{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T13:56:13Z","timestamp":1778939773065,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:00:00Z","timestamp":1686268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001702","name":"AO Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001702","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Mechanical overloading can trigger a degenerative\u2010like cascade in an organ culture of intervertebral disc (IVD). Whether the overloaded IVD can influence the activation of nociceptors (i.e., the damage sensing neurons) remains unknown. The study aims to investigate the influence of overloaded IVD conditioned medium (CM) on the activation of nociceptors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the static loading regime, force\u2010controlled loading of 0.2\u2009MPa for 20\u2009h\/day representing \u201clong\u2010term sitting and standing\u201d was compared with a displacement\u2010controlled loading maintaining original IVD height. In the dynamic loading regime, high\u2010frequency\u2010intensity loading representing degenerative \u201cwear and tear\u201d was compared with a lower\u2010frequency\u2010intensity loading. CM of differently loaded IVDs were collected to stimulate the primary bovine dorsal root ganglion (DRG) cultures. Calcium imaging (Fluo\u20104) and calcitonin gene\u2010related peptide (CGRP) immunofluorescent labeling were jointly used to record the calcium flickering in CGRP(+) nociceptors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Force\u2010controlled loading led to a higher IVD cell death compared to displacement\u2010controlled loading. Both static and dynamic overloading (force\u2010controlled and high\u2010frequency\u2010intensity loadings) elevated the frequency of calcium flickering in the subsurface space of CGRP(+) nociceptors compared to their mild loading counterparts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In the organ culture system, IVD overloading mediated an altered IVD\u2010nociceptor communication suggesting a biological mechanism associated with discogenic pain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.1267","type":"journal-article","created":{"date-parts":[[2023,6,10]],"date-time":"2023-06-10T00:09:42Z","timestamp":1686355782000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The influence of intervertebral disc overloading on nociceptor calcium flickering"],"prefix":"10.1002","volume":"6","author":[{"given":"Jan","family":"Gewiess","sequence":"first","affiliation":[{"name":"AO Research Institute, AO Foundation  Davos Switzerland"},{"name":"Department of Orthopaedic Surgery and Traumatology Inselspital, Bern University Hospital, University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janick","family":"Eglauf","sequence":"additional","affiliation":[{"name":"AO Research Institute, AO Foundation  Davos Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid","family":"Soubrier","sequence":"additional","affiliation":[{"name":"AO Research Institute, AO Foundation  Davos Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9552-3653","authenticated-orcid":false,"given":"Sibylle","family":"Grad","sequence":"additional","affiliation":[{"name":"AO Research Institute, AO Foundation  Davos Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0262-1412","authenticated-orcid":false,"given":"Mauro","family":"Alini","sequence":"additional","affiliation":[{"name":"AO Research Institute, AO Foundation  Davos Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Peroglio","sequence":"additional","affiliation":[{"name":"\u00c9cole des Mines de Saint\u2010\u00c9tienne Univ. 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