TMEM16F Regulates Spinal Microglial Function in Neuropathic Pain States
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
Affiliations
Laura Batti
EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy
Mayya Sundukova
EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy
Emanuele Murana
Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro, 5 00185 Rome, Italy
Sofia Pimpinella
EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy
Fernanda De Castro Reis
EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy
Francesca Pagani
Center for Life Nanoscience, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy
Hong Wang
Pharmacology Institute, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg
Eloisa Pellegrino
Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro, 5 00185 Rome, Italy
Emerald Perlas
EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy
Silvia Di Angelantonio
Center for Life Nanoscience, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy
Davide Ragozzino
Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro, 5 00185 Rome, Italy
Paul A. Heppenstall
EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy
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.
