{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:48:09Z","timestamp":1783637289899,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006380","name":"Department of Veterans Affairs Rehabilitation Research and Development Service","doi-asserted-by":"publisher","award":["I01 RX002274"],"award-info":[{"award-number":["I01 RX002274"]}],"id":[{"id":"10.13039\/100006380","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006380","name":"Department of Veterans Affairs Rehabilitation Research and Development Service","doi-asserted-by":"publisher","award":["I50 RX004845"],"award-info":[{"award-number":["I50 RX004845"]}],"id":[{"id":"10.13039\/100006380","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006380","name":"Department of Veterans Affairs Rehabilitation Research and Development Service","doi-asserted-by":"publisher","award":["IK6 RX003416"],"award-info":[{"award-number":["IK6 RX003416"]}],"id":[{"id":"10.13039\/100006380","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIH\/NIAMS R01 AR083007"],"award-info":[{"award-number":["NIH\/NIAMS R01 AR083007"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016787","name":"Penn Center for Musculoskeletal Disorders","doi-asserted-by":"crossref","award":["NIH\/NIAMS P30 AR069619"],"award-info":[{"award-number":["NIH\/NIAMS P30 AR069619"]}],"id":[{"id":"10.13039\/100016787","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Intervertebral disc degeneration (IVDD) initiates a cascade of structural and biological changes that compromise mechanical function, often leading to chronic pain. While small animal models have provided insight into inflammatory and nociceptive mechanisms of IVDD, translational studies require large animal models that more closely replicate human spine anatomy and physiology. This study induced cervical disc degeneration via intradiscal chondroitinase ABC (ChABC) injection in a large animal model and evaluated the associated disc pathology and neuroinflammatory responses across IVDs and within spinal cord and dorsal root ganglia (DRG) tissues. Results confirmed structural degeneration at ChABC-injected levels and revealed additional evidence of adjacent segment degeneration. Neuroinflammatory analyses revealed innervation, via deposition of PGP9.5 and NFH, throughout both ChABC-injected and adjacent IVDs. Monocyte markers were significantly increased in ChABC-degenerated IVDs. Across experimental groups, the level of monocyte (Ly6C) and macrophage (CD68) markers correlated with worsened histological scores and with reduced mechanical integrity. Similarly, increased production of the neuropeptide, Substance P, in IVDs was significantly positively correlated with compromised IVD mechanical function. Finally, we observed elevated production of the microglia marker, Iba1, and Substance P production in the spinal cord, with similar trends in DRGs, in degenerative spines. By establishing quantitative relationships between disc pathology, immune responses, and neural activation, this work established possible disease-contributing neuroinflammatory activation and further validated a clinically relevant model for preclinical evaluation of regenerative and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cells15030286","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T10:48:01Z","timestamp":1770115681000},"page":"286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuroimmune Activation in a Goat Model of Intervertebral Disc Degeneration"],"prefix":"10.3390","volume":"15","author":[{"given":"Janai A.","family":"Augustin","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Translational Musculoskeletal Research Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"},{"name":"Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8504-7980","authenticated-orcid":false,"given":"Kevin G.","family":"Burt","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Translational Musculoskeletal Research Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"},{"name":"CReATE Motion Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Barrett","sequence":"additional","affiliation":[{"name":"Translational Musculoskeletal Research Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"},{"name":"Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0016-3267","authenticated-orcid":false,"given":"Matthew","family":"Fainor","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Translational Musculoskeletal Research Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna S.","family":"Orozco","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Translational Musculoskeletal Research Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4340-8212","authenticated-orcid":false,"given":"Thomas P.","family":"Schaer","sequence":"additional","affiliation":[{"name":"CReATE Motion Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"},{"name":"Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey E.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Translational Musculoskeletal Research Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Mauck","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Translational Musculoskeletal Research Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"},{"name":"Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"CReATE Motion Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-6606","authenticated-orcid":false,"given":"Sarah E.","family":"Gullbrand","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Translational Musculoskeletal Research Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"},{"name":"CReATE Motion Center, CMC Veterans Affairs Medical Center, Philadelphia, PA 19104, 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