Schwann cell autophagy counteracts the onset and chronification of neuropathic pain
| العنوان: | Schwann cell autophagy counteracts the onset and chronification of neuropathic pain |
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| المؤلفون: | Walter Malorni, Valentina Vacca, Francesco Cecconi, Sara Marinelli, Antonella Tinari, Luisa Pieroni, Flaminia Pavone, Francesca Nazio, Marcello D'Amelio, Andrea Urbani, Laura Ciarlo |
| المصدر: | Pain (Amst. Online) 155 (2014): 93–107. doi:10.1016/j.pain.2013.09.013 info:cnr-pdr/source/autori:Marinelli S.1; Nazio F.1; Tinari A.3; Ciarlo L.4; D'Amelio M.5; Pieroni L.6; Vacca V.1; Urbani A.6; Cecconi F.7; Malorni W.8; Pavone F.9/titolo:Schwann cell autophagy counteracts the onset and chronification of neuropathic pain/doi:10.1016%2Fj.pain.2013.09.013/rivista:Pain (Amst. Online)/anno:2014/pagina_da:93/pagina_a:107/intervallo_pagine:93–107/volume:155 |
| بيانات النشر: | Elsevier Health Sciences, Amsterdam , Paesi Bassi, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Wallerian degeneration, Time Factors, Chronic pain, Transgenic, Myelin, Sciatica, Mice, Autophagic flux, Pain Measurement, CD11b Antigen, Settore BIO/12, Adaptor Proteins, Sciatic Nerve, Cell biology, medicine.anatomical_structure, Neurology, Neuropathic pain, Immunohistochemistry, Microtubule-Associated Proteins, Immunosuppressive Agents, Genetically modified mouse, Settore BIO/06, Green Fluorescent Proteins, Schwann cell, Mice, Transgenic, Biology, Glia, Glial Fibrillary Acidic Protein, medicine, Autophagy, Animals, Behaviour, Antigens, Adaptor Proteins, Signal Transducing, Sirolimus, Disease Models, Animal, Schwann Cells, Adenine, Gene Expression Regulation, Antigens, CD11b, Animal, Regeneration (biology), CD11b, fungi, Signal Transducing, medicine.disease, Anesthesiology and Pain Medicine, Disease Models, Neurology (clinical), Neuroscience |
| الوصف: | 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. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91b41e23aca9ba31cf0463f17ade5ad5Test https://publications.cnr.it/doc/280633Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....91b41e23aca9ba31cf0463f17ade5ad5 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |