Loading…
Degenerating and Painful Human Intervertebral Discs Release Pronociceptive Factors and Increase Neurite Sprouting and CGRP via Nerve Growth Factor
Introduction Increasing evidence suggests that healthy and painless intervertebral discs (IVDs) are largely aneural and that degenerating and painful IVDs often are innervated.1 Many inflammatory factors are unregulated in disc degeneration, such as interleukin (IL)-1β, IL-6, and tumor necrosis fact...
Saved in:
| Published in: | Global Spine Journal 2014-05, Vol.4 (1_suppl), p.s-0034-1376539-s-0034-1376539 |
|---|---|
| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
| Online Access: | Request full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Introduction
Increasing evidence suggests that healthy and painless intervertebral discs (IVDs) are largely aneural and that degenerating and painful IVDs often are innervated.1 Many inflammatory factors are unregulated in disc degeneration, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), and are believed to play important roles in degeneration and pain.2,3 Increased levels of neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), have also been associated with disc degeneration and could potentiate disc innervation.4 Inflammatory factors and neurotrophins can also have nociceptive roles that promote the development of chronic pain. While increased levels of inflammatory and nociceptive factors have been found by histological analysis in degenerating discs, in disc cell cultures, and in animal models,3 the ability of degenerating intervertebral discs from chronic low back pain patients to release increased levels of nociceptive factors compared with healthy discs from pain free donors is unknown. An understanding of the ability of degenerating discs to release nociceptive factors that may sensitize neurons and the mechanisms involved will provide evidence to develop effective pain management strategies.
Materials and Methods
Degenerating, painful IVDs were collected from patients undergoing surgery for low back pain and healthy, painless IVDs were collected from human organ donors through Transplant Quebec. IVDs were cultured ex vivo for 48 hours and the conditioned media was collected. Protein arrays were used to assess relative quantities of 23 cytokines and chemokines and enzyme-linked immunosorbent assay (ELISA) kits were used to quantify TNF-α, NGF, and BDNF in the conditioned media. PC12 cells, a neuronal-like cell line, were exposed to the conditioned or NGF supplemented media and neurite sprouting was analyzed. Mouse sensory neurons were isolated from dorsal root ganglia and treated with conditioned media. Neuronal expression of CGRP, a peptide involved in pain modulation, was compared with the total number of neurons that were stained with PGP 9.5, a general neuronal marker and the percentage of CGRP immunoreactive neurons was determined. To determine the role of NGF in neurite sprouting and CGRP regulation NGF supplemented or degenerating IVD conditioned media was incubated with an anti-NGF antibody. Cytokine array data were analyzed by unpaired t-tests and neurite sprouting and CGRP |
|---|---|
| ISSN: | 2192-5682 2192-5690 |
| DOI: | 10.1055/s-0034-1376539 |