Painful,degenerating intervertebral discs up‐regulate neurite sprouting and CGRP through nociceptive factors |
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Authors: | Emerson Krock Derek H. Rosenzweig Anne‐Julie Chabot‐Doré Peter Jarzem Michael H. Weber Jean A. Ouellet Laura S. Stone Lisbet Haglund |
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Affiliation: | 1. Orthopeadic Research Laboratory, Division of Orthopedic Surgery, McGill University, , Montreal, QC, Canada;2. McGill Scoliosis and Spine Research Group, , Montreal, QC, Canada;3. Alan Edwards Centre for Research on Pain, , Montreal, QC, Canada;4. Integrated Program in Neuroscience, McGill University, , Montreal, QC, Canada;5. Department of Anesthesiology, McGill University, , Montreal, QC, Canada;6. Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, , Montreal, QC, Canada;7. Department of Faculty of Dentistry, McGill University, , Montreal, QC, Canada |
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Abstract: | Intervertebral disc degeneration (IVD) can result in chronic low back pain, a common cause of morbidity and disability. Inflammation has been associated with IVD degeneration, however the relationship between inflammatory factors and chronic low back pain remains unclear. Furthermore, increased levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are both associated with inflammation and chronic low back pain, but whether degenerating discs release sufficient concentrations of factors that induce nociceptor plasticity remains unclear. Degenerating IVDs from low back pain patients and healthy, painless IVDs from human organ donors were cultured ex vivo. Inflammatory and nociceptive factors released by IVDs into culture media were quantified by enzyme‐linked immunosorbent assays and protein arrays. The ability of factors released to induce neurite growth and nociceptive neuropeptide production was investigated. Degenerating discs release increased levels of tumour necrosis factor‐α, interleukin‐1β, NGF and BDNF. 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. |
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Keywords: | intervertebral disc degeneration discogenic pain human nerve growth factor
CGRP
inflammatory cytokines |
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