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Stiffness and axial pain are associated with the progression of calcification in a mouse model of diffuse idiopathic skeletal hyperostosis
BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by progressive calcification of spinal tissues; however, the impact of calcification on pain and function is poorly understood. This study examined the association between progressive ectopic spine calcification in mice lac...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148510/ https://www.ncbi.nlm.nih.gov/pubmed/37120576 http://dx.doi.org/10.1186/s13075-023-03053-3 |
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author | Fournier, Dale E. Veras, Matthew A. Brooks, Courtney R. Quinonez, Diana Millecamps, Magali Stone, Laura S. Séguin, Cheryle A. |
author_facet | Fournier, Dale E. Veras, Matthew A. Brooks, Courtney R. Quinonez, Diana Millecamps, Magali Stone, Laura S. Séguin, Cheryle A. |
author_sort | Fournier, Dale E. |
collection | PubMed |
description | BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by progressive calcification of spinal tissues; however, the impact of calcification on pain and function is poorly understood. This study examined the association between progressive ectopic spine calcification in mice lacking equilibrative nucleoside transporter 1 (ENT1(−/−)), a preclinical model of DISH, and behavioral indicators of pain. METHODS: A longitudinal study design was used to assess radiating pain, axial discomfort, and physical function in wild-type and ENT1(−/−) mice at 2, 4, and 6 months. At endpoint, spinal cords were isolated for immunohistochemical analysis of astrocytes (GFAP), microglia (IBA1), and nociceptive innervation (CGRP). RESULTS: Increased spine calcification in ENT1(−/−) mice was associated with reductions in flexmaze exploration, vertical activity in an open field, and self-supporting behavior in tail suspension, suggesting flexion-induced discomfort or stiffness. Grip force during the axial stretch was also reduced in ENT1(−/−) mice at 6 months of age. Increased CGRP immunoreactivity was detected in the spinal cords of female and male ENT1(−/−) mice compared to wild-type. GFAP- and IBA1-immunoreactivity were increased in female ENT1(−/−) mice compared to wild-type, suggesting an increase in nociceptive innervation. CONCLUSION: These data suggest that ENT1(−/−) mice experience axial discomfort and/or stiffness and importantly that these features are detected during the early stages of spine calcification. |
format | Online Article Text |
id | pubmed-10148510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101485102023-04-30 Stiffness and axial pain are associated with the progression of calcification in a mouse model of diffuse idiopathic skeletal hyperostosis Fournier, Dale E. Veras, Matthew A. Brooks, Courtney R. Quinonez, Diana Millecamps, Magali Stone, Laura S. Séguin, Cheryle A. Arthritis Res Ther Research BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by progressive calcification of spinal tissues; however, the impact of calcification on pain and function is poorly understood. This study examined the association between progressive ectopic spine calcification in mice lacking equilibrative nucleoside transporter 1 (ENT1(−/−)), a preclinical model of DISH, and behavioral indicators of pain. METHODS: A longitudinal study design was used to assess radiating pain, axial discomfort, and physical function in wild-type and ENT1(−/−) mice at 2, 4, and 6 months. At endpoint, spinal cords were isolated for immunohistochemical analysis of astrocytes (GFAP), microglia (IBA1), and nociceptive innervation (CGRP). RESULTS: Increased spine calcification in ENT1(−/−) mice was associated with reductions in flexmaze exploration, vertical activity in an open field, and self-supporting behavior in tail suspension, suggesting flexion-induced discomfort or stiffness. Grip force during the axial stretch was also reduced in ENT1(−/−) mice at 6 months of age. Increased CGRP immunoreactivity was detected in the spinal cords of female and male ENT1(−/−) mice compared to wild-type. GFAP- and IBA1-immunoreactivity were increased in female ENT1(−/−) mice compared to wild-type, suggesting an increase in nociceptive innervation. CONCLUSION: These data suggest that ENT1(−/−) mice experience axial discomfort and/or stiffness and importantly that these features are detected during the early stages of spine calcification. BioMed Central 2023-04-29 2023 /pmc/articles/PMC10148510/ /pubmed/37120576 http://dx.doi.org/10.1186/s13075-023-03053-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Fournier, Dale E. Veras, Matthew A. Brooks, Courtney R. Quinonez, Diana Millecamps, Magali Stone, Laura S. Séguin, Cheryle A. Stiffness and axial pain are associated with the progression of calcification in a mouse model of diffuse idiopathic skeletal hyperostosis |
title | Stiffness and axial pain are associated with the progression of calcification in a mouse model of diffuse idiopathic skeletal hyperostosis |
title_full | Stiffness and axial pain are associated with the progression of calcification in a mouse model of diffuse idiopathic skeletal hyperostosis |
title_fullStr | Stiffness and axial pain are associated with the progression of calcification in a mouse model of diffuse idiopathic skeletal hyperostosis |
title_full_unstemmed | Stiffness and axial pain are associated with the progression of calcification in a mouse model of diffuse idiopathic skeletal hyperostosis |
title_short | Stiffness and axial pain are associated with the progression of calcification in a mouse model of diffuse idiopathic skeletal hyperostosis |
title_sort | stiffness and axial pain are associated with the progression of calcification in a mouse model of diffuse idiopathic skeletal hyperostosis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148510/ https://www.ncbi.nlm.nih.gov/pubmed/37120576 http://dx.doi.org/10.1186/s13075-023-03053-3 |
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