Batti Laura, Sundukova Mayya, Murana Emanuele, Pimpinella Sofia, De Castro Reis Fernanda, Pagani Francesca, Wang Hong, Pellegrino Eloisa, Perlas Emerald, Di Angelantonio Silvia, Ragozzino Davide, Heppenstall Paul A
EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy.
EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy.
Cell Rep. 2016 Jun 21;15(12):2608-15. doi: 10.1016/j.celrep.2016.05.039.
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.
神经性疼痛是一种广泛存在的慢性疼痛状态，由神经系统损伤引起。脊髓小胶质细胞通过分泌生长因子和细胞因子在神经性疼痛的发病机制中起致病作用。在此，我们研究了作为Ca(2+)依赖性离子通道和磷脂翻转酶发挥作用的蛋白质TMEM16F在神经性疼痛期间对小胶质细胞活性的贡献。我们证明，小胶质细胞中TMEM16F条件性缺失的小鼠在神经损伤后不会出现机械性超敏反应。在没有TMEM16F的情况下，小胶质细胞在突起运动和吞噬作用方面表现出缺陷。此外，TMEM16F条件性敲除小鼠损伤后GABA免疫反应性的丧失得以幸免。总的来说，这些数据表明TMEM16F是小胶质细胞对损伤反应的重要组成部分，并提示小胶质细胞吞噬作用在神经性疼痛发病机制中的重要性。
