Peripheral nerve injury-induced mechanical allodynia is often accompanied by abnormalities in the higher cortical regions, yet the mechanisms underlying such maladaptive cortical plasticity remain unclear. Here, we show that in male mice, structural and functional changes in the primary somatosensory cortex (S1) caused by peripheral nerve injury require neuron-microglial signaling within the local circuit. Following peripheral nerve injury, microglia in the S1 maintain ramified morphology and normal density but up-regulate the mRNA expression of brain-derived neurotrophic factor (BDNF). Using in vivo two-photon imaging and Cx3cr1CreER;Bdnfflox mice, we show that conditional knockout of BDNF from microglia prevents nerve injury-induced synaptic remodeling and pyramidal neuron hyperactivity in the S1, as well as pain hypersensitivity in mice. Importantly, S1-targeted removal of microglial BDNF largely recapitulates the beneficial effects of systemic BDNF depletion on cortical plasticity and allodynia. Together, these findings reveal a pivotal role of cerebral microglial BDNF in somatosensory cortical plasticity and pain hypersensitivity.

中文翻译：

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脑小胶质细胞产生的 BDNF 促进外周神经损伤后的皮质可塑性和疼痛超敏反应。

外周神经损伤引起的机械性异常性疼痛通常伴有较高皮层区域的异常，但这种适应不良的皮层可塑性的机制仍不清楚。在这里，我们表明，在雄性小鼠中，由周围神经损伤引起的初级体感皮层 (S1) 的结构和功能变化需要局部回路内的神经元-小胶质细胞信号传导。周围神经损伤后，S1 中的小胶质细胞保持分枝形态和正常密度，但上调脑源性神经营养因子 (BDNF) 的 mRNA 表达。使用体内双光子成像和 Cx3cr1CreER；Bdnfflox 小鼠，我们表明有条件地敲除小胶质细胞中的 BDNF 可以防止 S1 中神经损伤诱导的突触重塑和锥体神经元过度活跃，以及小鼠的疼痛超敏反应。重要的是，S1 靶向去除小胶质细胞 BDNF 在很大程度上概括了全身 BDNF 消耗对皮质可塑性和异常性疼痛的有益影响。总之，这些发现揭示了大脑小胶质细胞 BDNF 在躯体感觉皮层可塑性和疼痛超敏反应中的关键作用。