Intervertebral disc (IVD) degeneration is one of the major causes of low back pain (LBP). Due to the complexity of spinal pain syndromes, it is often difficult to determine the extent of the IVD’s contribution to the genesis of spinal pain. Inflammatory response to IVD’ injury has been acknowledged to be important in the process of disc degeneration and may play an important role in pain generation. In this article, the inflammatory mechanisms of LBP will be discussed with special focus on interactions between inflammatory mediators and IVD biomechanics. Tumor necrosis factor-α (TNF-α) is a key mediator of inflammatory reactions in the pathogenesis of degenerative disk disease. The role of TNF-α inhibitors as a potential target of therapeutic interventions in prevention of neuronal damage and neuroprotection in LBP is discussed.