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Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice
It is known that transient receptor potential ankyrin 1 (TRPA1) channels, expressed by nociceptors, contribute to neuropathic pain. Here we show that TRPA1 is also expressed in Schwann cells. We found that in mice with partial sciatic nerve ligation, TRPA1 silencing in nociceptors attenuated mechani...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709495/ https://www.ncbi.nlm.nih.gov/pubmed/29192190 http://dx.doi.org/10.1038/s41467-017-01739-2 |
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author | De Logu, Francesco Nassini, Romina Materazzi, Serena Carvalho Gonçalves, Muryel Nosi, Daniele Rossi Degl’Innocenti, Duccio Marone, Ilaria M. Ferreira, Juliano Li Puma, Simone Benemei, Silvia Trevisan, Gabriela Souza Monteiro de Araújo, Daniel Patacchini, Riccardo Bunnett, Nigel W. Geppetti, Pierangelo |
author_facet | De Logu, Francesco Nassini, Romina Materazzi, Serena Carvalho Gonçalves, Muryel Nosi, Daniele Rossi Degl’Innocenti, Duccio Marone, Ilaria M. Ferreira, Juliano Li Puma, Simone Benemei, Silvia Trevisan, Gabriela Souza Monteiro de Araújo, Daniel Patacchini, Riccardo Bunnett, Nigel W. Geppetti, Pierangelo |
author_sort | De Logu, Francesco |
collection | PubMed |
description | It is known that transient receptor potential ankyrin 1 (TRPA1) channels, expressed by nociceptors, contribute to neuropathic pain. Here we show that TRPA1 is also expressed in Schwann cells. We found that in mice with partial sciatic nerve ligation, TRPA1 silencing in nociceptors attenuated mechanical allodynia, without affecting macrophage infiltration and oxidative stress, whereas TRPA1 silencing in Schwann cells reduced both allodynia and neuroinflammation. Activation of Schwann cell TRPA1 evoked NADPH oxidase 1 (NOX1)-dependent H(2)O(2) release, and silencing or blocking Schwann cell NOX1 attenuated nerve injury-induced macrophage infiltration, oxidative stress and allodynia. Furthermore, the NOX2-dependent oxidative burst, produced by macrophages recruited to the perineural space activated the TRPA1–NOX1 pathway in Schwann cells, but not TRPA1 in nociceptors. Schwann cell TRPA1 generates a spatially constrained gradient of oxidative stress, which maintains macrophage infiltration to the injured nerve, and sends paracrine signals to activate TRPA1 of ensheathed nociceptors to sustain mechanical allodynia. |
format | Online Article Text |
id | pubmed-5709495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57094952017-12-04 Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice De Logu, Francesco Nassini, Romina Materazzi, Serena Carvalho Gonçalves, Muryel Nosi, Daniele Rossi Degl’Innocenti, Duccio Marone, Ilaria M. Ferreira, Juliano Li Puma, Simone Benemei, Silvia Trevisan, Gabriela Souza Monteiro de Araújo, Daniel Patacchini, Riccardo Bunnett, Nigel W. Geppetti, Pierangelo Nat Commun Article It is known that transient receptor potential ankyrin 1 (TRPA1) channels, expressed by nociceptors, contribute to neuropathic pain. Here we show that TRPA1 is also expressed in Schwann cells. We found that in mice with partial sciatic nerve ligation, TRPA1 silencing in nociceptors attenuated mechanical allodynia, without affecting macrophage infiltration and oxidative stress, whereas TRPA1 silencing in Schwann cells reduced both allodynia and neuroinflammation. Activation of Schwann cell TRPA1 evoked NADPH oxidase 1 (NOX1)-dependent H(2)O(2) release, and silencing or blocking Schwann cell NOX1 attenuated nerve injury-induced macrophage infiltration, oxidative stress and allodynia. Furthermore, the NOX2-dependent oxidative burst, produced by macrophages recruited to the perineural space activated the TRPA1–NOX1 pathway in Schwann cells, but not TRPA1 in nociceptors. Schwann cell TRPA1 generates a spatially constrained gradient of oxidative stress, which maintains macrophage infiltration to the injured nerve, and sends paracrine signals to activate TRPA1 of ensheathed nociceptors to sustain mechanical allodynia. Nature Publishing Group UK 2017-12-01 /pmc/articles/PMC5709495/ /pubmed/29192190 http://dx.doi.org/10.1038/s41467-017-01739-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article De Logu, Francesco Nassini, Romina Materazzi, Serena Carvalho Gonçalves, Muryel Nosi, Daniele Rossi Degl’Innocenti, Duccio Marone, Ilaria M. Ferreira, Juliano Li Puma, Simone Benemei, Silvia Trevisan, Gabriela Souza Monteiro de Araújo, Daniel Patacchini, Riccardo Bunnett, Nigel W. Geppetti, Pierangelo Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice |
title | Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice |
title_full | Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice |
title_fullStr | Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice |
title_full_unstemmed | Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice |
title_short | Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice |
title_sort | schwann cell trpa1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709495/ https://www.ncbi.nlm.nih.gov/pubmed/29192190 http://dx.doi.org/10.1038/s41467-017-01739-2 |
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