Electroacupuncture alleviates paclitaxel-induced peripheral neuropathy by reducing CCL2-mediated macrophage infiltration in sensory ganglia and sciatic nerve
Abstract Background 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 a...
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BMC
2025-01-01
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| Series: | Chinese Medicine |
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| Online Access: | https://doi.org/10.1186/s13020-024-01023-8 |
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| author | Yuanyuan Li Ruoyao Xu Muyan Chen Kaige Zheng Huimin Nie Chengyu Yin Boyu Liu Yan Tai Junying Du Jie Wang Jianqiao Fang Boyi Liu |
| author_facet | Yuanyuan Li Ruoyao Xu Muyan Chen Kaige Zheng Huimin Nie Chengyu Yin Boyu Liu Yan Tai Junying Du Jie Wang Jianqiao Fang Boyi Liu |
| author_sort | Yuanyuan Li |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| format | Article |
| id | doaj-art-539e45f833f548038cacc829bec15582 |
| institution | Kabale University |
| issn | 1749-8546 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj-art-539e45f833f548038cacc829bec155822025-01-19T12:38:44ZengBMCChinese Medicine1749-85462025-01-0120111810.1186/s13020-024-01023-8Electroacupuncture alleviates paclitaxel-induced peripheral neuropathy by reducing CCL2-mediated macrophage infiltration in sensory ganglia and sciatic nerveYuanyuan Li0Ruoyao Xu1Muyan Chen2Kaige Zheng3Huimin Nie4Chengyu Yin5Boyu Liu6Yan Tai7Junying Du8Jie Wang9Jianqiao Fang10Boyi Liu11Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical UniversityDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical UniversityDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical UniversityDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical UniversityDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical UniversityDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical UniversityDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical UniversityAcademy of Chinese Medical Sciences, Zhejiang Chinese Medical UniversityDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical UniversityDepartment of Rehabilitation in Traditional Chinese Medicine, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical UniversityDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Zhejiang Chinese Medical UniversityAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s13020-024-01023-8PaclitaxelChemotherapyNeuropathyMacrophagesAcupuncturePain |
| spellingShingle | Yuanyuan Li Ruoyao Xu Muyan Chen Kaige Zheng Huimin Nie Chengyu Yin Boyu Liu Yan Tai Junying Du Jie Wang Jianqiao Fang Boyi Liu Electroacupuncture alleviates paclitaxel-induced peripheral neuropathy by reducing CCL2-mediated macrophage infiltration in sensory ganglia and sciatic nerve Chinese Medicine Paclitaxel Chemotherapy Neuropathy Macrophages Acupuncture Pain |
| title | Electroacupuncture alleviates paclitaxel-induced peripheral neuropathy by reducing CCL2-mediated macrophage infiltration in sensory ganglia and sciatic nerve |
| title_full | Electroacupuncture alleviates paclitaxel-induced peripheral neuropathy by reducing CCL2-mediated macrophage infiltration in sensory ganglia and sciatic nerve |
| title_fullStr | Electroacupuncture alleviates paclitaxel-induced peripheral neuropathy by reducing CCL2-mediated macrophage infiltration in sensory ganglia and sciatic nerve |
| title_full_unstemmed | Electroacupuncture alleviates paclitaxel-induced peripheral neuropathy by reducing CCL2-mediated macrophage infiltration in sensory ganglia and sciatic nerve |
| title_short | Electroacupuncture alleviates paclitaxel-induced peripheral neuropathy by reducing CCL2-mediated macrophage infiltration in sensory ganglia and sciatic nerve |
| title_sort | electroacupuncture alleviates paclitaxel induced peripheral neuropathy by reducing ccl2 mediated macrophage infiltration in sensory ganglia and sciatic nerve |
| topic | Paclitaxel Chemotherapy Neuropathy Macrophages Acupuncture Pain |
| url | https://doi.org/10.1186/s13020-024-01023-8 |
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