Analgesic effects of electroacupuncture via the EphBs-p38 MAPK signaling pathway and microglial suppression in the chronic constriction injury rat model of neuropathic pain.

IF 2.6 3区 医学 Q2 INTEGRATIVE & COMPLEMENTARY MEDICINE
Yi Ying, Guodong Yang, Xiaoyu Li, Feifei Wang, Guobing Zhang
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引用次数: 0

Abstract

Objective: To explore the analgesic effects of electroacupuncture (EA) and its impact on the EphBs-p38 mitogen-activated protein kinase (MAPK) pathway and microglia in a rat model of neuropathic pain (NP).

Methods: Following adaptive training, 60 male Sprague Dawley (SD) rats were allocated to one of two experiments. In experiment 1, rats received intrathecal SB203580 (p38 MAPK inhibitor), intramuscular EphB1-Fc (EphBs inhibitor) or no injection before undergoing chronic constrictive injury (CCI). In experiment 2, CCI model rats received EA either alone or combined with either anisomycin (p38 MAPK agonist) or EphrinB1-Fc (EphBs agonist) versus minimal acupuncture (MA) as a control intervention. A sham surgery group was included in both experiments as a control for CCI. All groups consisted of n = 6 rats (four in experiment 1 and six in experiment 2). Behavioral hyperalgesia was examined and the spinal L5-6 region was harvested and subjected to enzyme-linked immunosorbent assay to assess tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels. Western blotting and immunofluorescence were used to assess protein expression of B-cell lymphoma (Bcl)-2, Bcl-2 associated X-protein (BAX), EphB1, EphrinB1, p38 MAPK, phosphorylated (p)-p38 MAPK and ionized calcium binding adaptor molecule (Iba)-1.

Results: CCI induced behavioral hyperalgesia, as demonstrated by altered paw withdrawal latency (PWL), paw withdrawal threshold (PWT) and cytokine levels, and increased p38 MAPK phosphorylation and microglial activation. However, inhibitors SB203580 and EphB1-Fc reversed these effects. Notably, EA showed similar beneficial effects, but these were counteracted when combined with anisomycin and EphrinB1-Fc.

Conclusions: The analgesic effects of EA in this rat model of NP appear to be linked to diminished p-p38 MAPK expression and subsequent microglial deactivation. EA has a potential role as a complementary therapy for NP.

电针通过EphBs-p38 MAPK信号通路和小胶质细胞抑制对慢性收缩损伤大鼠神经性疼痛模型的镇痛作用
目的:探讨电针(EA)在神经性疼痛(NP)大鼠模型中的镇痛作用及其对EphBs-p38丝裂原活化蛋白激酶(MAPK)通路和小胶质细胞的影响。方法:选取60只雄性SD大鼠进行适应性训练,随机分为两组。在实验1中,大鼠在慢性收缩性损伤(CCI)前接受鞘内注射SB203580 (p38 MAPK抑制剂)、肌内注射EphB1-Fc (EphBs抑制剂)或不注射。在实验2中,CCI模型大鼠接受EA单独或联合大霉素(p38 MAPK激动剂)或EphrinB1-Fc (EphBs激动剂),而不是最小针灸(MA)作为对照干预。两个实验均设假手术组作为CCI的对照组。每组n = 6只大鼠(实验1 4只,实验2 6只)。检查行为痛觉过敏,收集脊髓L5-6区域,并进行酶联免疫吸附试验以评估肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β水平。采用Western blotting和免疫荧光法检测b细胞淋巴瘤(Bcl)-2、Bcl-2相关x蛋白(BAX)、EphB1、EphrinB1、p38 MAPK、磷酸化(p)-p38 MAPK和离子化钙结合接头分子(Iba)-1的蛋白表达。结果:CCI诱导了行为性痛觉过敏,其表现为足部戒断潜伏期(PWL)、足部戒断阈值(PWT)和细胞因子水平的改变,以及p38 MAPK磷酸化和小胶质细胞活化的增加。然而,抑制剂SB203580和EphB1-Fc逆转了这些作用。值得注意的是,EA显示出类似的有益作用,但当与大霉素和EphrinB1-Fc联合使用时,这些作用被抵消。结论:EA在NP大鼠模型中的镇痛作用似乎与p-p38 MAPK表达降低和随后的小胶质细胞失活有关。EA有可能作为NP的补充疗法。
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来源期刊
Acupuncture in Medicine
Acupuncture in Medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-
CiteScore
4.70
自引率
4.00%
发文量
59
审稿时长
6-12 weeks
期刊介绍: Acupuncture in Medicine aims to promote the scientific understanding of acupuncture and related treatments by publishing scientific investigations of their effectiveness and modes of action as well as articles on their use in health services and clinical practice. Acupuncture in Medicine uses the Western understanding of neurophysiology and anatomy to interpret the effects of acupuncture.
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