Dexmedetomidine Alleviates CCI-Induced Neuropathic Pain via Inhibiting HMGB1-Mediated Astrocyte Activation and the TLR4/
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ORIGINAL ARTICLE
Dexmedetomidine Alleviates CCI-Induced Neuropathic Pain via Inhibiting HMGB1-Mediated Astrocyte Activation and the TLR4/NF-κB Signaling Pathway in Rats Erxian Zhao 1 & Liying Bai 1 & Shurong Li 2 & Li Li 1 & Zhongci Dou 1 & Yunli Huang 1 & Yan Li 1 & Yunqi Lv 1 Received: 7 April 2020 / Revised: 21 May 2020 / Accepted: 17 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract To investigate the effects of dexmedetomidine on chronic constriction injury (CCI)–induced neuropathic pain and to further explore its mechanism. A CCI rat model was established and treatment with dexmedetomidine. The paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were monitored at different time points, and the effects of hematoxylin-eosin staining on the sciatic nerve morphology of rats were observed. Immunohistochemical and immunofluorescence analyses were used to detect the expression of high mobility group box-1 (HMGB1) protein and glial fibrillary acidic protein (GFAP), and protein fluorescence intensity of GFAP in spinal cord tissue, respectively. Moreover, the expression of HMGB1 and Toll-like receptor-4/nuclear factor kappa-B (TLR4/NF-κB) pathway–related proteins were detected by western blot assay. To verify whether dexmedetomidine alleviates CCI-induced neuropathic pain by inhibiting HMGB1-mediated astrocyte activation and the TLR4/NF-κB signaling pathway, the rats were further treated with an HMGB1 activator or antagonist. Dexmedetomidine was found to improve the pathological changes of the sciatic nerve and alleviate pain in the CCI rats. The expression of HMGB1, GFAP, TLR4, TRAF6, MyD88, and p-P65 were greatly downregulated in the spinal cord tissues of the CCI rats. In addition, a further study showed that an HMGB1 activator can reverse the inhibition of neuropathic pain behaviors of dexmedetomidine. Overexpression of HMGB1 downregulated the PWMT and PWTL and enhanced the astrocyte activity and the TLR4/NF-κB signaling pathway in CCI rats. These results indicated that dexmedetomidine can alleviate neuropathic pain in CCI rats by inhibiting HMGB1-mediated astrocyte activation and the TLR4/NF-κB signaling pathway. Keywords Dexmedetomidine . Chronic constriction injury (CCI) . HMGB1 . Astrocyte . TLR4/NF-κB
Introduction Neuropathic pain is a chronic pain condition caused by a lesion or diseases affecting the somatosensory system (Popiolekbarczyk and Mika 2016). The pathogenesis of neuropathic pain is complex and the clinical treatment effect is Erxian Zhao and Liying Bai contributed equally to this work. Significance Dexmedetomidine may be used to treat neuropathic pain. * Yunqi Lv [email protected] 1
Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan Province, China
2
Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100000, China
not good. Although spinal neuronal dysfunction plays an i
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