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IVD degeneration affects the structure and function of both the disc and the innervating dorsal root ganglion (DRG) neurons. Preclinical animal models are necessary for elucidating the mechanisms of IVD degeneration (IVDD) and the pain signaling pathways involved in discogenic back pain. The chondrodystrophic (CD) dog exhibits similar characteristics to the clinical population affected by IVDD\u2010associated LBP. However, further investigation of the translational tools to study these conditions and the efficacy of novel treatments is needed in this canine model. The objectives of the present study are to: (1) assess the changes in the structure and function of the IVD and DRG, including pain behaviors, in response to injury using a comprehensive set of outcome measures and (2) evaluate the efficacy of potential therapeutics in mitigating these pathologic changes due to injury in the CD canine model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Retired female research beagles underwent spinal surgery where T11\/T12, T12\/T13, and T13\/L1 IVDs were identified and punctured with a needle containing either a protease\u2010activated receptor 2 antagonist (PAR2A) and cromolyn sodium (CS) solution (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20093) or phosphate\u2010buffered saline (PBS) (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20093). Pain phenotyping and related outcomes were assessed longitudinally or at the 12\u2010week endpoint via RNA\u2010seq on the DRG, von Frey analysis, FitBark activity, and C\u2010reactive protein plasma levels. Changes in the structure\/function of the IVD were assessed via MRI, mechanics, dimethylmethylene blue assay (DMMB), histological staining using picrosirius red\/alcian blue (PR\/AB) and fluoroscopy, and electrophysiology on the DRG neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We evaluated a comprehensive series of outcome measures to determine the effects of IVD injury on the structure\/function of the canine IVD and DRG, and pain in the in\u00a0vivo CD dog model of IVDD and back pain. Specifically, we established methods to obtain high\u2010quality messenger RNA from canine DRGs to perform bulk RNA\u2010seq. We demonstrated that injury to the disc resulted in significant upregulation of inflammatory and pain\u2010signaling genes, and downregulation of developmental genes in the adjacent innervating DRG neurons. Additionally, we isolated and cultured viable neurons from canine DRGs and found through whole\u2010cell patch\u2010clamp that DRGs innervating the injured disc demonstrated altered voltage\u2010gated sodium channel activity compared to controls. Using T2\u2010weighted MRI, we demonstrated that relaxation time in punctured discs was reduced in four out of the six dogs compared to internal control discs, indicating potential compositional changes in these injured IVDs. No significant effect of PAR2A and CS treatment was observed in this small cohort and warrants further investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study evaluated a rigorous series of outcome measures to determine the effects of IVD injury on the disc joint and pain in a CD canine in\u00a0vivo model of back pain. This was the first study to investigate the effects of disc injury on canine DRG transcriptome and whole\u2010cell patch clamping on canine DRG neurons. Results support the CD dog as a clinically relevant translational model for studying IVDD and LBP, and for evaluating the potential efficacy of novel therapeutics in mitigating the changes associated with these conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70082","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T15:54:17Z","timestamp":1752508457000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chondrodystrophic Dogs as a Preclinical Large Animal Model of Discogenic Back Pain"],"prefix":"10.1002","volume":"8","author":[{"given":"Mary K.","family":"Heimann","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8807-2348","authenticated-orcid":false,"given":"Shirley 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