The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Schwann cell autophagy counteracts the onset and chronification of neuropathic pain
Abstract
Axonal degeneration in peripheral nerves after injury is accompanied by myelin degradation initiated by Schwann cells (SCs). These cells activate autophagy, a ubiquitous cytoprotective process essential for degradation and recycling of cellular constituents. Concomitantly to nerve insult and axonal degeneration, neuropathic pain (NeP) arises. The role of SC autophagy in the mechanisms underlying NeP is still unknown. In this study, we examined the role of the autophagy during the early phase of Wallerian degeneration in NeP induction and chronification by using a murine model of peripheral nerve lesion (chronic constriction injury). We demonstrate that the autophagy inducer rapamycin, administered in the first week after nerve damage, induces long-lasting analgesic and antiinflammatory effects, facilitates nerve regeneration, and prevents pain chronification. Conversely, when autophagy is altered, by means of autophagic inhibitor 3-methyladenine administration or as occurs in activating molecule in Beclin-1-regulated autophagy transgenic mice (Ambra1(+/gt)), NeP is dramatically enhanced and prolonged. Immunohistochemical and ultrastructural evaluations show that rapamycin is able to increase autophagic flux in SCs, to accelerate myelin compaction, and to reduce inflammatory and immune reaction. Proteomic analysis combined with bioinformatic analysis suggests that a redox-sensitive mechanism could be responsible for SC autophagy activation. These data suggest that a deficiency of autophagic activity in SCs can be an early event in the origin of NeP chronification and that autophagy modulation may represent a powerful pharmacological approach to prevent the onset and chronification of NeP in the clinical setting.
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“Conversely, stimulating Schwann cell autophagy with rapamycin promotes myelination and improves peripheral nerve regeneration [465,466].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [466]
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Metadata
- Authors
- Marinelli, S., Nazio, F., Tinari, A., Ciarlo, L., D'Amelio, M., Pieroni, L., Vacca, V., Urbani, A., Cecconi, F., Malorni, W., & Pavone, F.
- Affiliations
- University of Rome Tor Vergata (IT)
- Fondazione Santa Lucia (IT)
- Istituto Superiore di Sanità (IT)
- Corresponding author
- Pavone, Flaminia
- ORCID
- Venue
- Pain
- Published
- 2014-01
- Volume
- 155
- Issue
- 1
- Pages
- 93-107
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2078852360
- Cited by
- 119
- References
- 68
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 11 · 2023: 16 · 2022: 15 · 2021: 11 · 2020: 9 · 2019: 9 · 2018: 8 · 2017: 3 · 2016: 12 · 2015: 9 · 2014: 2
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- Schwann cells, autophagy, neuropathic pain, pain chronification, Wallerian degeneration, chronic constriction injury, rapamycin, myelin degradation, axonal degeneration, nerve regeneration, Beclin-1, 3-methyladenine, redox signaling, neuroinflammation, peripheral nerve injury
- MeSH terms
- Adenine, Animals, Autophagy, Disease Models, Animal, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Immunosuppressive Agents, Mice, Transgenic, Microtubule-Associated Proteins, Pain Measurement, Schwann Cells, Sciatic Nerve, Sciatica, Time Factors, Sirolimus, CD11b Antigen, Adaptor Proteins, Signal Transducing, Green Fluorescent Proteins, Mice
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