Electroacupuncture Alleviates Spared Nerve Injury-Induced Neuropathic Pain And Modulates HMGB1/NF-κB Signaling Pathway In The Spinal Cord

• Main Authors: Xia Y, Xue M, Wang Y, Huang Z, Huang C
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-10-01
• Series: Journal of Pain Research
• Subjects: Electroacupunture; Neuropathic pain; Spared nerve injury; HMGB1/NF-κB signaling; TLR4
• Online Access: https://www.dovepress.com/electroacupuncture-alleviates-spared-nerve-injury-induced-neuropathic--peer-reviewed-article-JPR

Yang-yang Xia,1 Meng Xue,1 Ying Wang,1 Zhi-hua Huang,1,2 Cheng Huang1,2 1Department of Physiology, Gannan Medical University, Ganzhou 341000, People’s Republic of China; 2Pain Medicine Research Institute, Gannan Medical University, Ganzhou 341000, People’s Republic of ChinaCorrespondence: Cheng Huang; Zhi-hua HuangDepartment of Physiology, Gannan Medical University, Ganzhou 341000, People’s Republic of ChinaEmail [e-mail]; [e-mail]: Neuropathic pain with complications greatly affects patients worldwide. High mobility group box 1 (HMGB1) has been shown to contribute to the pathogenesis of neuropathic pain; thus, suppression of HMGB1 may provide a novel therapeutic option for neuropathic pain. Electroacupuncture (EA) has been indicated to be effective in attenuating neuropathic pain, but the underlying mechanism remains to be fully clarified. We aim to explore whether 2Hz EA stimulation regulates the spinal HMGB1/NF-κB signaling in neuropathic pain induced by spared nerve injury (SNI).Materials and methods: Paw withdrawal threshold and CatWalk gait analysis were used to assess the effect of 2Hz EA on pain-related behaviors in SNI rats. Administration of 2Hz EA to SNI rats once every other day lasting for 21 days. Expression of spinal protein molecules were detected using Western blot and immunofluorescence staining.Results: It was found that SNI significantly induced mechanical hypersensitivity and decrease of gait parameters, and subsequently increased the levels of HMGB1, TLR4, MyD88, and NF-κB p65 protein expression. 2Hz EA stimulation led to remarkable attenuation of mechanical hypersensitivity, upregulation of spinal HMGB1, TLR4, MyD88, and NF-κB p65 protein expressions induced by SNI, and significant improvement in gait parameters. Furthermore, immunofluorescence staining also confirmed that 2Hz EA obviously suppressed the co-expression of microglia activation marker CD11b and TLR4 or MyD88, as well as the activation of NF-κB p65 in SNI rats.Conclusion: This study suggested that blockade of HMGB1/NF-κB signaling in the spinal cord may be a promising therapeutic approach for 2Hz EA management of SNI-induced neuropathic pain.Keywords: electroacupuncture, neuropathic pain, spared nerve injury, HMGB1/NF-κB signaling, TLR4