Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021, Shandong, China.
Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao, 266003, Shandong, China.
Neurochem Res. 2020 Aug;45(8):1860-1869. doi: 10.1007/s11064-020-03050-x. Epub 2020 May 14.
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.
抑制由髓核暴露引起的免疫和炎症反应可以有效改善腰椎间盘突出症的神经病理性疼痛。maresin1（MaR1）作为一种巨噬细胞来源的炎症消退介质，具有强大的抗炎作用。在本研究中，我们试图阐明 MaR1 对神经根痛的影响及其与 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）。观察爪退缩潜伏期（PWL）和爪退缩阈值（PWTs）来评估疼痛行为。收集脊髓角，通过 ELISA 测定 IL-1β和 IL-18 的水平。通过 RT-PCR、western blot 和免疫组化检测 NLRP3 炎性体成分的 mRNA 和蛋白表达水平。使用 LC-MS/MS 分析脊髓内源性 MaR1 水平。NP 在模型中的应用导致机械和热敏感性增加，IL-1β和 IL-18 水平升高，NLRP3 炎性体成分表达增强，MaR1 的给药明显逆转了这一现象。Caspase-1 抑制剂也改善了机械性过敏，降低了炎症细胞因子的表达，并抑制了炎性体的激活。同时，Caspase-1 抑制剂促进了内源性 MaR1 的合成，而这种合成在疼痛模型中受到阻碍。总之，我们的研究表明，MaR1 和 NLRP3 炎性体之间的负相互作用介导了脊髓背角的炎症反应，这与神经根痛的发病机制有关。
