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TMEM16F Regulates Spinal Microglial Function in Neuropathic Pain States
Laura Batti1, Mayya Sundukova1, Emanuele Murana2
1EMBL Mouse Biology Unit, Via Ramarini 32, Monterotondo 00015, Italy.
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.
Insights
TMEM16F protein in spinal microglia is crucial for neuropathic pain development. Its absence prevents pain hypersensitivity by impairing microglial function and phagocytosis.
Area of Science:
- Neuroscience
- Immunology
Background:
- Neuropathic pain is a chronic pain state caused by nervous system injury.
- Spinal microglia contribute to neuropathic pain via growth factors and cytokines.
Purpose of the Study:
- Investigate the role of TMEM16F in microglial activity during neuropathic pain.
- Determine TMEM16F's function as a Ca(2+)-dependent ion channel and phospholipid scramblase in microglia.
Main Methods:
- Used conditional knockout mice lacking TMEM16F in microglia.
- Assessed mechanical hypersensitivity, microglial process motility, and phagocytosis post-nerve injury.
- Monitored GABA immunoreactivity changes.
Main Results:
- Mice lacking TMEM16F in microglia did not develop mechanical hypersensitivity.
- TMEM16F deficiency impaired microglial process motility and phagocytosis.
- Loss of GABA immunoreactivity was prevented in TMEM16F knockout mice.
Conclusions:
- TMEM16F is essential for the microglial response to nerve injury.
- Microglial phagocytosis mediated by TMEM16F is critical in neuropathic pain pathogenesis.
