ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1590624
DMH1-Loaded Peptide Nanomicelles Restore Myelin and Attenuate Neuroinflammation in Trigeminal Neuralgia via CCL5 Suppression
Provisionally accepted
- Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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Background: 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.Methods: Peptide nanomicelles loaded with the BMP4 inhibitor DMH1 (NM@DMH1) were synthesized and characterized for stability, drug release kinetics, and biocompatibility. In vitro 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.Results: 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 vitro. 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.Conclusion: 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.
Keywords: Peptide Nanobundles, Bone Morphogenetic Protein 4, C-C motif chemokine ligand 5, oligodendrocyte progenitor cells, Demyelinating lesions, Trigeminal Neuralgia, Inflammation suppression
Received: 10 Mar 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Xia, Qin and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yaping Wang, Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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