Cell Signaling Pathways Related to Pain Receptors in the Degenerated Disk

Many of the causes of low back pain are still unknown; sufficient evidence indicates that both degenerative and mechanical change within the intervertebral disk (IVD) is a relevant factor. This article reviews intracellular signaling pathways related to pain receptors in the degenerated IVD. Several reports have demonstrated the number of nerve fibers in the IVD was increased in degenerated disks. In recent years, some groups have reported that an increase in nerve fibers is associated with the presence of inflammatory mediators and/or neurotrophins in the IVD. Cell signaling events, which are regulated by inflammatory mediators and neurotrophins, must be identified to clarify the mechanism underlying low back pain. Major intracellular signaling pathways (nuclear factor kappa β, mitogen-activated protein kinases, and Wnts) potentially play vital roles in mediating the molecular events responsible for the initiation and progression of IVD degeneration. These signaling pathways may represent therapeutic targets for the treatment of IVD degeneration and its associated back pain.