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Intracellular mGluR5 plays a critical role in neuropathic pain
Spinal mGluR5 is a key mediator of neuroplasticity underlying persistent pain. Although brain mGluR5 is localized on cell surface and intracellular membranes, neither the presence nor physiological role of spinal intracellular mGluR5 is established. Here we show that in spinal dorsal horn neurons &g...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742982/ https://www.ncbi.nlm.nih.gov/pubmed/26837579 http://dx.doi.org/10.1038/ncomms10604 |
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author | Vincent, Kathleen Cornea, Virginia M. Jong, Yuh-Jiin I. Laferrière, André Kumar, Naresh Mickeviciute, Aiste Fung, Jollee S. T. Bandegi, Pouya Ribeiro-da-Silva, Alfredo O'Malley, Karen L. Coderre, Terence J. |
author_facet | Vincent, Kathleen Cornea, Virginia M. Jong, Yuh-Jiin I. Laferrière, André Kumar, Naresh Mickeviciute, Aiste Fung, Jollee S. T. Bandegi, Pouya Ribeiro-da-Silva, Alfredo O'Malley, Karen L. Coderre, Terence J. |
author_sort | Vincent, Kathleen |
collection | PubMed |
description | Spinal mGluR5 is a key mediator of neuroplasticity underlying persistent pain. Although brain mGluR5 is localized on cell surface and intracellular membranes, neither the presence nor physiological role of spinal intracellular mGluR5 is established. Here we show that in spinal dorsal horn neurons >80% of mGluR5 is intracellular, of which ∼60% is located on nuclear membranes, where activation leads to sustained Ca(2+) responses. Nerve injury inducing nociceptive hypersensitivity also increases the expression of nuclear mGluR5 and receptor-mediated phosphorylated-ERK1/2, Arc/Arg3.1 and c-fos. Spinal blockade of intracellular mGluR5 reduces neuropathic pain behaviours and signalling molecules, whereas blockade of cell-surface mGluR5 has little effect. Decreasing intracellular glutamate via blocking EAAT-3, mimics the effects of intracellular mGluR5 antagonism. These findings show a direct link between an intracellular GPCR and behavioural expression in vivo. Blockade of intracellular mGluR5 represents a new strategy for the development of effective therapies for persistent pain. |
format | Online Article Text |
id | pubmed-4742982 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47429822016-03-04 Intracellular mGluR5 plays a critical role in neuropathic pain Vincent, Kathleen Cornea, Virginia M. Jong, Yuh-Jiin I. Laferrière, André Kumar, Naresh Mickeviciute, Aiste Fung, Jollee S. T. Bandegi, Pouya Ribeiro-da-Silva, Alfredo O'Malley, Karen L. Coderre, Terence J. Nat Commun Article Spinal mGluR5 is a key mediator of neuroplasticity underlying persistent pain. Although brain mGluR5 is localized on cell surface and intracellular membranes, neither the presence nor physiological role of spinal intracellular mGluR5 is established. Here we show that in spinal dorsal horn neurons >80% of mGluR5 is intracellular, of which ∼60% is located on nuclear membranes, where activation leads to sustained Ca(2+) responses. Nerve injury inducing nociceptive hypersensitivity also increases the expression of nuclear mGluR5 and receptor-mediated phosphorylated-ERK1/2, Arc/Arg3.1 and c-fos. Spinal blockade of intracellular mGluR5 reduces neuropathic pain behaviours and signalling molecules, whereas blockade of cell-surface mGluR5 has little effect. Decreasing intracellular glutamate via blocking EAAT-3, mimics the effects of intracellular mGluR5 antagonism. These findings show a direct link between an intracellular GPCR and behavioural expression in vivo. Blockade of intracellular mGluR5 represents a new strategy for the development of effective therapies for persistent pain. Nature Publishing Group 2016-02-03 /pmc/articles/PMC4742982/ /pubmed/26837579 http://dx.doi.org/10.1038/ncomms10604 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Vincent, Kathleen Cornea, Virginia M. Jong, Yuh-Jiin I. Laferrière, André Kumar, Naresh Mickeviciute, Aiste Fung, Jollee S. T. Bandegi, Pouya Ribeiro-da-Silva, Alfredo O'Malley, Karen L. Coderre, Terence J. Intracellular mGluR5 plays a critical role in neuropathic pain |
title | Intracellular mGluR5 plays a critical role in neuropathic pain |
title_full | Intracellular mGluR5 plays a critical role in neuropathic pain |
title_fullStr | Intracellular mGluR5 plays a critical role in neuropathic pain |
title_full_unstemmed | Intracellular mGluR5 plays a critical role in neuropathic pain |
title_short | Intracellular mGluR5 plays a critical role in neuropathic pain |
title_sort | intracellular mglur5 plays a critical role in neuropathic pain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742982/ https://www.ncbi.nlm.nih.gov/pubmed/26837579 http://dx.doi.org/10.1038/ncomms10604 |
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