Sources of lumbar back pain during aging and potential therapeutic targets

Lumbar back pain during aging is a major clinical problem, the origins and underlying mechanisms of which are challenging to study. Degenerative changes occur in various parts of the functional spinal unit, such the vertebral endplate and intervertebral disc. The homeostasis of these structural components is regulated by signaling molecules, such as transforming growth factor-β and parathyroid hormone. Previous efforts to understand sources of lumbar back pain focused on sensory innervation in the degenerative intervertebral disc, but intervertebral disc degeneration is frequently asymptomatic. An in vivo mouse model of lumbar spine aging and degeneration, combined with genetic technology, has identified endplate innervation as a major source of lumbar back pain and a potential therapeutic target. In this review, we consider how each structural component of the functional spinal unit contributes to lumbar back pain, how the homeostasis of each component is regulated, and how these findings can be used to develop potential therapies.