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This review systematically delineates the pathological basis of the HIZ and provides a comprehensive dissection of the molecular pathways it shares with LDD. while also summarizing recent advancements in artificial intelligence and multimodal imaging for enhancing HIZ detection and characterization. The HIZ is positioned as a \u201cdynamic inflammatory hub\u201d characterized by vascularized granulation tissue infiltration, nerve ingrowth, and a localized chronic inflammatory response following annular fissures. The molecular pathology involves a self\u2010perpetuating \u201cinflammation\u2010matrix degradation\u201d vicious cycle driven by cytokines (e.g., TNF\u2010\u03b1, IL\u20101\u03b2) and matrix\u2010degrading enzymes (e.g., MMPs, ADAMTS), underscoring its central role in the chronicization of discogenic low back pain (DLBP). Although the HIZ exhibits high specificity for diagnosing DLBP, its utility is constrained by limited sensitivity, false positives, and a notable dissociation from clinical symptoms. Furthermore, a stratified and diversified therapeutic blueprint is outlined, ranging from physical ablation and nucleus pulposus replacement to biologic agents (e.g., platelet\u2010rich plasma), regenerative medicine (e.g., stem cell therapy), and cutting\u2010edge nanotechnologies. Moving beyond conventional morphology to integrate advanced diagnostic technologies is imperative. Looking forward, integrating molecular imaging, single\u2010cell omics, and precision medicine strategies to target the HIZ microenvironment offers a promising new paradigm for disrupting the \u201cinflammation\u2010degeneration\u2010pain\u201d cycle, restoring disc homeostasis, and achieving precise diagnosis and treatment of DLBP.<\/jats:p>","DOI":"10.1111\/os.70389","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T08:52:51Z","timestamp":1784969571000},"page":"1804-1818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The High\u2010Intensity Zone: A Dynamic Inflammatory Hub in Lumbar Disc Degeneration"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0678-6253","authenticated-orcid":false,"given":"Qi","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Radiology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"College of Medicine, Hubei Minzu University  Enshi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Radiology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"College of Medicine, Hubei Minzu University  Enshi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0504-9303","authenticated-orcid":false,"given":"Weijian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Radiology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Department of Orthopedics Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Chest Hospital of Tianjin University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liling","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Medicine, Hubei Minzu University  Enshi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyao","family":"Pei","sequence":"additional","affiliation":[{"name":"College of Business, Guilin Institute of Information and Technology  Guilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Radiology Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1911"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-005-0892-8"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S332509"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0160111"},{"key":"e_1_2_17_6_1","unstructured":"\u201cLumbar Disc High\u2010Intensity Zone: The Value and Significance of Provocative Discography in the Determination of the Discogenic Pain Source 2000\u201d."},{"issue":"6","key":"e_1_2_17_7_1","first-page":"965","article-title":"\u2018Stress\u2019 Distributions Inside Intervertebral Discs","volume":"78","author":"Adams M. 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