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
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Mentions: As degenerating, painful IVDs release increased amounts of NGF and BDNF ex vivo, the conditioned media were tested for the ability to stimulate neurite growth in PC12 cells. After 48 hrs of culture, 20 ± 3% of untreated cells, 78 ± 4% of NGF-treated cells, 29 ± 2% of cells cultured in healthy, pain-free IVD media and 64 ± 2% of cells cultured in degenerating, painful IVDs had neurites (Fig.2A and B; n = 6 IVDs for each conditioned media group). A significantly greater proportion of cells treated with NGF extended neurites when compared to untreated cells (P < 0.0001). There was no significant difference in the proportion of cells with neurites between untreated and healthy IVD media groups (P = 0.25). NGF cultures had a greater proportion of cells compared to degenerating media groups (P < 0.01). However, degenerating, painful IVD media induced neurite sprouting in a significantly greater percentage of cells compared to cells cultured in healthy, pain-free IVD media (P = <0.0001) (Fig.2) indicating that painful, degenerating IVDs produce factors that promote neurite growth.
Affiliation: Orthopeadic Research Laboratory, Division of Orthopedic Surgery, McGill University, Montreal, QC, Canada; McGill Scoliosis and Spine Research Group, Montreal, QC, Canada.