电针通过EphBs-p38丝裂原活化蛋白激酶信号通路及抑制小胶质细胞发挥镇痛作用在神经性疼痛慢性缩窄性损伤大鼠模型中的研究

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

作者信息

Ying Yi, Yang Guodong, Li Xiaoyu, Wang Feifei, Zhang Guobing

机构信息

Department of Traditional Chinese Medicine, XianJu People's Hospital, Zhejiang Southeast Campus of Zhejiang Provincial People's Hospital, Affiliated Xianju's Hospital, Hangzhou Medical College, Taizhou, China.

Department of Orthopedics, XianJu People's Hospital, Zhejiang Southeast Campus of Zhejiang Provincial People's Hospital, Affiliated Xianju's Hospital, Hangzhou Medical College, Taizhou, China.

出版信息

Acupunct Med. 2025 Aug 23:9645284251363987. doi: 10.1177/09645284251363987.

DOI:10.1177/09645284251363987

PMID:40847801

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.

摘要

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

适应性训练后，将60只雄性Sprague Dawley（SD）大鼠分配到两个实验之一。在实验1中，大鼠在接受慢性缩窄性损伤（CCI）之前接受鞘内注射SB203580（p38 MAPK抑制剂）、肌肉注射EphB1-Fc（EphBs抑制剂）或不注射。在实验2中，CCI模型大鼠接受单独的EA或与茴香霉素（p38 MAPK激动剂）或EphrinB1-Fc（EphBs激动剂）联合使用，与最小针刺（MA）作为对照干预。两个实验均包括假手术组作为CCI的对照。所有组均由n = 6只大鼠组成（实验1中为4只，实验2中为6只）。检测行为性痛觉过敏，并采集脊髓L5-6区域，进行酶联免疫吸附测定以评估肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β水平。采用蛋白质免疫印迹法和免疫荧光法评估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和离子钙结合衔接分子（Iba）-1的蛋白表达。

结果

CCI诱导行为性痛觉过敏，表现为爪部撤离潜伏期（PWL）、爪部撤离阈值（PWT）和细胞因子水平改变，p38 MAPK磷酸化增加和小胶质细胞活化。然而，抑制剂SB203580和EphB1-Fc可逆转这些效应。值得注意的是，EA显示出类似的有益效果，但与茴香霉素和EphrinB1-Fc联合使用时这些效果被抵消。