Increase of nerve growth factor levels in the human herniated intervertebral disc: can annular rupture trigger discogenic back pain?

Abstract

IntroductionNerve growth factor (NGF) has an important role in the generation of discogenic pain. We hypothesized that annular rupture is a trigger for discogenic pain through the action of NGF. In this study, the protein levels of NGF in discs from patients with disc herniation were examined and compared with those from discs of patients with other lumbar degenerative disc diseases.MethodsPatients (n = 55) with lumbar degenerative disc disease treated by surgery were included. Nucleus pulposus tissue (or herniated disc tissue) was surgically removed and homogenized; protein levels were quantified using an enzyme-linked immunosorbent assay (ELISA) for NGF. Levels of NGF in the discs were compared between 1) patients with herniated discs (herniated group) and those with other lumbar degenerative disc diseases (non-herniated group), and 2) low-grade and high-grade degenerated discs. Patient’s symptoms were assessed using a visual analog scale (VAS) and the Oswestry disability index (ODI); the influence of NGF levels on pre- and post-operative symptoms was examined.ResultsMean levels of NGF in discs of patients were significantly higher in herniated discs (83.4 pg/mg total protein) than those in non-herniated discs (68.4 pg/mg).No significant differences in levels of NGF were found between low-grade and high-grade degenerated discs. Multivariate analysis, adjusted for age and sex, also showed significant correlation between the presence of disc herniation and NGF levels, though no significant correlation was found between disc degeneration and NGF levels. In both herniated and non-herniated groups, pre-operative symptoms were not related to NGF levels. In the herniated group, post-operative lower extremity pain and low back pain (LBP) in motion were greater in patients with low levels of NGF; no significant differences were found in the non-herniated group.ConclusionsThis study reports that NGF increased in herniated discs, and may play an important role in the generation of discogenic pain. Analysis of patient symptoms revealed that pre-operative NGF levels were related to post-operative residual lower extremity pain and LBP in motion. The results suggest that NGF in the disc is related to pain generation, however, the impact of NGF on generation of LBP varies in individual patients.Electronic supplementary materialThe online version of this article (doi:10.1186/ar4674) contains supplementary material, which is available to authorized users.

The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

“…Studies have showed various types of activated immunocytes and inflammatory factors were recruited in NP-nerve root area [62,63]. The immunocytes were identified including macrophages, T cells, B cells, NK cells and mast cells, and the inflammatory factors were detected such as phospholipase A2 [64], leukotrienes [65], fibroblast growth factor [66], the IL family [66], tumor necrosis factors [67], matrix metalloproteinases [68], nitric oxide [69], substance P [70], monocyte chemoattractant protein-1 [71], vascular endothelial growth factor [72] and nerve growth factor [73]. These factors constitute a complicated region contributing to the immune stress of the nerve root.…”

The effect of serotonin–noradrenaline reuptake inhibitor duloxetine on the intervertebral disk-related radiculopathy in rats

“…Nerve growth factor (NGF), one of the neurotrophic factors, is involved in pain related to IVD degeneration [46] and herniation [2]. It has been reported that herniated NP also increases production of brain-derived neurotrophic factor (BDNF) in pain-processing neurons [34], which can correlate with pain sensitivity in the rat model [15,16,41,45].…”

Low Back Pain in Patients with Lumbar Spinal Stenosis-Hemodynamic and electrophysiological study of the lumbar multifidus muscles

“…Aoki et al demonstrated using a new detailed VAS system that nonspecific LBP in elderly patients was present in motion, besides during standing and sitting 18) . Recently, LBP in motion was related to an increase in the nerve growth factor level in the intervertebral disc, which led to discogenic LBP 19) . Some authors reported that walking-induced LBP 20) and the LBP with the neuropathic component 21) had better response to pregabalin known as a therapeutic agent for neuropathic pain.…”