Xia Shuangyin, Qin Xiunan, Wang Yaping
Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Pain Management, The Second Xiangya Hospital, Central South University, Changsha, China.
Front Pharmacol. 2025 Aug 6;16:1590624. doi: 10.3389/fphar.2025.1590624. eCollection 2025.
Trigeminal neuralgia (TN), a debilitating neuropathic pain disorder, is characterized by demyelination and neuroinflammation, with limited therapies addressing its underlying pathophysiology. Bone Morphogenetic Protein 4 (BMP4) signaling and chemokine CCL5 are implicated in neuroinflammation and oligodendrocyte dysfunction, presenting potential therapeutic targets.
Peptide nanomicelles loaded with the BMP4 inhibitor DMH1 (NM@DMH1) were synthesized and characterized for stability, drug release kinetics, and biocompatibility. studies assessed oligodendrocyte progenitor cell (OPC) differentiation and anti-inflammatory effects in lipopolysaccharide-induced models. A rat TN model (chronic infraorbital nerve compression) evaluated NM@DMH1's efficacy in alleviating mechanical allodynia, demyelination, and neuroinflammation. Mechanistic roles of CCL5 were explored using recombinant protein supplementation.
NM@DMH1 exhibited uniform nanostructure (120 nm), high encapsulation efficiency (82%), and pH-responsive sustained release. Treatment enhanced OPC differentiation, reduced pro-inflammatory cytokines (IL-6, TNF-α, IL-1β), and suppressed CCL5 expression . In TN rats, NM@DMH1 significantly attenuated mechanical pain hypersensitivity (p < 0.01 vs model), restored myelin markers (MBP, MOG), and inhibited neuroinflammatory infiltration. CCL5 supplementation reversed therapeutic benefits, confirming its pivotal role.
NM@DMH1 represents a nanotechnology-driven strategy targeting TN pathogenesis by promoting remyelination and suppressing CCL5-mediated neuroinflammation. This study advances precision drug delivery for neuropathic pain and highlights CCL5 as a novel therapeutic node, offering translational potential for TN and related neuroinflammatory disorders.
三叉神经痛（TN）是一种使人衰弱的神经性疼痛疾病，其特征为脱髓鞘和神经炎症，针对其潜在病理生理学的治疗方法有限。骨形态发生蛋白4（BMP4）信号传导和趋化因子CCL5与神经炎症和少突胶质细胞功能障碍有关，是潜在的治疗靶点。
合成了负载BMP4抑制剂DMH1的肽纳米胶束（NM@DMH1），并对其稳定性、药物释放动力学和生物相容性进行了表征。研究评估了其在脂多糖诱导模型中对少突胶质前体细胞（OPC）分化和抗炎作用。大鼠TN模型（慢性眶下神经压迫）评估了NM@DMH1在减轻机械性异常性疼痛、脱髓鞘和神经炎症方面的疗效。使用重组蛋白补充剂探索CCL5的作用机制。
NM@DMH1呈现均匀的纳米结构（120纳米）、高包封率（82%）和pH响应性缓释。治疗可增强OPC分化，降低促炎细胞因子（IL-6、TNF-α、IL-1β），并抑制CCL5表达。在TN大鼠中，NM@DMH1显著减轻机械性疼痛超敏反应（与模型组相比，p<0.01），恢复髓鞘标志物（MBP、MOG），并抑制神经炎性浸润。补充CCL5可逆转治疗效果，证实了其关键作用。
NM@DMH1代表了一种纳米技术驱动的策略，通过促进髓鞘再生和抑制CCL5介导的神经炎症来靶向TN发病机制。本研究推进了神经性疼痛的精准药物递送，并突出了CCL5作为一个新的治疗节点，为TN和相关神经炎症性疾病提供了转化潜力。
