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Disc herniation may cause LBP and radicular pain, but not all LBP patients have disc herniation. Degenerated discs could be the source of pain, but not all degenerated discs are symptomatic. We previously found that disc degeneration and herniation accompanied by inflammation. We further found that anti\u2010inflammatory molecules blocked immune responses, alleviated IVD degeneration and pain. Based on our recent findings and the work of others, we hypothesize that immune system may play a prominent role in the production of disc herniation or disc degeneration associated pain. While the nucleus pulposus (NP) is an immune\u2010privileged organ, the damage of the physical barrier between NP and systemic circulation, or the innervation and vascularization of the degenerated NP, on one hand exposes NP as a foreign antigen to immune system, and on the other hand presents compression on the nerve root or dorsal root ganglion (DRG), which both elicit immune responses induced by immune cells and their mediators. The inflammation can remain for a long time at remote distance, with various types of cytokines and immune cells involved in this pain\u2010inducing process. In this review, we aim to revisit the autoimmunity of the NP, immune cell infiltration after break of physical barrier, the inflammatory activities in the DRG and the generation of pain. We also summarize the involvement of immune system, including immune cells and cytokines, in degenerated or herniated IVDs and affected DRG.<\/jats:p>","DOI":"10.1002\/jsp2.1196","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T07:50:44Z","timestamp":1647330644000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["The involvement of immune system in intervertebral disc herniation and degeneration"],"prefix":"10.1002","volume":"5","author":[{"given":"Fubiao","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Spine Surgery, The First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Department of Orthopaedics, Fujian Provincial Hospital Provincial Clinical Medical College of Fujian Medical University  Fuzhou Fujian 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