Although an increased and deeper innervation of painful and degenerate intervertebral discs (IVDs) has been reported, the mechanisms that regulate nerve growth into the IVD are largely unknown. In other tissues, proteoglycans have been found to act as nerve guidance molecules that, generally speaking, inhibit nerve growth. As disc degeneration is characterised by a loss of proteoglycans, we assessed the effects of IVD proteoglycans on nerve growth and guidance.

Using in vitro assays of nerve growth, we found that human disc proteoglycans inhibited nerve attachment, neurite extension and induced sensory growth cone turning in a dose-dependent manner. Digestions with chondroitinase ABC or keratinase abrogated these inhibitory effects. Proteoglycans of the anulus fibrosus were more inhibitory than those from the nucleus pulposus.

Disc proteoglycans inhibit nerve growth and this inhibitory activity may dependent on proteoglycan glycosylation and/or sulfation. A loss of proteoglycans from degenerative discs may therefore predispose the discs to nerve invasion.