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Local elevated neurotrophin levels will stimulate sprouting and innervation of sensory neurons. Furthermore, sprouted sensory nerves that are directly connected to adjacent dorsal root ganglia have shown to increase microglia activation, contributing to the maintenance and chronification of pain. Current pain treatments have shown to be insufficient or inadequate for long\u2010term usage. Furthermore, most therapeutic approaches aimed to target the underlying pathogenesis of disc degeneration focus on repair and regeneration and neglect chronic pain. How biomolecular therapies influence the degenerative IVD environment, pain signaling cascades, and innervation and excitability of the sensory neurons often remains unclear. This review addresses the relatively underexplored area of chronic pain treatment for CD\u2010LBP and summarizes effects of therapies aimed for CD\u2010LBP with special emphasis on chronic pain. Approaches based on blocking pro\u2010inflammatory mediators or neurotrophin activity have been shown to hamper neuronal ingrowth into the disc. Furthermore, the tissue regenerative and neuro inhibitory properties of extracellular matrix components or transplanted mesenchymal stem cells are potentially interesting biomolecular approaches to not only block IVD degeneration but also impede pain sensitization. At present, most biomolecular therapies are based on acute IVD degeneration models and thus do not reflect the real clinical chronic pain situation in CD\u2010LBP patients. Future studies should aim at investigating the effects of therapeutic interventions applied in chronic degenerated discs containing established sensory nerve ingrowth. The in\u2010depth understanding of the ramifications from biomolecular therapies on pain (chronification) pathways and pain relief in CD\u2010LBP could help narrow the gap between the pre\u2010clinical bench and clinical bedside for novel CD\u2010LBP therapeutics and optimize pain treatment.<\/jats:p>","DOI":"10.1002\/jsp2.1345","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T04:51:48Z","timestamp":1723006308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Biomolecular therapies for chronic discogenic low back pain: A narrative review"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2508-3610","authenticated-orcid":false,"given":"Imke","family":"Rudnik\u2010Jansen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Management Maastricht University Medical Center (MUMC+)  Maastricht the 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