BACKGROUND Peripheral nerve injury causes limb muscle/bone atrophy, leading to chronic pain. However, the mechanisms underlying muscle/bone atrophy after peripheral nerve injury remain unknown. It was recently reported that M1 macrophages are the main factors responsible for neurogenic inflammation after peripheral nerve injury. We hypothesized that M1 macrophages are important in muscle/bone atrophy after nerve injury. Therefore, we investigated the influence of M1 macrophages on muscle/bone atrophy after nerve injury in mice to prevent muscle/bone atrophy by suppressing M1 macrophages. METHODS Hindlimb muscle weight and total bone density were measured in a chronic constriction injury (CCI) mouse model. Immunohistochemical analysis and intravital microscopy were performed to visualize hindlimb muscles/bones, and cells were quantified using flow cytometry. We compared M1 macrophage infiltration into muscles/bones and muscle/bone atrophy between macrophage depletion and untreated groups. We also investigated muscle/bone atrophy using administration models for anti-inflammatory and neuropathic pain drugs. RESULTS Peripheral nerve injury caused significant reduction in muscle weight and total bone density at 1 and 3 weeks after CCI, respectively, compared with that in controls. Osteoclast numbers were significantly higher at 1 week after CCI in the CCI group than in the control group. M1 macrophage infiltration into muscles was observed from 2 h after CCI via intravital microscopy and 1 week after CCI, and it was significantly higher 1 week after CCI than in the control group. In the macrophage depletion group, dexamethasone, pregabalin, and loxoprofen groups, M1 macrophage infiltration into muscles/bones was significantly lower and muscle weight and total bone density were significantly higher than in the untreated group. CONCLUSIONS M1 macrophage infiltration exacerbates muscle/bone atrophy after peripheral nerve injury. By suppressing M1 macrophages at the neural injury local site, muscle/bone atrophy could be avoided.

中文翻译：

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周围神经损伤后，M1巨噬细胞浸润加剧了肌肉/骨骼萎缩。

背景技术周围神经损伤导致肢体肌肉/骨骼萎缩，从而导致慢性疼痛。然而，周围神经损伤后肌肉/骨骼萎缩的潜在机制仍然未知。最近有报道说，M1巨噬细胞是造成周围神经损伤后神经性炎症的主要因素。我们假设M1巨噬细胞在神经损伤后的肌肉/骨骼萎缩中很重要。因此，我们调查了M1巨噬细胞对小鼠神经损伤后肌肉/骨骼萎缩的影响，以通过抑制M1巨噬细胞来预防肌肉/骨骼萎缩。方法在慢性收缩损伤（CCI）小鼠模型中测量后肢肌肉重量和总骨密度。进行了免疫组织化学分析和活体显微镜检查以可视化后肢肌肉/骨骼，并且使用流式细胞仪对细胞进行定量。我们比较了巨噬细胞耗竭组和未治疗组之间M1巨噬细胞浸润到肌肉/骨骼和肌肉/骨骼萎缩的情况。我们还使用抗炎和神经性止痛药的给药模型研究了肌肉/骨骼萎缩。结果与对照组相比，在CCI后1周和3周时，周围神经损伤分别导致肌肉重量和总骨密度显着降低。CCI组在第1周时破骨细胞的数量显着高于对照组。从CCI后2小时通过活体显微镜观察到C1后1周，观察到M1巨噬细胞向肌肉的浸润，并且CCI后1周比对照组明显更高。在巨噬细胞耗竭组中，地塞米松，普瑞巴林，与洛索洛芬组相比，未治疗组的M1巨噬细胞向肌肉/骨骼的浸润明显降低，肌肉重量和总骨密度明显升高。结论M1巨噬细胞浸润加剧了周围神经损伤后的肌肉/骨骼萎缩。通过抑制神经损伤部位的M1巨噬细胞，可以避免肌肉/骨骼萎缩。