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Signaling pathways involved in painful IVD degeneration Various pathways, such as the nuclear factor kappa-B (NF-B) and mitogen-activated protein kinase (MAPK) pathways, have been found to play essential roles in the production of inflammatory factors and catabolism of ECM in the IVD, 128 and increasing evidence supports the importance of these signaling pathways and Toll-like receptor (TLR) signaling in painful disc diseases, as summarized in Fig

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