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Article

Electroacupuncture Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Rats via Suppressing TLR4 Signaling and TRPV1 Upregulation in Sensory Neurons

Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
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Int. J. Mol. Sci. 2019, 20(23), 5917; https://doi.org/10.3390/ijms20235917
Received: 15 October 2019 / Revised: 20 November 2019 / Accepted: 22 November 2019 / Published: 25 November 2019
(This article belongs to the Special Issue Capsaicin and TRPV1 in the Study of Pain and Organ Pathologies)
Paclitaxel-induced peripheral neuropathy is a common adverse effect during paclitaxel treatment resulting in sensory abnormalities and neuropathic pain during chemotherapy and in cancer survivors. Conventional therapies are usually ineffective and possess adverse effects. Here, we examined the effects of electroacupuncture (EA) on a rat model of paclitaxel-induced neuropathic pain and related mechanisms. EA robustly and persistently alleviated paclitaxel-induced pain hypersensitivities. Mechanistically, TLR4 (Toll-Like Receptor 4) and downstream signaling MyD88 (Myeloid Differentiation Primary Response 88) and TRPV1 (Transient Receptor Potential Vallinoid 1) were upregulated in dorsal root ganglion (DRGs) of paclitaxel-treated rats, whereas EA reduced their overexpression. Ca2+ imaging further indicated that TRPV1 channel activity was enhanced in DRG neurons of paclitaxel-treated rats whereas EA suppressed the enhanced TRPV1 channel activity. Pharmacological blocking of TRPV1 mimics the analgesic effects of EA on the pain hypersensitivities, whereas capsaicin reversed EA’s effect. Spinal astrocytes and microglia were activated in paclitaxel-treated rats, whereas EA reduced the activation. These results demonstrated that EA alleviates paclitaxel-induced peripheral neuropathic pain via mechanisms possibly involving suppressing TLR4 signaling and TRPV1 upregulation in DRG neurons, which further result in reduced spinal glia activation. Our work supports EA as a potential alternative therapy for paclitaxel-induced neuropathic pain. View Full-Text
Keywords: Paclitaxel; acupuncture; dorsal root ganglion; peripheral neuropathy; TRPV1; glial cell; TLR4 Paclitaxel; acupuncture; dorsal root ganglion; peripheral neuropathy; TRPV1; glial cell; TLR4
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MDPI and ACS Style

Li, Y.; Yin, C.; Li, X.; Liu, B.; Wang, J.; Zheng, X.; Shao, X.; Liang, Y.; Du, J.; Fang, J.; Liu, B. Electroacupuncture Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Rats via Suppressing TLR4 Signaling and TRPV1 Upregulation in Sensory Neurons. Int. J. Mol. Sci. 2019, 20, 5917. https://doi.org/10.3390/ijms20235917

AMA Style

Li Y, Yin C, Li X, Liu B, Wang J, Zheng X, Shao X, Liang Y, Du J, Fang J, Liu B. Electroacupuncture Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Rats via Suppressing TLR4 Signaling and TRPV1 Upregulation in Sensory Neurons. International Journal of Molecular Sciences. 2019; 20(23):5917. https://doi.org/10.3390/ijms20235917

Chicago/Turabian Style

Li, Yuanyuan, Chengyu Yin, Xiaojie Li, Boyu Liu, Jie Wang, Xiaoli Zheng, Xiaomei Shao, Yi Liang, Junying Du, Jianqiao Fang, and Boyi Liu. 2019. "Electroacupuncture Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Rats via Suppressing TLR4 Signaling and TRPV1 Upregulation in Sensory Neurons" International Journal of Molecular Sciences 20, no. 23: 5917. https://doi.org/10.3390/ijms20235917

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