title: TMEM16F Regulates Spinal Microglial Function in Neuropathic Pain States.
abstract: 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 Ca(2+)-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.
authors.affiliation: EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy. Electronic address: batti@embl.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Batti
authors.affiliation: EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy.
authors.forename: Mayya
authors.initials: M
authors.lastname: Sundukova
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro, 5 00185 Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Murana
authors.affiliation: EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Pimpinella
authors.affiliation: EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy.
authors.forename: Fernanda
authors.initials: F
authors.lastname: De Castro Reis
authors.affiliation: Center for Life Nanoscience, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pagani
authors.affiliation: Pharmacology Institute, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro, 5 00185 Rome, Italy.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Pellegrino
authors.affiliation: EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy.
authors.forename: Emerald
authors.initials: E
authors.lastname: Perlas
authors.affiliation: Center for Life Nanoscience, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro, 5 00185 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Angelantonio
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro, 5 00185 Rome, Italy; IRCCS Neuromed, Via Atinese, Pozzilli 86077, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Ragozzino
authors.affiliation: EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy; Molecular Medicine Partnership Unit (MMPU), 69117 Heidelberg, Germany. Electronic address: paul.heppenstall@embl.it.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Heppenstall
mesh_terms: D000818:Animals; D000075368:Anoctamins; D002465:Cell Movement; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D008264:Macrophages / Q000378:metabolism; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology; D010587:Phagocytosis; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: C576687:ANO6 protein, mouse; D000075368:Anoctamins; D049294:Phospholipid Transfer Proteins