I am a
Home I AM A Search Login

Papers of the Week


Papers: 27 Mar 2021 - 2 Apr 2021


Animal Studies


2021 Mar 28


Free Radic Biol Med

Nox4-Dependent Upregulation of S100A4 after Peripheral Nerve Injury Modulates Neuropathic Pain Processing.

Authors

Wack G, Metzner K, Kuth MS, Wang E, Bresnick A, Brandes RP, Schröder K, Wittig I, Schmidtko A, Kallenborn-Gerhardt W
Free Radic Biol Med. 2021 Mar 28.
PMID: 33789124.

Abstract

Previous studies suggested that reactive oxygen species (ROS) produced by NADPH oxidase 4 (Nox4) affect the processing of neuropathic pain. However, mechanisms underlying Nox4-dependent pain signaling are incompletely understood. In this study, we aimed to identify novel Nox4 downstream interactors in the nociceptive system. Mice lacking Nox4 specifically in sensory neurons were generated by crossing Advillin-Cre mice with Nox4 mice. Tissue-specific deletion of Nox4 in sensory neurons considerably reduced mechanical hypersensitivity and neuronal action potential firing after peripheral nerve injury. Using a proteomic approach, we detected various proteins that are regulated in a Nox4-dependent manner after injury, including the small calcium-binding protein S100A4. Immunofluorescence staining and western blot experiments confirmed that S100A4 expression is massively up-regulated in peripheral nerves and dorsal root ganglia after injury. Furthermore, mice lacking S100A4 showed increased mechanical hypersensitivity after peripheral nerve injury and after delivery of a ROS donor. Our findings suggest that S100A4 expression is up-regulated after peripheral nerve injury in a Nox4-dependent manner and that deletion of S100A4 leads to an increased neuropathic pain hypersensitivity.