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IVD degeneration and associated spinal pain is a complex multifactorial process, its complexity poses difficulties in the selection of the most appropriate therapeutic target to focus on of many potential candidates in the formulation of strategies to alleviate pain perception and to effect disc repair and regeneration and the prevention of associated neuropathic and nociceptive pain. Nerve ingrowth and increased numbers of nociceptors and mechanoreceptors in the degenerate IVD are mechanically stimulated in the biomechanically incompetent abnormally loaded degenerate IVD leading to increased generation of low back pain. Maintenance of a healthy IVD is, thus, an important preventative measure that warrants further investigation to preclude the generation of low back pain. Recent studies with growth and differentiation factor 6 in IVD puncture and multi\u2010level IVD degeneration models and a rat xenograft radiculopathy pain model have shown it has considerable potential in the prevention of further deterioration in degenerate IVDs, has regenerative properties that promote recovery of normal IVD architectural functional organization and inhibits the generation of inflammatory mediators that lead to disc degeneration and the generation of low back pain. Human clinical trials are warranted and eagerly anticipated with this compound to assess its efficacy in the treatment of IVD degeneration and the prevention of the generation of low back pain.<\/jats:p>","DOI":"10.1002\/jsp2.1231","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T07:41:15Z","timestamp":1668498075000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":133,"title":["Intervertebral disc degeneration and how it leads to low back pain"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1037-8421","authenticated-orcid":false,"given":"Ashish D.","family":"Diwan","sequence":"first","affiliation":[{"name":"Spine Service, Department of Orthopaedic Surgery, St. George &amp; Sutherland Clinical School University of New South Wales Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9237-0524","authenticated-orcid":false,"given":"James","family":"Melrose","sequence":"additional","affiliation":[{"name":"Raymond Purves Bone and Joint Research Laboratory Kolling Institute, Sydney University Faculty of Medicine and Health, Northern Sydney Area Health District, Royal North Shore Hospital Sydney New South Wales Australia"},{"name":"Graduate School of Biomedical Engineering The University of New South Wales Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,14]]},"reference":[{"key":"e_1_2_15_2_1","first-page":"1116","article-title":"Low back pain (chronic)","volume":"2010","author":"Chou R","year":"2010","journal-title":"BMJ Clin Evid"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.2009.tb02527.x"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-160-11-201406030-01006"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61729-2"},{"key":"e_1_2_15_6_1","first-page":"671","article-title":"Low back pain","volume":"81","author":"Ehrlich G","year":"2003","journal-title":"Bull World Health Organ"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(99)00187-6"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/101053950301500202"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2016.07.013"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/2192568218770769"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e31815b64d2"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-019-6465-2"},{"key":"e_1_2_15_13_1","volume-title":"Some economic consequences of global aging: A discussion note for the World Bank. 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