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Endothelin type A receptors mediate pain in a mouse model of sickle cell disease
Sickle cell disease is associated with acute painful episodes and chronic intractable pain. Endothelin-1, a known pain inducer, is elevated in the blood plasma of both sickle cell patients and mouse models of sickle cell disease. We show here that the levels of endothelin-1 and its endothelin type A...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ferrata Storti Foundation
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029538/ https://www.ncbi.nlm.nih.gov/pubmed/29545351 http://dx.doi.org/10.3324/haematol.2017.187013 |
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author | Lutz, Brianna Marie Wu, Shaogen Gu, Xiyao Atianjoh, Fidelis E. Li, Zhen Fox, Brandon M. Pollock, David M. Tao, Yuan-Xiang |
author_facet | Lutz, Brianna Marie Wu, Shaogen Gu, Xiyao Atianjoh, Fidelis E. Li, Zhen Fox, Brandon M. Pollock, David M. Tao, Yuan-Xiang |
author_sort | Lutz, Brianna Marie |
collection | PubMed |
description | Sickle cell disease is associated with acute painful episodes and chronic intractable pain. Endothelin-1, a known pain inducer, is elevated in the blood plasma of both sickle cell patients and mouse models of sickle cell disease. We show here that the levels of endothelin-1 and its endothelin type A receptor are increased in the dorsal root ganglia of a mouse model of sickle cell disease. Pharmacologic inhibition or neuron-specific knockdown of endothelin type A receptors in primary sensory neurons of dorsal root ganglia alleviated basal and post-hypoxia evoked pain hypersensitivities in sickle cell mice. Mechanistically, endothelin type A receptors contribute to sickle cell disease-associated pain likely through the activation of NF-κB-induced Nav1.8 channel upregulation in primary sensory neurons of sickle cell mice. Our findings suggest that endothelin type A receptor is a potential target for the management of sickle cell disease-associated pain, although this expectation needs to be further verified in clinical settings. |
format | Online Article Text |
id | pubmed-6029538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Ferrata Storti Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-60295382018-07-16 Endothelin type A receptors mediate pain in a mouse model of sickle cell disease Lutz, Brianna Marie Wu, Shaogen Gu, Xiyao Atianjoh, Fidelis E. Li, Zhen Fox, Brandon M. Pollock, David M. Tao, Yuan-Xiang Haematologica Article Sickle cell disease is associated with acute painful episodes and chronic intractable pain. Endothelin-1, a known pain inducer, is elevated in the blood plasma of both sickle cell patients and mouse models of sickle cell disease. We show here that the levels of endothelin-1 and its endothelin type A receptor are increased in the dorsal root ganglia of a mouse model of sickle cell disease. Pharmacologic inhibition or neuron-specific knockdown of endothelin type A receptors in primary sensory neurons of dorsal root ganglia alleviated basal and post-hypoxia evoked pain hypersensitivities in sickle cell mice. Mechanistically, endothelin type A receptors contribute to sickle cell disease-associated pain likely through the activation of NF-κB-induced Nav1.8 channel upregulation in primary sensory neurons of sickle cell mice. Our findings suggest that endothelin type A receptor is a potential target for the management of sickle cell disease-associated pain, although this expectation needs to be further verified in clinical settings. Ferrata Storti Foundation 2018-07 /pmc/articles/PMC6029538/ /pubmed/29545351 http://dx.doi.org/10.3324/haematol.2017.187013 Text en Copyright© 2018 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher. |
spellingShingle | Article Lutz, Brianna Marie Wu, Shaogen Gu, Xiyao Atianjoh, Fidelis E. Li, Zhen Fox, Brandon M. Pollock, David M. Tao, Yuan-Xiang Endothelin type A receptors mediate pain in a mouse model of sickle cell disease |
title | Endothelin type A receptors mediate pain in a mouse model of sickle cell disease |
title_full | Endothelin type A receptors mediate pain in a mouse model of sickle cell disease |
title_fullStr | Endothelin type A receptors mediate pain in a mouse model of sickle cell disease |
title_full_unstemmed | Endothelin type A receptors mediate pain in a mouse model of sickle cell disease |
title_short | Endothelin type A receptors mediate pain in a mouse model of sickle cell disease |
title_sort | endothelin type a receptors mediate pain in a mouse model of sickle cell disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029538/ https://www.ncbi.nlm.nih.gov/pubmed/29545351 http://dx.doi.org/10.3324/haematol.2017.187013 |
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