Cell Signaling Pathways Related to Pain Receptors in the Degenerated Disk

摘要

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. Keywords: nucleus pulposus, intervertebral disk degeneration, Wnt signal, low back pain, neurotrophic markers Low back pain represents a significant social and economic burden, including direct medical costs, lost production, and disability benefits, and lowers the quality of life of many individuals. 1 , 2 Low back pain is strongly associated with the intervertebral disk (IVD) degeneration, and IVD degeneration is also associated with sciatica and disk herniation or prolapse. It possibly adversely affects the behavior of other spinal structures such as muscles and ligaments. In the long term it can lead to spinal stenosis, a major cause of pain and disability in the elderly. Therefore, it follows that the suppression of IVD degeneration may limit the pain and disability associated with a range of pathologies of the back. Accordingly, clarification of the pathophysiology of IVD degeneration and its associated pain currently represents a major biomedical research priority. Much research is going on to understand IVD at a molecular level in hopes of creating clinically applicable options for treating IVD degeneration. Despite extensive study of the degenerative process in the IVD, the exact mechanism of diskogenic low back pain (IVD-related pain) has not been elucidated. In this review, we describe recent studies on diskogenic low back pain that have shed new light on the molecular mechanism and intracellular signaling pathways involved.