Targeting the nuclear factor kappa B pathway for the medical management of intervertebral disc degeneration

Intervertebral disc degeneration (IVDD), a key contributor to low back pain, is driven by multiple predisposing factors, such as oxidative stress, inflammation, and mechanical stress, among others, severely impacting patients' quality of life. The nuclear factor kappa B (NF-κB) signaling pathway is crucial in the development of IVDD. This review examines the mechanisms of NF-κB activation, focusing on classical and non-classical pathways and their roles in IVDD progression. A variety of therapeutic approaches have been developed to target the NF-κB pathway, including NSAIDs, proteins, non-coding RNAs, hormones, natural chemicals, and sophisticated biomaterials. These interventions inhibit NF-κB activation, alleviating apoptosis, extracellular matrix (ECM) imbalance, and inflammation in the nucleus pulposus. In this review, we not only focus on summarizing the emerging biomaterials and natural medicines targeting NF-κB to treat IVDD in recent years, but also discuss the current challenges, such as limited drug delivery to the avascular disc and the need to elucidate non-classical NF-κB pathways, and outline future directions for clinical translation. These insights inject new vitality into the treatment of IVDD. Despite progress in targeting NF-κB, significant challenges remain in translating these therapies into clinical practice. Further exploring the potential of targeting the NF-κB pathway in the treatment of IVDD can promote the development of new IVDD treatments.