Wu Yuanyuan, Jiang Yongliang, Shao Xiaomei, He Xiaofen, Shen Zui, Shi Yan, Wang Chao, Fang Jianqiao
Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
Department of Acupuncture and Moxibustion, The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
J Pain Res. 2019 Nov 13;12:3067-3078. doi: 10.2147/JPR.S211826. eCollection 2019.
Clinical patients suffering from pain usually exhibit aversion to pain-associated environments (pain aversion). Electro-acupuncture (EA) has been proven to be effective for the treatment of pain aversion in our previous studies. The amygdala could have substantial consequences on emotion and pain consolidation as well as general pain aversion behavior, however, the underlying mechanism remains unclear.
The current study was performed to investigate Isobaric tags for relative and absolute quantitation (iTRAQ) based quantitative proteomic analysis of the amygdala in rats with complete Freund's adjuvant (CFA)-induced pain aversion, and comprehensive analysis of protein expression were performed to explore the underlying mechanism by which EA affects pain aversion.
Inflammatory pain was induced with an intraplantar injection of 100 μL of CFA in the plantar surface of the left hind paw of the male Spragure-Dawley (SD) rats. Then the CFA-induced conditioned place aversion (C-CPA) test was performed. EA stimulation on the bilateral Zusanli and Sanyinjiao acu-points was used for 14 days and the EA stimulation frequency is 2 Hz. Based on iTRAQ-based proteomics analysis, we investigated the protein expression in the amygdala.
EA can increase the paw withdrawal threshold in inflammatory pain induced by noxious stimulation. A total of 6319 proteins were quantified in amygdala. Of these identified proteins, 123 were identified in the pain aversion group relative to those in the saline group, and 125 significantly altered proteins were identified in the pain aversion + EA group relative to the pain aversion group. A total of 11 proteins were found to be differentially expressed in the amygdala of pain aversion and EA-treated rats. The expression of three proteins, glyceraldehyde-3-phosphate dehydrogenase, glutamate transporter-1, and p21-activated kinase 6, were confirmed to be consistent with the results of the proteome.
Our investigation demonstrated the possible mechanism of central nerve system by which EA intervetion on pain aversion.
临床疼痛患者通常表现出对疼痛相关环境的厌恶(疼痛厌恶)。在我们之前的研究中,电针(EA)已被证明对治疗疼痛厌恶有效。杏仁核可能对情绪、疼痛巩固以及一般疼痛厌恶行为有重大影响,然而,其潜在机制仍不清楚。
本研究旨在对完全弗氏佐剂(CFA)诱导的疼痛厌恶大鼠杏仁核进行基于相对和绝对定量等压标记(iTRAQ)的定量蛋白质组学分析,并对蛋白质表达进行综合分析,以探讨电针影响疼痛厌恶的潜在机制。
在雄性Spragure-Dawley(SD)大鼠左后爪足底注射100 μL CFA诱导炎性疼痛。然后进行CFA诱导的条件性位置厌恶(C-CPA)试验。对双侧足三里和三阴交穴位进行14天的电针刺激,电针刺激频率为2 Hz。基于iTRAQ的蛋白质组学分析,我们研究了杏仁核中的蛋白质表达。
电针可提高有害刺激诱导的炎性疼痛中的爪退缩阈值。杏仁核中共定量了6319种蛋白质。在这些鉴定出的蛋白质中,与生理盐水组相比,疼痛厌恶组中鉴定出123种,与疼痛厌恶组相比,疼痛厌恶+电针组中鉴定出125种显著改变的蛋白质。总共发现11种蛋白质在疼痛厌恶和电针治疗大鼠的杏仁核中差异表达。三种蛋白质,即甘油醛-3-磷酸脱氢酶、谷氨酸转运体-1和p21激活激酶6的表达被证实与蛋白质组结果一致。
我们的研究证明了电针干预疼痛厌恶的中枢神经系统可能机制。