Wang Yue, Ji Xiuru, Sun Yu, Wang Han, Wang Ting, Luo Tao, Cheng Yanyong, Yan Jia, Ni Dalong, Jiang Hong
Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P. R. China.
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China.
Adv Sci (Weinh). 2025 Aug;12(29):e02920. doi: 10.1002/advs.202502920. Epub 2025 May 21.
Neuropathic pain is a multifaceted syndrome posing significant challenges to patient quality of life and healthcare systems. Conventional treatments primarily focus on general pain modulation, which fail to address specific underlying mechanisms, leading to limited efficacy and infinite side effects. Calcitonin gene-related peptide (CGRP) has played a pivotal role in neuro-immune repair, contributing to vasodilation, nociception, and immune modulation following tissue injury. Herein, a bupivacaine-loaded cerium-based metal-organic framework (CUB) is designed to integrate sustained release of analgesia with immunomodulatory and antioxidant capabilities. In vivo models of chronic constriction injury (CCI) have demonstrated that CUB significantly reduced neuroinflammation, promoted M2 microglial polarization, and enhanced myelin regeneration for the prolonged analgesia. Deep mechanism analysis revealed that the designed CUB can significantly elevate TSP-1 expression to activate CGRP signal in modulating the neuro-immune interaction, contributing to the repair process. Notably, the CUB outperformed standalone bupivacaine or cerium nanoparticles in terms of pain relief, motor function recovery, and neuroglial regulation. The findings highlight the potential of CUB as a multifactorial therapeutic for treating neuropathic pain, offering new perspectives on the integration of nanotechnology in chronic pain management through neuro-immune pathways.
神经性疼痛是一种多方面的综合征，给患者的生活质量和医疗系统带来了重大挑战。传统治疗主要侧重于一般的疼痛调节，无法解决特定的潜在机制，导致疗效有限且副作用众多。降钙素基因相关肽（CGRP）在神经免疫修复中发挥了关键作用，在组织损伤后促进血管舒张、伤害感受和免疫调节。在此，设计了一种负载布比卡因的铈基金属有机框架（CUB），以将镇痛的持续释放与免疫调节和抗氧化能力相结合。慢性压迫损伤（CCI）的体内模型表明，CUB显著减轻神经炎症，促进M2小胶质细胞极化，并增强髓鞘再生以实现长期镇痛。深入的机制分析表明，设计的CUB可以显著提高TSP-1表达，以激活CGRP信号来调节神经免疫相互作用，促进修复过程。值得注意的是，在疼痛缓解、运动功能恢复和神经胶质调节方面，CUB优于单独的布比卡因或铈纳米颗粒。这些发现突出了CUB作为治疗神经性疼痛的多因素疗法的潜力，为通过神经免疫途径将纳米技术整合到慢性疼痛管理中提供了新的视角。
