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Despite extensive clinical and basic scientific research efforts, herniation etiopathogenesis, particularly its initiation and progression, is not well understood. Understanding herniation etiopathogenesis is essential for developing effective preventive measures and therapeutic interventions. Thus, this review seeks to provide a thorough overview of the advances in herniation\u2010oriented research, with a discussion on ongoing challenges and potential future directions for clinical, translational, and basic scientific investigations to facilitate innovative interdisciplinary research aimed at understanding herniation etiopathogenesis. Specifically, risk factors for herniation are identified and summarized, including familial predisposition, obesity, diabetes mellitus, smoking tobacco, selected cardiovascular diseases, disc degeneration, and occupational risks. Basic scientific experimental and computational research that aims to understand the link between excessive mechanical load, catabolic tissue remodeling due to inflammation or insufficient nutrient supply, and herniation, are also reviewed. Potential future directions to address the current challenges in herniation\u2010oriented research are explored by combining known progressive development in existing research techniques with ongoing technological advances. More research on the relationship between occupational risk factors and herniation, as well as the relationship between degeneration and herniation, is needed to develop preventive measures for working\u2010age individuals. Notably, researchers should explore using or modifying existing degeneration animal models to study herniation etiopathogenesis, as such models may allow for a better understanding of how to prevent mild\u2010to\u2010moderately degenerated discs from herniating.<\/jats:p>","DOI":"10.1002\/jsp2.1289","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T08:07:13Z","timestamp":1697616433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Understanding the etiopathogenesis of lumbar intervertebral disc herniation: From clinical evidence to basic scientific research"],"prefix":"10.1002","volume":"7","author":[{"given":"Minhao","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering University of California, Berkeley (UC Berkeley)  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alekos A.","family":"Theologis","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of California, San Francisco (UCSF)  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0746-1638","authenticated-orcid":false,"given":"Grace D.","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University of California, Berkeley (UC Berkeley)  Berkeley California USA"},{"name":"Department of Orthopaedic Surgery University of California, San Francisco (UCSF)  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12178-017-9441-4"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204428"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2021.07.005"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.0734"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.E.01273"},{"key":"e_1_2_7_7_1","unstructured":"BloomDE Boersch\u2010SupanA McGeeP SeikeA.Population aging: facts challenges and responses. 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