Bo Cunju, Liu Xiaoming, Liu Yongjian, Xu Lingjun, Huang Qiaodong
Department of Pain Medicine, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, Guangdong, China.
Eur J Med Res. 2025 Mar 20;30(1):189. doi: 10.1186/s40001-025-02424-7.
Neuropathic pain is characterized by hyperalgesia, allodynia, and inflammation and it is often resistant to treatment. The formyl peptide receptor 2 (ALX/FPR2), a G-protein-coupled receptor, has been implicated in resolving inflammation, making its agonist, Resolvin D1 (RvD1), a potential therapeutic agent. Previous studies suggest that RvD1 alleviates neuropathic pain via anti-inflammatory effects, but its mechanisms remain unclear, particularly in relation to microglial activation and the brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway.
To investigate the analgesic effects of RvD1 in a spared nerve injury (SNI) model of neuropathic pain and explore its mechanisms through the regulation of neuroinflammation and the BDNF/TrkB signaling pathway.
SNI mice received intrathecal RvD1 at varying doses (10-40 ng) to determine its efficacy in reducing mechanical allodynia and thermal sensitivity. The anti-inflammatory effects of RvD1 were assessed using ELISA, immunofluorescence, and western blotting to measure the expression of pro-inflammatory cytokines and BDNF. The involvement of ALX/FPR2 and TrkB receptors was further examined using antagonists Boc2 and K252a.
RvD1 significantly reduced mechanical and thermal allodynia in SNI mice in a dose-dependent manner. RvD1 also decreased microglial activation and expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and BDNF in both in vivo and in vitro models. These effects were reversed by Boc2 and K252a, confirming that the analgesic actions of RvD1 are mediated via the ALX/FPR2 receptor and inhibition of BDNF/TrkB signaling.
RvD1 alleviates neuropathic pain by reducing neuroinflammation through the ALX/FPR2 receptor and suppressing BDNF/TrkB signaling. These findings suggest RvD1 as a promising therapeutic agent for neuropathic pain management.
神经性疼痛的特征为痛觉过敏、异常性疼痛和炎症，且通常对治疗具有抗性。甲酰肽受体2（ALX/FPR2）是一种G蛋白偶联受体，与炎症消退有关，其激动剂消退素D1（RvD1）是一种潜在的治疗药物。先前的研究表明，RvD1通过抗炎作用减轻神经性疼痛，但其机制仍不清楚，尤其是与小胶质细胞激活以及脑源性神经营养因子（BDNF）/酪氨酸激酶受体B（TrkB）信号通路相关的机制。
研究RvD1在神经性疼痛的 spared nerve injury（SNI）模型中的镇痛作用，并通过调节神经炎症和BDNF/TrkB信号通路探索其机制。
SNI小鼠接受不同剂量（10 - 40 ng）的鞘内注射RvD1，以确定其在降低机械性异常性疼痛和热敏感性方面的疗效。使用酶联免疫吸附测定（ELISA）、免疫荧光和蛋白质免疫印迹法评估RvD1的抗炎作用，以测量促炎细胞因子和BDNF的表达。使用拮抗剂Boc2和K252a进一步研究ALX/FPR2和TrkB受体的参与情况。
RvD1以剂量依赖性方式显著降低了SNI小鼠的机械性和热异常性疼痛。在体内和体外模型中，RvD1还降低了小胶质细胞激活以及促炎细胞因子（肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6）和BDNF的表达。Boc2和K252a逆转了这些作用，证实RvD1的镇痛作用是通过ALX/FPR2受体介导并抑制BDNF/TrkB信号传导。
RvD1通过ALX/FPR2受体减轻神经炎症并抑制BDNF/TrkB信号传导来缓解神经性疼痛。这些发现表明RvD1是一种用于管理神经性疼痛的有前景的治疗药物。
