College of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan.
Department of Psychiatry, Taipei Medical University-Wan Fang Medical Center, Taipei, Taiwan.
Brain Behav Immun. 2020 Oct;89:604-614. doi: 10.1016/j.bbi.2020.06.033. Epub 2020 Jul 5.
Chronic pain and depression are conditions that are highly comorbid and present with overlapping clinical presentations and common pathological biological pathways in neuroinflammation, both of which can be reversed by the use of electroacupuncture (EA) and omega-3 polyunsaturated fatty acids (PUFAs). Transient receptor potential V1 (TRPV1), a Ca permeable ion channel that can be activated by inflammation, is reported to be involved in the development of chronic pain and depression. Here, we investigated the role of TRPV1 and its related pathways in the murine models of cold stress-induced nociception and depression. Female C57BL/6 wild type and TRPV1 knockout mice were subjected to intermittent cold-stress (ICS) to initiate depressive-like and chronic pain behaviors, respectively. The Bio-Plex ELISA technique was utilized to analyze inflammatory mediators in mice plasma. The western blot and immunostaining techniques were used to analyze the presence of TRPV1 and related molecules in the medial prefrontal cortex (mPFC), hippocampus, periaqueductal gray (PAG), and amygdala. The ICS model significantly induced chronic pain (mechanical: 2.55 ± 0.31 g; thermal: 8.12 ± 0.87 s) and depressive-like behaviors (10.95 ± 0.95% in the center zone; 53.14 ± 4.01% in immobility). The treatment efficacy of EA, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were observed in both nociceptive and depression test results. Inflammatory mediators were increased after ICS induction and further reversed by the use of EA, EPA and DHA. A majority of TRPV1 proteins and related molecules were significantly decreased in the mPFC, hippocampus and PAG of mice. This decrease can be reversed by the use of EA, EPA and DHA. In contrast, these molecules were increased in the mice's amygdala, and were attenuated by the use of EA, EPA and DHA. Our findings indicate that these inflammatory mediators can regulate the TRPV1 signaling pathway and initiate new potential therapeutic targets for chronic pain and depression treatment.
慢性疼痛和抑郁症是高度共病的疾病，表现出重叠的临床特征和神经炎症中的共同病理生物学途径，这两种疾病都可以通过电针（EA）和ω-3 多不饱和脂肪酸（PUFAs）逆转。瞬时受体电位 V1（TRPV1）是一种可以被炎症激活的 Ca 通透性离子通道，据报道与慢性疼痛和抑郁症的发展有关。在这里，我们研究了 TRPV1 及其相关途径在冷应激诱导的痛觉和抑郁的小鼠模型中的作用。雌性 C57BL/6 野生型和 TRPV1 敲除小鼠分别接受间歇性冷应激（ICS）以引发抑郁样和慢性疼痛行为。生物素标记的多重 ELISA 技术用于分析小鼠血浆中的炎症介质。Western blot 和免疫染色技术用于分析中前额叶皮层（mPFC）、海马体、导水管周围灰质（PAG）和杏仁核中 TRPV1 及其相关分子的存在。ICS 模型显著诱导慢性疼痛（机械：2.55±0.31g；热：8.12±0.87s）和抑郁样行为（中央区 10.95±0.95%；不动 53.14±4.01%）。EA、二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）的治疗效果在痛觉和抑郁测试结果中均观察到。ICS 诱导后炎症介质增加，EA、EPA 和 DHA 进一步逆转。大多数 TRPV1 蛋白及其相关分子在 mPFC、海马体和 PAG 中的表达显著降低。这种减少可以通过使用 EA、EPA 和 DHA 来逆转。相比之下，这些分子在小鼠的杏仁核中增加，并通过使用 EA、EPA 和 DHA 来减弱。我们的研究结果表明，这些炎症介质可以调节 TRPV1 信号通路，并为慢性疼痛和抑郁症的治疗提供新的潜在治疗靶点。
