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: Calcitonin gene-related peptide is a neurotransmitter that acts as a pain modulator and increased production can cause hyperexcitability and sensitization. To determine the effect of degenerating, painful IVD media on CGRP expression, DRG neurons were exposed to this media and compared healthy pain-free IVD media. After 48 hrs, neuronal cultures were analysed for the expression of the general neuronal marker PGP 9.5 (green) and CGRP (red; Fig.3A). The proportion of neurons that showed CGRP expression was analysed for each treatment. 16 ± 1% of untreated neurons, and 30 ± 2% of 10 ng/ml NGF-treated neurons expressed CGRP. Similar to untreated controls, 18 ± 2% of neurons cultured in healthy, pain-free IVD media expressed CGRP. Similar to NGF-treated controls, 29 ± 2% of neurons cultured in degenerating, painful IVD media were CGRP immunoreactive. 10 ng/ml NGF-treated neurons had a significantly higher percentage of CGRP-immunoreactive cells compared to untreated controls (P = 0.0045). There was no difference in CGRP immunoreactivity between non-treated and healthy, pain-free media groups (P = 0.9999) or between NGF-treated and degenerating, painful media groups (P > 0.9999). A significantly greater proportion of cells cultured in degenerating, painful IVD were CGRP immunoreactive compared to neurons cultured in healthy, pain-free IVD media (P = 0.007, Fig.3B).
Affiliation: Orthopeadic Research Laboratory, Division of Orthopedic Surgery, McGill University, Montreal, QC, Canada; McGill Scoliosis and Spine Research Group, Montreal, QC, Canada.