TMEM16F regulates spinal microglial function in neuropathic pain states

Neuropathic pain is a widespread chronic pain state that results from injury to the nervous system. Spinal microglia play a causative role in the pathogenesis of neuropathic pain through secretion of growth factors and cytokines. Here, we investigated the contribution of TMEM16F, a protein that func...

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Main Authors: Batti, Laura (Author) , Sundukova, Mayya (Author) , Murana, Emanuele (Author) , Pimpinella, Sofia (Author) , De Castro Reis, Fernanda (Author) , Pagani, Francesca (Author) , Wang, Hong (Author) , Pellegrino, Eloisa (Author) , Perlas, Emerald (Author) , Di Angelantonio, Silvia (Author) , Ragozzino, Davide (Author) , Heppenstall, Paul A. (Author)
Format: Article (Journal)
Language:English
Published: 21 June 2016
In: Cell reports
Year: 2016, Volume: 15, Issue: 12, Pages: 2608-2615
ISSN:2211-1247
DOI:10.1016/j.celrep.2016.05.039
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2016.05.039
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S2211124716306222
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Author Notes:Laura Batti, Mayya Sundukova, Emanuele Murana, Sofia Pimpinella, Fernanda De Castro Reis, Francesca Pagani, Hong Wang, Eloisa Pellegrino, Emerald Perlas, Silvia Di Angelantonio, Davide Ragozzino, Paul A. Heppenstall
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Summary:Neuropathic pain is a widespread chronic pain state that results from injury to the nervous system. Spinal microglia play a causative role in the pathogenesis of neuropathic pain through secretion of growth factors and cytokines. Here, we investigated the contribution of TMEM16F, a protein that functions as a Ca2+-dependent ion channel and a phospholipid scramblase, to microglial activity during neuropathic pain. We demonstrate that mice with a conditional ablation of TMEM16F in microglia do not develop mechanical hypersensitivity upon nerve injury. In the absence of TMEM16F, microglia display deficits in process motility and phagocytosis. Moreover, loss of GABA immunoreactivity upon injury is spared in TMEM16F conditional knockout mice. Collectively, these data indicate that TMEM16F is an essential component of the microglial response to injury and suggest the importance of microglial phagocytosis in the pathogenesis of neuropathic pain.
Item Description:Gesehen am 23.04.2020
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2016.05.039