Mechanism of alleviating neuropathic pain in rats by inhibiting the expression of P38MAPK signaling pathway

doi:10.3760/cma.j.issn.1007-1245.2024.10.016

Abstract

Abstract:

Objective　To explore the mechanism of alleviating neuropathic pain in rats by inhibiting the expression of P38 mitogen-activited protein kinase (P38MAPK) signaling pathway. Methods　Sixty male specific pathogen-free (SPF) grade rats were selected (body weight 200 - 220 g, about 3 months old), among them 10 rats were randomly selected as a sham operation group, and the remaining rats were used to establish a chronic compressive injury (CCI) model. The rat models [the success rate of modeling was 80% (40/50)] were randomly divided into a model group and a P38MAPK inhibitor group. On the 6th day after modeling, normal saline and P38MAPK inhibitor were injected into the sheath twice a day for consecutive 5 days. The mechanical pain threshold and motor function score of the rats in each group were measured 1, 7 and 11 days after operation. The rats were euthanized on the 11th day after operation, and the expressions of P38MAPK and cyclooxygenase-2 (COX-2) protein in the dorsal root ganglia of the rats were determined by the immunohistochemical method. The measurement data were analyzed by repeated measure ANOVA. Results　There was no significant change in the mechanical pain threshold in the sham operation group; the pain threshold level of the model group significantly decreased on the 7th day and to the lowest level on the 11th day after operation; the pain threshold level in the P38MAPK inhibitor group decreased on the 7th day and significantly increased on the 11th day after operation (P<0.05), which was higher than that in the model group (P<0.05). The model group and the P38MAPK inhibitor group showed significant motor dysfunction on the 7th day after operation; the degree of motor dysfunction in the model group increased on the 11th day, but the degree of motor dysfunction in the P38MAPK inhibitor group decreased on the 11th day (P<0.05), whose motor function score was lower than that of the model group (P<0.05). The expression of P38MAPK immune positive cells in the sham operation group was lower than that in the P38MAPK inhibitor group and lower than that in the model group [(7.35±0.63)% vs. (25.36±1.85)% vs. (60.23±2.17)%] (P<0.05); the expression of COX-2 protein-positive cells in the sham operation group was lower than that in the P38MAPK inhibitor group and lower than that in the model group [(5.21±2.23)% vs. (15.14±2.01)% vs. (33.43±3.02)%] (P<0.05). Conclusion　The P38MAPK signaling pathway is related to the occurrence of neuropathic pain, and inhibiting the expression of P38MAPK signaling pathway can alleviate neuropathic pain in rats.

Key words:

Neuropathic pain, P38MAPK signaling pathway, Animal experiment

摘要：

目的　探究抑制P38丝裂原活化蛋白激酶（P38MAPK）信号通路表达减轻大鼠神经病理性疼痛的机制。方法　选取60只雄性无特定病原体（SPF）级大鼠（体质量200～220 g，3月龄左右），随机抽取10只作为假手术组，其余大鼠建立大鼠慢性压迫性损伤（CCI）模型。将成模大鼠［造模成功率为80%（40/50）］随机分为模型组、P38MAPK抑制剂组，造模后第6天分别鞘内注射生理盐水、P38MAPK抑制剂，2次/d，连续5 d。术后1、7、11 d测定各组大鼠机械性痛阈、运动功能评分。术后第11天处死大鼠，采用免疫组化法测定大鼠背根神经节P38MAPK、环氧合酶-2（COX-2）蛋白表达。计量资料采用重复测量方差分析。结果　假手术组大鼠机械性痛阈变化不明显；模型组大鼠第7天开始痛阈水平降低，至第11天降至最低；P38MAPK抑制剂组第7天痛阈水平降低，第11天升高（P<0.05），且高于模型组（P<0.05）；模型组与P38MAPK抑制剂组在第7天出现明显运动功能障碍，第11天模型组运动功能障碍程度增加，第11天P38MAPK抑制剂组运动功能障碍程度减轻（P<0.05），且运动功能评分低于模型组（P<0.05）；假手术组P38MAPK免疫阳性细胞表达<P38MAPK抑制剂组<模型组［（7.35±0.63）%比（25.36±1.85）%比（60.23±2.17）%］（P<0.05）；假手术组COX-2蛋白阳性细胞表达<P38MAPK抑制剂组<模型组［（5.21±2.23）%比（15.14±2.01）%比（33.43±3.02）%］（P<0.05）。结论　P38MAPK信号通路与神经病理性疼痛发生有关，抑制P38MAPK信号通路表达可减轻大鼠神经病理性疼痛。

关键词:

神经病理性疼痛, P38MAPK信号通路, 动物实验

Zhang Zhifeng, Yan Wenlu, Xia Ziwei.

Mechanism of alleviating neuropathic pain in rats by inhibiting the expression of P38MAPK signaling pathway [J]. International Medicine and Health Guidance News, 2024, 30(10): 1664-1667.

张志峰颜文璐夏紫薇.

抑制P38MAPK信号通路表达减轻大鼠神经病理性疼痛的机制 [J]. 国际医药卫生导报, 2024, 30(10): 1664-1667.

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