Fundamentals of intervertebral disc degeneration and related discogenic pain.

Lumbar intervertebral disc degeneration is thought to be the main cause of low back pain, although the mechanisms by which it occurs and leads to pain remain unclear. In healthy adult discs, vessels and nerves are present only in the outer layer of the annulus fibrosus and in the bony endplate. Animal models, and histological and biomechanical studies have shown that annulus tear or endplate injury is the initiating factor for painful disc degeneration. Injury to the disc triggers a local inflammatory repair response that activates nociceptors and promotes the synthesis of neuropeptides such as substance P and calcitonin gene-related peptide, by dorsal root ganglion neurons. These neuropeptides are transported to injured discs and act as pro-inflammatory molecules, promoting the production of an "inflammatory soup" by inducing vasodilatation and plasma extravasation as well as by promoting the release of chemical mediators from disc cells and infiltrating immune cells, causing neurogenic inflammation that leads to progressive disc degeneration and discogenic pain.