{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:18:46Z","timestamp":1792811926157,"version":"4.5.0"},"reference-count":168,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Discogenic back pain, a subset of chronic back pain, is caused by intervertebral disc (IVD) degeneration, and imparts a notable socioeconomic health burden on the population. However, degeneration by itself does not necessarily imply discogenic pain. In this review, we highlight the existing literature on the pathophysiology of discogenic back pain, focusing on the biomechanical and biochemical steps that lead to pain in the setting of IVD degeneration. Though the pathophysiology is incompletely characterized, the current evidence favors a framework where degeneration leads to IVD inflammation, and subsequent immune milieu recruitment. Chronic inflammation serves as a basis of penetrating neovascularization and neoinnervation into the IVD. Hence, nociceptive sensitization emerges, which manifests as discogenic back pain. Recent studies also highlight the complimentary roles of low virulence infections and central nervous system (CNS) metabolic state alteration. Targeted therapies that seek to disrupt inflammation, angiogenesis, and neurogenic pathways are being investigated. Regenerative therapy in the form of gene therapy and cell-based therapy are also being explored.<\/jats:p>","DOI":"10.3390\/jcm12216907","type":"journal-article","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T09:28:13Z","timestamp":1698917293000},"page":"6907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Updates on Pathophysiology of Discogenic Back Pain"],"prefix":"10.3390","volume":"12","author":[{"given":"Rohan","family":"Jha","sequence":"first","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7814-3867","authenticated-orcid":false,"given":"Joshua D.","family":"Bernstock","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1769-5120","authenticated-orcid":false,"given":"Joshua I.","family":"Chalif","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha E.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saksham","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8180-8578","authenticated-orcid":false,"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S0140-6736(99)01312-4","article-title":"Epidemiological features of chronic low-back pain","volume":"354","author":"Andersson","year":"1999","journal-title":"Lancet"},{"key":"ref_2","unstructured":"Global Burden of Disease Study 2013 Collaborators (2015). 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