I am a
Home I AM A Search Login

Papers of the Week

Papers: 1 Apr 2023 - 7 Apr 2023

Basic Science

Animal Studies, Molecular/Cellular, Neurobiology, Pharmacology/Drug Development


2023 Apr 05

Nat Commun




Editor's Pick

Role of TMEM100 in mechanically insensitive nociceptor un-silencing.


Nees TA, Wang N, Adamek P, Zeitzschel N, Verkest C, La Porta C, Schaefer I, Virnich J, Balkaya S, Prato V, Morelli C, Begay V, Lee YJ, Tappe-Theodor A, Lewin GR, Heppenstall PA, Taberner FJ, Lechner SG


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.