκBα Signaling Regulates Chronic Inflammatory Pain in Rats and Osteoarthritis Patients

Affiliations

Affiliations

  • 1 Center for Translational Medicine, Department of Anesthesiology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China.
  • 2 Department of Pain, Suzhou Wuzhong People’s Hospital, Suzhou 215128, China.
  • 3 Center for Translational Medicine, Department of Anesthesiology, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215600, China. Electronic address: zhenhua_email@163.com.
  • 4 Center of Translational Medicine and Clinical Laboratory, The Fourth Affiliated Hospital of Soochow University, Medical Center of Soochow University, Suzhou Medical College of Soochow University, Suzhou 215123, China. Electronic address: hlzhang76@suda.edu.cn.

Free article

Abstract

Chronic inflammatory pain is the highest priority for people with osteoarthritis when seeking medical attention. Despite the availability of NSAIDs and glucocorticoids, central sensitization and peripheral sensitization make pain increasingly difficult to control. Previous studies have identified the ubiquitination system as an important role in the chronic inflammatory pain. Our study displayed that the E3 ubiquitin ligase tripartite motif-containing 14 (Trim14) was abnormally elevated in the serum of patients with osteoarthritis and pain, and the degree of pain was positively correlated with the degree of Trim14 elevation. Furthermore, CFA-induced inflammatory pain rat model showed that Trim14 was significantly increased in the L3-5 spinal dorsal horn (SDH) and dorsal root ganglion (DRG), and in turn the inhibitor of nuclear factor Kappa-B isoform α (IκBα) was decreased after Trim14 elevation. After intrathecal injection of Trim14 siRNA to inhibit Trim14 expression, IκBα expression was reversed and increased, and the pain behaviors and anxiety behaviors of rats were significantly relieved. Overall, these findings suggested that Trim14 may contribute to chronic inflammatory pain by degrading IκBα, and that Trim14 may become a novel therapeutic target for chronic inflammatory pain.

Keywords: IκBα; NF-κB; Trim14; chronic inflammatory pain; osteoarthritis.

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