Department of Pain Management, Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, Shandong, People's Republic of China.
Department of Pain Management, Ganzhou People's Hospital, Ganzhou, Jiangxi, China.
Neurochem Res. 2018 Dec;43(12):2384-2392. doi: 10.1007/s11064-018-2666-9. Epub 2018 Nov 15.
Neuroinflammation induced by protruded nucleus pulposus (NP) has been shown to play a significant role in facilitation of radicular pain. Resolvin D2 (RvD2), a novel member of resolvin family, exhibits potent anti-inflammatory, pro-resolving and antinociceptive effects. But the effect of RvD2 in radicular pain remains unknown. The radicular pain rat models were induced by application of NP to L5 dorsal root ganglion. Each animal received intrathecal injections of vehicle or RvD2 (10 ng µl or 100 ng µl). Mechanical thresholds were determined by measuring the paw withdrawal threshold for 7 days. The expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) in ipsilateral lumbar segment of rat spinal dorsal horns were measured by using ELISA and real time-PCR. Western blot was used to measure the expressions of phosphorylated Akt (p-Akt) and phosphorylated glycogen synthase kinase 3 beta (p-GSK-3β). The expressions and distributions of RvD2 receptor, G-protein-coupled receptor 18 (GPR18), were also explored in the spinal cord of rats by using double-label immunofluorescence. RvD2 treatment caused significant reductions in the intensity of mechanical hypersensitivity and spinal expressions of TNF-α and IL-6. Meanwhile, RvD2 increased the expressions of TGF-β1 and regulated Akt/GSK-3β signaling. Furthermore, immunofluorescence showed that GPR18 colocalized with neurons and astrocytes in spinal cord. The results suggested that RvD2 might attenuate mechanical allodynia via regulating the expressions of inflammatory mediators and activation of Akt/GSK-3β signal pathway. RvD2 might offer a hopeful method for radicular pain therapy.
突出的椎间盘（NP）引起的神经炎症已被证明在促进神经根痛中起重要作用。解析素 D2（RvD2），解析素家族的一个新成员，具有强大的抗炎、促解决和抗伤害作用。但 RvD2 在神经根痛中的作用尚不清楚。NP 应用于 L5 背根神经节诱导神经根痛大鼠模型。每只动物接受鞘内注射载体或 RvD2（10ngµl 或 100ngµl）。通过测量 7 天的足底退缩阈值来确定机械阈值。采用 ELISA 和实时 PCR 测定大鼠脊髓背角同侧腰椎段肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和转化生长因子-β1（TGF-β1）的表达。Western blot 用于测量磷酸化 Akt（p-Akt）和磷酸化糖原合成酶激酶 3β（p-GSK-3β）的表达。通过双重免疫荧光法还探索了 RvD2 受体、G 蛋白偶联受体 18（GPR18）在大鼠脊髓中的表达和分布。RvD2 处理导致机械性超敏反应强度和脊髓 TNF-α和 IL-6表达显著降低。同时，RvD2 增加了 TGF-β1 的表达并调节了 Akt/GSK-3β信号通路。此外，免疫荧光显示 GPR18 与脊髓中的神经元和星形胶质细胞共定位。结果表明，RvD2 可能通过调节炎症介质的表达和激活 Akt/GSK-3β信号通路来减轻机械性痛觉过敏。RvD2 可能为神经根痛治疗提供一种有希望的方法。
