Li Yuanyuan, Xu Ruoyao, Chen Muyan, Zheng Kaige, Nie Huimin, Yin Chengyu, Liu Boyu, Tai Yan, Du Junying, Wang Jie, Fang Jianqiao, Liu Boyi
Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, China.
Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Chin Med. 2025 Jan 13;20(1):9. doi: 10.1186/s13020-024-01023-8.
Paclitaxel-induced peripheral neuropathy (PIPN) is prevalent among patients receiving paclitaxel chemotherapy, which results in sensory abnormality as well as neuropathic pain. Conventional medications lack effectiveness on PIPN. Clinical trials identified beneficial effects of acupuncture on PIPN among patients receiving chemotherapy. Here we explored the mechanisms underlying how acupuncture might alleviate PIPN.
A mouse model of PIPN was established by repeated paclitaxel application. Electroacupuncture (EA) was applied at ST36 and BL60 acupoints of model mice. Immunostaining, flow cytometry, behavioral assay, in vivo imaging were utilized for effects determination and mechanism exploration.
EA ameliorated mechanical and cold pain hypersensitivities, reduced sensory neuron damage and improved loss in intra-epidermal nerve fibers (IENFs) in model mice. Macrophages infiltration were detected in DRG and sciatic nerve of model mice, which was reduced by EA. EA affected M1-like pro-inflammatory macrophage infiltration in DRG, whereas it did not affect M2-like macrophages. DRG neurons released chemoattractant CCL2 that recruited macrophages via CCR2 to DRG. EA reduced CCL2 overproduction by DRG neurons and reduced macrophage infiltration. Blocking CCR2 mimicked EA's anti-allodynic effect, whereas exogenously applying recombinant CCL2 reversed the ameliorative effect of EA on macrophage infiltration and abolished EA's anti-allodynia on model mice. EA ameliorated other signs of PIPN, including sensory neuron damage, sciatic nerve morphology impairment and IENFs loss. In mice inoculated with breast cancer cells, EA didn't affect paclitaxel-induced antitumor effect.
These findings suggest EA alleviates PIPN by reducing CCL2/CCR2 mediated-pro-inflammatory macrophage infiltration into sensory ganglia as well as the sciatic nerve. Our study supports EA could be used as a potential non-pharmacological therapy for PIPN.
紫杉醇引起的周围神经病变（PIPN）在接受紫杉醇化疗的患者中很常见，会导致感觉异常以及神经性疼痛。传统药物对PIPN缺乏疗效。临床试验证实针灸对接受化疗的患者的PIPN有有益作用。在此我们探究了针灸可能缓解PIPN的潜在机制。
通过重复应用紫杉醇建立PIPN小鼠模型。对模型小鼠的足三里（ST36）和昆仑（BL60）穴位进行电针治疗。利用免疫染色、流式细胞术、行为学检测、体内成像来确定疗效并探索机制。
电针改善了模型小鼠的机械性和冷痛超敏反应，减少了感觉神经元损伤，并改善了表皮内神经纤维（IENF）的缺失。在模型小鼠的背根神经节（DRG）和坐骨神经中检测到巨噬细胞浸润，电针可使其减少。电针影响DRG中M1样促炎性巨噬细胞浸润，但不影响M2样巨噬细胞。DRG神经元释放趋化因子CCL2，通过CCR2将巨噬细胞募集到DRG。电针减少了DRG神经元CCL2的过量产生并减少了巨噬细胞浸润。阻断CCR2模拟了电针的抗痛觉过敏作用，而外源性应用重组CCL2则逆转了电针对巨噬细胞浸润的改善作用，并消除了电针在模型小鼠上的抗痛觉过敏作用。电针改善了PIPN的其他症状，包括感觉神经元损伤、坐骨神经形态损伤和IENF缺失。在接种乳腺癌细胞的小鼠中，电针不影响紫杉醇诱导的抗肿瘤作用。
这些发现表明，电针通过减少CCL2/CCR2介导的促炎性巨噬细胞浸润到感觉神经节以及坐骨神经中来缓解PIPN。我们的研究支持电针可作为PIPN的一种潜在非药物治疗方法。
