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A Novel Mechanism of Specialized Proresolving Lipid Mediators Mitigating Radicular Pain: The Negative Interaction with NLRP3 Inflammasome.
Neurochemical Research ( IF 4.4 ) Pub Date : 2020-05-14 , DOI: 10.1007/s11064-020-03050-x
Yi-Hao Wang 1, 2 , Yan Li 3 , Jun-Nan Wang 1 , Qing-Xiang Zhao 1 , Shuang Wen 1 , Si-Cong Wang 1 , Tao Sun 1
Affiliation  

Inhibition of immune and inflammatory reaction induced by the expose of nucleus pulposus (NP) could effectively ameliorate neuropathic pain in the lumbar disc herniation. Maresin1 (MaR1), as a macrophage-derived mediator of inflammation resolution, displayed potent anti-inflammatory action. In the present study, we attempted to elucidate the impact of MaR1 on radicular pain and the interaction with NLRP3 inflammasome. We established a rat model of non-compressive lumbar disc herniation and different administration (MaR1 or Caspase-1 inhibitor) was given to them. The paw withdrawal latency (PWL) and paw withdrawal thresholds (PWTs) were observed to assess pain behaviors. The spinal cord horns were collected and the levels of IL-1β and IL-18 were measured by ELISA. The mRNA and protein expression levels of NLRP3 inflammasome components were tested by RT-PCR, western blot and immunohistochemistry. The endogenous MaR1 levels of the spinal cord were analyzed using LC-MS/MS. The application of NP in the models lead to mechanical and thermal hypersensitivity, increased IL-1β and IL-18 levels and expressions of NLRP3 inflammasome components, which were reversed markedly by administration of MaR1. Caspase-1 inhibition also improved mechanical hypersensitivity, decreased the expressions of inflammatory cytokines and restrained the activation of inflammasome. Meanwhile, Caspase-1 inhibitor promoted the endogenous MaR1 synthesis, which was hindered in the pain models. Altogether, our study indicated that the negative interaction between MaR1 and NLRP3 inflammasome mediated the inflammatory response in spinal dorsal horn, which involved in the pathogenesis of radicular pain.

中文翻译:

一种特殊的促分解脂质介质减轻神经根疼痛的新机制:与 NLRP3 炎性体的负相互作用。

抑制髓核暴露引起的免疫和炎症反应可有效改善腰椎间盘突出症的神经性疼痛。Maresin1 (MaR1) 作为巨噬细胞衍生的炎症消退介质,显示出有效的抗炎作用。在本研究中,我们试图阐明 MaR1 对神经根性疼痛的影响以及与 NLRP3 炎性体的相互作用。我们建立了非压迫性腰椎间盘突出症大鼠模型,并对其进行了不同的给药(MaR1或Caspase-1抑制剂)。观察缩爪潜伏期 (PWL) 和缩爪阈值 (PWT) 以评估疼痛行为。收集脊髓角,用ELISA法测定IL-1β和IL-18的水平。通过RT-PCR、蛋白质印迹和免疫组织化学检测NLRP3炎性体成分的mRNA和蛋白表达水平。使用 LC-MS/MS 分析脊髓的内源性 MaR1 水平。NP 在模型中的应用导致机械和热超敏反应、增加的 IL-1β 和 IL-18 水平以及 NLRP3 炎性体成分的表达,这些通过施用 MaR1 显着逆转。Caspase-1 抑制也改善了机械超敏反应,降低了炎性细胞因子的表达并抑制了炎性体的活化。同时,Caspase-1 抑制剂促进内源性 MaR1 合成,这在疼痛模型中受到阻碍。共,
更新日期:2020-05-14
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