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Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice

Neuropathic pain is one of the most important clinical consequences of injury to the somatosensory system. Nevertheless, the critical pathophysiological mechanisms involved in neuropathic pain development are poorly understood. In this study, we found that neuropathic pain is abrogated when the kynu...

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Autores principales: Maganin, Alexandre G., Souza, Guilherme R., Fonseca, Miriam D., Lopes, Alexandre H., Guimarães, Rafaela M., Dagostin, André, Cecilio, Nerry T., Mendes, Atlante S., Gonçalves, William A., Silva, Conceição E.A., Fernandes Gomes, Francisco Isaac, Mauriz Marques, Lucas M., Silva, Rangel L., Arruda, Letícia M., Santana, Denis A., Lemos, Henrique, Huang, Lei, Davoli-Ferreira, Marcela, Santana-Coelho, Danielle, Sant’Anna, Morena B., Kusuda, Ricardo, Talbot, Jhimmy, Pacholczyk, Gabriela, Buqui, Gabriela A., Lopes, Norberto P., Alves-Filho, Jose C., Leão, Ricardo M., O’Connor, Jason C., Cunha, Fernando Q., Mellor, Andrew, Cunha, Thiago M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9711882/
https://www.ncbi.nlm.nih.gov/pubmed/36227694
http://dx.doi.org/10.1172/JCI153805
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author Maganin, Alexandre G.
Souza, Guilherme R.
Fonseca, Miriam D.
Lopes, Alexandre H.
Guimarães, Rafaela M.
Dagostin, André
Cecilio, Nerry T.
Mendes, Atlante S.
Gonçalves, William A.
Silva, Conceição E.A.
Fernandes Gomes, Francisco Isaac
Mauriz Marques, Lucas M.
Silva, Rangel L.
Arruda, Letícia M.
Santana, Denis A.
Lemos, Henrique
Huang, Lei
Davoli-Ferreira, Marcela
Santana-Coelho, Danielle
Sant’Anna, Morena B.
Kusuda, Ricardo
Talbot, Jhimmy
Pacholczyk, Gabriela
Buqui, Gabriela A.
Lopes, Norberto P.
Alves-Filho, Jose C.
Leão, Ricardo M.
O’Connor, Jason C.
Cunha, Fernando Q.
Mellor, Andrew
Cunha, Thiago M.
author_facet Maganin, Alexandre G.
Souza, Guilherme R.
Fonseca, Miriam D.
Lopes, Alexandre H.
Guimarães, Rafaela M.
Dagostin, André
Cecilio, Nerry T.
Mendes, Atlante S.
Gonçalves, William A.
Silva, Conceição E.A.
Fernandes Gomes, Francisco Isaac
Mauriz Marques, Lucas M.
Silva, Rangel L.
Arruda, Letícia M.
Santana, Denis A.
Lemos, Henrique
Huang, Lei
Davoli-Ferreira, Marcela
Santana-Coelho, Danielle
Sant’Anna, Morena B.
Kusuda, Ricardo
Talbot, Jhimmy
Pacholczyk, Gabriela
Buqui, Gabriela A.
Lopes, Norberto P.
Alves-Filho, Jose C.
Leão, Ricardo M.
O’Connor, Jason C.
Cunha, Fernando Q.
Mellor, Andrew
Cunha, Thiago M.
author_sort Maganin, Alexandre G.
collection PubMed
description Neuropathic pain is one of the most important clinical consequences of injury to the somatosensory system. Nevertheless, the critical pathophysiological mechanisms involved in neuropathic pain development are poorly understood. In this study, we found that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is ablated pharmacologically or genetically. Mechanistically, it was found that IDO1-expressing dendritic cells (DCs) accumulated in the dorsal root leptomeninges and led to an increase in kynurenine levels in the spinal cord. In the spinal cord, kynurenine was metabolized by kynurenine-3-monooxygenase–expressing astrocytes into the pronociceptive metabolite 3-hydroxykynurenine. Ultimately, 3-hydroxyanthranilate 3,4-dioxygenase–derived quinolinic acid formed in the final step of the canonical KYNPATH was also involved in neuropathic pain development through the activation of the glutamatergic N-methyl-D-aspartate receptor. In conclusion, these data revealed a role for DCs driving neuropathic pain development through elevation of the KYNPATH. This paradigm offers potential new targets for drug development against this type of chronic pain.
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spelling pubmed-97118822022-12-05 Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice Maganin, Alexandre G. Souza, Guilherme R. Fonseca, Miriam D. Lopes, Alexandre H. Guimarães, Rafaela M. Dagostin, André Cecilio, Nerry T. Mendes, Atlante S. Gonçalves, William A. Silva, Conceição E.A. Fernandes Gomes, Francisco Isaac Mauriz Marques, Lucas M. Silva, Rangel L. Arruda, Letícia M. Santana, Denis A. Lemos, Henrique Huang, Lei Davoli-Ferreira, Marcela Santana-Coelho, Danielle Sant’Anna, Morena B. Kusuda, Ricardo Talbot, Jhimmy Pacholczyk, Gabriela Buqui, Gabriela A. Lopes, Norberto P. Alves-Filho, Jose C. Leão, Ricardo M. O’Connor, Jason C. Cunha, Fernando Q. Mellor, Andrew Cunha, Thiago M. J Clin Invest Research Article Neuropathic pain is one of the most important clinical consequences of injury to the somatosensory system. Nevertheless, the critical pathophysiological mechanisms involved in neuropathic pain development are poorly understood. In this study, we found that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is ablated pharmacologically or genetically. Mechanistically, it was found that IDO1-expressing dendritic cells (DCs) accumulated in the dorsal root leptomeninges and led to an increase in kynurenine levels in the spinal cord. In the spinal cord, kynurenine was metabolized by kynurenine-3-monooxygenase–expressing astrocytes into the pronociceptive metabolite 3-hydroxykynurenine. Ultimately, 3-hydroxyanthranilate 3,4-dioxygenase–derived quinolinic acid formed in the final step of the canonical KYNPATH was also involved in neuropathic pain development through the activation of the glutamatergic N-methyl-D-aspartate receptor. In conclusion, these data revealed a role for DCs driving neuropathic pain development through elevation of the KYNPATH. This paradigm offers potential new targets for drug development against this type of chronic pain. American Society for Clinical Investigation 2022-12-01 /pmc/articles/PMC9711882/ /pubmed/36227694 http://dx.doi.org/10.1172/JCI153805 Text en © 2022 Maganin et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Maganin, Alexandre G.
Souza, Guilherme R.
Fonseca, Miriam D.
Lopes, Alexandre H.
Guimarães, Rafaela M.
Dagostin, André
Cecilio, Nerry T.
Mendes, Atlante S.
Gonçalves, William A.
Silva, Conceição E.A.
Fernandes Gomes, Francisco Isaac
Mauriz Marques, Lucas M.
Silva, Rangel L.
Arruda, Letícia M.
Santana, Denis A.
Lemos, Henrique
Huang, Lei
Davoli-Ferreira, Marcela
Santana-Coelho, Danielle
Sant’Anna, Morena B.
Kusuda, Ricardo
Talbot, Jhimmy
Pacholczyk, Gabriela
Buqui, Gabriela A.
Lopes, Norberto P.
Alves-Filho, Jose C.
Leão, Ricardo M.
O’Connor, Jason C.
Cunha, Fernando Q.
Mellor, Andrew
Cunha, Thiago M.
Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice
title Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice
title_full Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice
title_fullStr Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice
title_full_unstemmed Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice
title_short Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice
title_sort meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9711882/
https://www.ncbi.nlm.nih.gov/pubmed/36227694
http://dx.doi.org/10.1172/JCI153805
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