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

Yasuchika Aoki14*, Arata Nakajima1, Seiji Ohtori2, Hiroshi Takahashi1, Fusako Watanabe1, Masato Sonobe1, Fumiaki Terajima1, Masahiko Saito1, Kazuhisa Takahashi2, Tomoaki Toyone3, Atsuya Watanabe4, Takayuki Nakajima4, Makoto Takazawa4 and Koichi Nakagawa1

Author Affiliations

1 Department of Orthopaedic Surgery, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura, Chiba 285-8741, Japan

2 Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba 260-8677, Japan

3 Department of Orthopaedic Surgery, Teikyo University Chiba Medical Center, 3426-3 Anesaki, Ichihara-city, Chiba 299-0111, Japan

4 Department of Orthopaedic Surgery, Eastern Chiba Medical Center, 3-6-2 Okayamadai, Togane, Chiba 283-8686, Japan

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Arthritis Research & Therapy 2014, 16:R159  doi:10.1186/ar4674

Published: 28 July 2014



Nerve 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.


Patients (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.


Mean 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.


This 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.