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Role of TMEM100 in mechanically insensitive nociceptor un-silencing

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Item Type:Article
Title:Role of TMEM100 in mechanically insensitive nociceptor un-silencing
Creators Name:Nees, T.A. and Wang, N. and Adamek, P. and Zeitzschel, N. and Verkest, C. and La Porta, C. and Schaefer, I. and Virnich, J. and Balkaya, S. and Prato, V. and Morelli, C. and Begay, V. and Lee, Y.J. and Tappe-Theodor, A. and Lewin, G.R. and Heppenstall, P.A. and Taberner, F.J. and Lechner, S.G.
Abstract:Mechanically silent nociceptors are sensory afferents that are insensitive to noxious mechanical stimuli under normal conditions but become sensitized to such stimuli during inflammation. Using RNA-sequencing and quantitative RT-PCR we demonstrate that inflammation upregulates the expression of the transmembrane protein TMEM100 in silent nociceptors and electrophysiology revealed that over-expression of TMEM100 is required and sufficient to un-silence silent nociceptors in mice. Moreover, we show that mice lacking TMEM100 do not develop secondary mechanical hypersensitivity-i.e., pain hypersensitivity that spreads beyond the site of inflammation-during knee joint inflammation and that AAV-mediated overexpression of TMEM100 in articular afferents in the absence of inflammation is sufficient to induce mechanical hypersensitivity in remote skin regions without causing knee joint pain. Thus, our work identifies TMEM100 as a key regulator of silent nociceptor un-silencing and reveals a physiological role for this hitherto enigmatic afferent subclass in triggering spatially remote secondary mechanical hypersensitivity during inflammation.
Keywords:Chronic Pain, Neuronal Physiology, Somatic System, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:1899
Date:5 April 2023
Official Publication:https://doi.org/10.1038/s41467-023-37602-w
PubMed:View item in PubMed

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