Degenerative disorders of the intervertebral discs (IVDs) are generally characterized by enhanced matrix degradation, angiogenesis, innervation, and increased expression of catabolic cytokines. In this study, we investigated the effects of inflammatory cytokines, IL-1␤, and TNF-␣, on the expression of an angiogenic factor, vascular endothelial growth factor (VEGF), and neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), in human IVD degeneration. IL-1␤ and TNF-␣ stimulated the gene expression of VEGF, NGF, and BDNF in nucleus pulposus (NP) cells isolated from patient tissues. Immunohistochemical results demonstrated a positive correlation between IL-1␤ and VEGF/NGF/BDNF expression in human IVD tissues. RNA expression analysis of patient tissues also identified positive correlations between VEGF and platelet endothelial cell adhesion molecule-1 (PECAM-1) and between NGF/BDNF and protein gene product 9.5 (PGP9.5). Our findings suggest that IL-1␤ is generated during IVD degeneration, which stimulates the expression of VEGF, NGF, and BDNF, resulting in angiogenesis and innervation. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J. Orthop. Res. 29: 265-269, 2011 Keywords: interleukin-1␤; vascular endothelial growth factor (VEGF); angiogenesis; innervation; intervertebral disc (IVD) Degenerative changes in intervertebral discs (IVDs) include increased expression of catabolic cytokines, decreased synthesis of normal IVD matrix and enhanced matrix degradation, and disc cell senescence and apoptosis.1-5 IVD degeneration results in the loss of hydrophilic matrix molecules leading to spinal instability and is the main cause of disc-related diseases, such as disc herniation and spinal stenosis. Normal lumbar IVD is avascular and aneural except for the outer third of the annulus fibrosus (AF). However, previous studies have described the ingrowth of nerves into the AF and nucleus pulposus (NP) of degenerated IVD 6,7 and these nerves were usually accompanied by microvascular blood vessels.8 Though, the mechanisms underlying nerve ingrowth and neovascularization are largely unknown.Neurotrophins play a role in the survival, growth, differentiation, and function of neurons.9 The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been detected in human IVD degeneration and have been implicated in the promotion of nerve ingrowth and generation of discogenic pain. 8,10,11 A histologic study examining degenerative IVD tissues from rats demonstrated that the major population of disc-innervating dorsal root ganglion neurons was the NGF-dependent neurons.

BackgroundThe purpose of this study was to determine the reaction mechanism of corticosteroid by analyzing the expression patterns of neuropeptides (substance P (SP), calcitonin gene related peptide (CGRP)) and of cytokines (interleukin (IL)-1α, tumor growth factor (TGF)-β) after corticosteroid treatment in lateral epicondylitis. In addition, we also investigated whether corticosteroid influenced tenocyte viability.MethodsThe corticosteroid triamcinolone acetonide (TAA) was applied to cultured tenocytes of lateral epicondylitis, and the changes in the mRNA expressions of neuropeptides and cytokines and tenocyte viabilities were analyzed at seven time points. Quantitative real-time polymerase chain reaction and an MTT assay were used.ResultsThe expression of SP mRNA was maximally inhibited by TAA at 24 hours but recovered at 72 hours, and the expressions of CGRP mRNA and IL-1α mRNA were inhibited at 24 and 3 hours, respectively. The expression of TGF-β mRNA was not significant. Tenocyte viability was significantly reduced by TAA at 24 hours.ConclusionsWe postulate that the reaction mechanism predominantly responsible for symptomatic relief after a corticosteroid injection involves the inhibitions of neuropeptides and cytokines, such as, CGRP and IL-1α. However the tenocyte viability was compromised by a corticosteroid.