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在大鼠慢性疼痛损伤模型中,高压氧可能通过Kindlin-1/Wnt-10a信号通路减轻神经性疼痛并逆转炎症信号。

Hyperbaric oxygen attenuates neuropathic pain and reverses inflammatory signaling likely via the Kindlin-1/Wnt-10a signaling pathway in the chronic pain injury model in rats.

作者信息

Zhao Baisong, Pan Yongying, Xu Haiping, Song Xingrong

机构信息

Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Tianhe District, Guangzhou, Guangdong, 510623, China.

出版信息

J Headache Pain. 2017 Dec;18(1):1. doi: 10.1186/s10194-016-0713-y. Epub 2017 Jan 5.

DOI:10.1186/s10194-016-0713-y
PMID:28058534
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5216011/
Abstract

BACKGROUND

Hyperbaric oxygen (HBO) therapy is proven to attenuate neuropathic pain in rodents. The goal of the present study was to determine the potential involvement of the Kindlin-1/Wnt-10a signaling pathway during astrocyte activation and inflammation in a rodent model of neuropathic pain.

METHODS

Rats were assigned into sham operation, chronic constriction injury (CCI), and CCI + HBO treatment groups. Neuropathic pain developed in rats following CCI of the sciatic nerve. Rats in the CCI + HBO group received HBO treatment for five consecutive days beginning on postoperative day 1. The mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) tests were performed to determine mechanical and heat hypersensitivity of animals, respectively. Kindlin-1, Wnt-10a and β-catenin protein expression was examined by immunohistochemistry and Western blot analysis. Expression of tumor necrosis factor (TNF)-α was also determined by ELISA.

RESULTS

Our findings demonstrated that HBO treatment significantly suppressed mechanical and thermal hypersensitivity in the CCI neuropathic pain model in rats. HBO therapy significantly reversed the up-regulation of Kindlin-1 in dorsal root ganglia (DRG), spinal cord, and hippocampus of CCI rats. CCI-induced astrocyte activation and increased levels of TNF-α were efficiently reversed by HBO (P < 0.05 vs. CCI). HBO also reversed Wnt-10a up-regulation induced by CCI in the DRG, spinal cord, and hippocampus (P < 0.05 vs. CCI).

CONCLUSIONS

Our findings demonstrate that HBO attenuated CCI-induced rat neuropathic pain and inflammatory responses, possibly through regulation of the Kindlin-1/Wnt-10a signaling pathway.

摘要

背景

高压氧(HBO)疗法已被证明可减轻啮齿动物的神经性疼痛。本研究的目的是确定在神经性疼痛的啮齿动物模型中,Kindlin-1/Wnt-10a信号通路在星形胶质细胞激活和炎症过程中的潜在作用。

方法

将大鼠分为假手术组、慢性缩窄损伤(CCI)组和CCI + HBO治疗组。坐骨神经CCI后大鼠出现神经性疼痛。CCI + HBO组大鼠从术后第1天开始连续5天接受HBO治疗。分别进行机械性撤离阈值(MWT)和热撤离潜伏期(TWL)测试,以确定动物的机械性和热超敏反应。通过免疫组织化学和蛋白质印迹分析检测Kindlin-1、Wnt-10a和β-连环蛋白的蛋白表达。还通过酶联免疫吸附测定(ELISA)法测定肿瘤坏死因子(TNF)-α的表达。

结果

我们的研究结果表明,HBO治疗可显著抑制CCI大鼠神经性疼痛模型中的机械性和热超敏反应。HBO疗法显著逆转了CCI大鼠背根神经节(DRG)、脊髓和海马中Kindlin-1的上调。HBO有效逆转了CCI诱导的星形胶质细胞激活和TNF-α水平升高(与CCI组相比,P < 0.05)。HBO还逆转了CCI在DRG、脊髓和海马中诱导的Wnt-10a上调(与CCI组相比,P < 0.05)。

结论

我们的研究结果表明,HBO可能通过调节Kindlin-1/Wnt-10a信号通路减轻CCI诱导的大鼠神经性疼痛和炎症反应。

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