Cited by 119Pain Mechanisms and TreatmentsAutophagy in Disease and TherapyNerve injury and regeneration

Schwann cell autophagy counteracts the onset and chronification of neuropathic pain

Marinelli, Sara, Nazio, Francesca, Tinari, Antonella, Ciarlo, Laura, D'Amelio, Marcello, Pieroni, Luisa, Vacca, Valentina, Urbani, Andrea +3 more·2014·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.

Integrity signals

Registry

Crossref · 10.1016/j.pain.2013.09.013

Cites

68 of 68 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Stimulating Schwann cell autophagy with rapamycin promotes myelination and improves peripheral nerve regeneration.

    “Conversely, stimulating Schwann cell autophagy with rapamycin promotes myelination and improves peripheral nerve regeneration [465,466].”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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
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 › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Epidemiology › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review