Limits...
Painful, degenerating intervertebral discs up-regulate neurite sprouting and CGRP through nociceptive factors.

Krock E, Rosenzweig DH, Chabot-Doré AJ, Jarzem P, Weber MH, Ouellet JA, Stone LS, Haglund L - J. Cell. Mol. Med. (2014)

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.

View Article: PubMed Central - PubMed

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

Tumour necrosis factor-α (TNF-α; A), nerve growth factor (NGF; B) and brain derived neurotrophic factor (BDNF; C) mean concentrations in media from healthy pain-free or degenerating, painful intervertebral disc (IVDs). n = 8 in degenerate, painful group and n = 11 in healthy, pain-free group for TNF-α and NGF ±95% CI, unpaired t-test. n = 7 in degenerating, painful group and n = 9 in healthy, pain-free group for BDNF, ±95% CI, Mann–Whitney test. **P < 0.01, ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4508160&req=5

fig01: Tumour necrosis factor-α (TNF-α; A), nerve growth factor (NGF; B) and brain derived neurotrophic factor (BDNF; C) mean concentrations in media from healthy pain-free or degenerating, painful intervertebral disc (IVDs). n = 8 in degenerate, painful group and n = 11 in healthy, pain-free group for TNF-α and NGF ±95% CI, unpaired t-test. n = 7 in degenerating, painful group and n = 9 in healthy, pain-free group for BDNF, ±95% CI, Mann–Whitney test. **P < 0.01, ***P < 0.001.

Mentions: As isolated IVD cells can release inflammatory and nuerotrophic factors [27,28] and histological analyses of degenerate tissue have confirmed this [8,29], we quantified the ability of degenerating IVDs to actively release these factors ex vivo into culture media. Intervertebral discs was cultured on a volume per weight. ELISA analysis revealed that degenerating, painful IVDs released a significantly greater amount of TNF-α (138.3 ± 24.7 pg/ml, P = 0.01, Fig.1A) compared to healthy, pain-free IVDs (69.2 ± 22.6 pg/ml). NGF released at a significantly greater amount by degenerating, painful IVDs (44.2 ± 6.5 pg/ml, P < 0.001, Fig.1B) compared to healthy, pain-free IVDs (12.5 ± 4.5 pg/ml). Brain derived neurotrophic factor was significantly higher in the media from degenerating, painful IVDs (1.54 ± 0.026 ng/ml, P = 0.004, Fig.1C), compared to control IVDs (0.67 ± 0.039 ng/ml). Degenerating, painful IVDs released detectable amounts of IL-1β, but not all healthy, pain-free IVDs released IL-1β above the detection limit (0.48 pg/ml) of the assay (data not shown). Therefore, the difference between the two groups was not determined.


Painful, degenerating intervertebral discs up-regulate neurite sprouting and CGRP through nociceptive factors.

Krock E, Rosenzweig DH, Chabot-Doré AJ, Jarzem P, Weber MH, Ouellet JA, Stone LS, Haglund L - J. Cell. Mol. Med. (2014)

Tumour necrosis factor-α (TNF-α; A), nerve growth factor (NGF; B) and brain derived neurotrophic factor (BDNF; C) mean concentrations in media from healthy pain-free or degenerating, painful intervertebral disc (IVDs). n = 8 in degenerate, painful group and n = 11 in healthy, pain-free group for TNF-α and NGF ±95% CI, unpaired t-test. n = 7 in degenerating, painful group and n = 9 in healthy, pain-free group for BDNF, ±95% CI, Mann–Whitney test. **P < 0.01, ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508160&req=5

fig01: Tumour necrosis factor-α (TNF-α; A), nerve growth factor (NGF; B) and brain derived neurotrophic factor (BDNF; C) mean concentrations in media from healthy pain-free or degenerating, painful intervertebral disc (IVDs). n = 8 in degenerate, painful group and n = 11 in healthy, pain-free group for TNF-α and NGF ±95% CI, unpaired t-test. n = 7 in degenerating, painful group and n = 9 in healthy, pain-free group for BDNF, ±95% CI, Mann–Whitney test. **P < 0.01, ***P < 0.001.
Mentions: As isolated IVD cells can release inflammatory and nuerotrophic factors [27,28] and histological analyses of degenerate tissue have confirmed this [8,29], we quantified the ability of degenerating IVDs to actively release these factors ex vivo into culture media. Intervertebral discs was cultured on a volume per weight. ELISA analysis revealed that degenerating, painful IVDs released a significantly greater amount of TNF-α (138.3 ± 24.7 pg/ml, P = 0.01, Fig.1A) compared to healthy, pain-free IVDs (69.2 ± 22.6 pg/ml). NGF released at a significantly greater amount by degenerating, painful IVDs (44.2 ± 6.5 pg/ml, P < 0.001, Fig.1B) compared to healthy, pain-free IVDs (12.5 ± 4.5 pg/ml). Brain derived neurotrophic factor was significantly higher in the media from degenerating, painful IVDs (1.54 ± 0.026 ng/ml, P = 0.004, Fig.1C), compared to control IVDs (0.67 ± 0.039 ng/ml). Degenerating, painful IVDs released detectable amounts of IL-1β, but not all healthy, pain-free IVDs released IL-1β above the detection limit (0.48 pg/ml) of the assay (data not shown). Therefore, the difference between the two groups was not determined.

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.

View Article: PubMed Central - PubMed

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