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This study examined the association between progressive ectopic spine calcification in mice lacking equilibrative nucleoside transporter 1 (<jats:italic>ENT1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>), a preclinical model of DISH, and behavioral indicators of pain.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A longitudinal study design was used to assess radiating pain, axial discomfort, and physical function in wild-type and <jats:italic>ENT1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice at 2, 4, and 6\u00a0months. At endpoint, spinal cords were isolated for immunohistochemical analysis of astrocytes (GFAP), microglia (IBA1), and nociceptive innervation (CGRP).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Increased spine calcification in <jats:italic>ENT1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> 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 <jats:italic>ENT1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice at 6\u00a0months of age. Increased CGRP immunoreactivity was detected in the spinal cords of female and male <jats:italic>ENT1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice compared to wild-type. GFAP- and IBA1-immunoreactivity were increased in female <jats:italic>ENT1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice compared to wild-type, suggesting an increase in nociceptive innervation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>These data suggest that <jats:italic>ENT1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice experience axial discomfort and\/or stiffness and importantly that these features are detected during the early stages of spine calcification.\n<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-023-03053-3","type":"journal-article","created":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T05:01:41Z","timestamp":1682744501000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Stiffness and axial pain are associated with the progression of calcification in a mouse model of diffuse idiopathic skeletal hyperostosis"],"prefix":"10.1186","volume":"25","author":[{"given":"Dale E.","family":"Fournier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew A.","family":"Veras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney R.","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Quinonez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magali","family":"Millecamps","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura S.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryle A.","family":"S\u00e9guin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,4,29]]},"reference":[{"issue":"4","key":"3053_CR1","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1136\/ard.9.4.321","volume":"9","author":"J Forestier","year":"1950","unstructured":"Forestier J, Rotes-Querol J. 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