Introduction: Intervertebral disc (IVD) degeneration is a major underlying factor in the pathogenesis of chronic low back pain. The healthy IVD is both avascular and aneural, however during symptomatic degeneration there is ingrowth of nociceptive nerve fibres and blood vessels into proximal regions of the IVD. Semaphorin 3A (sema3A) is an axonal guidance molecule with the ability to repel nerves. This study aimed to identify whether class 3 semaphorins were expressed by cells of the IVD and addresses the hypothesis that they may play a role in repelling axons surrounding the healthy disc thus maintaining its aneural condition.

Methods: Forty human IVD samples were investigated using RT-PCR and immunohistochemistry to identify the expression of sema3A, 3F and their receptors; neuropilins (1 & 2) and plexins (A1-4). Serial sections were stained for PGP9.5 and CD31 to correlate semaphorin expression with nerve and blood vessel ingrowth respectively.

Results: Sema3A protein, localised primarily to the OAF, was expressed highly in the healthy disc. In degenerate samples sema3A expression decreased significantly in this region, although chondrocyte clusters within the degenerate NP exhibited strong immunopositivity. mRNA for sema3A receptors was also identified in healthy and degenerate tissues. CD31 and PGP9.5 were expressed most highly in degenerate tissues correlating with low expression of sema3A.

Conclusions: This study is the first to establish the expression of semaphorins and their receptors in the human IVD with a decrease seen in the degenerate symptomatic IVD. Sema3A may therefore, amongst other roles, act as a ‘barrier’ to neuronal ingrowth into the healthy disc.

Conflicts of Interest: None declared

Sources of Funding: Arthritis Research Campaign