Painful, degenerating intervertebral discs up-regulate neurite sprouting and CGRP through nociceptive factors.
Bottom Line: Factors released by degenerating IVDs increased neurite growth and calcitonin gene-related peptide expression, both of which were blocked by anti-NGF treatment.Furthermore, protein arrays found increased levels of 20 inflammatory factors, many of which have nociceptive effects.Our results demonstrate that degenerating and painful human IVDs release increased levels of NGF, inflammatory and nociceptive factors ex vivo that induce neuronal plasticity and may actively diffuse to induce neo-innervation and pain in vivo.
Affiliation: Orthopeadic Research Laboratory, Division of Orthopedic Surgery, McGill University, Montreal, QC, Canada; McGill Scoliosis and Spine Research Group, Montreal, QC, Canada.Show MeSH
Related in: MedlinePlus
Mentions: Although the degenerating IVD media induced neurite growth, the same concentration range of NGF alone was insufficient. Therefore, protein arrays were used to identify potential cooperative factors . Degenerating and painful IVDs released significantly higher levels of 20 of these factors (Fig.5A-D, Table1). Fifteen factors had a P value below 0.01 (GCSF, GM-CSF, IFN-γ, IL-2, IL-3, IL-5, IL-6, IL-7, IL-15, CCL2, CCL7, CCL8, MIG, RANTES and TNF-β), and five factors had a P value between 0.01 and 0.05 (IL-1α, IL-13, TNF-α, GRO and CXCL1). There was no difference in the relative quantities of IL-8, IL-10 and TGF-β1 between the two groups (Fig.5D, Table1). The relative mean quantities and a summary of previous studies implicating specific factors with either degenerating IVDs and/or pain are listed in Table1. Of particular interest are IFN-γ, IL-6, CCL2 and CXCL1 because of their suggested role in IVD degeneration, neuronal sensitization and pain [10,31–37]. Figure5E shows the individual donor variation in these factors. IFN-γ and CXCL1 showed a fairly large donor variation especially in the degenerate samples whereas the levels of IL-6 and CCL2 were much more homogeneous in their expression levels within each of the two groups.
Affiliation: Orthopeadic Research Laboratory, Division of Orthopedic Surgery, McGill University, Montreal, QC, Canada; McGill Scoliosis and Spine Research Group, Montreal, QC, Canada.