Possible pathogenesis of painful intervertebral disc degeneration.
METHODS
We collected the specimens of lumbar intervertebral disc (i.e., the symptomatic degenerative disc) from patients with discogenic low back pain to study the histopathologic features and growth factor expressions.


OBJECTIVE
To study the pathogenesis of disc degeneration, meanwhile discriminating between common disc degeneration (aging disc) (i.e., black asymptomatic disc, not clinically relevant) and painful disc degeneration (i.e., symptomatic disc, clinically relevant).


BACKGROUND
The pathogenesis of intervertebral disc degeneration is poorly understood, mainly because of the difficulty to establish the experimental model with good reproducibility. Recently, the popularity of spinal fusion leads to more opportunities to obtain disc specimens, which could be applied to explore the pathogenesis of disc degeneration with modern biologic techniques.


METHODS
There were 21 specimens of lumbar intervertebral discs from 15 patients with discogenic low back pain during posterior lumbar interbody fusion, 16 aging discs from patients without low back pain, and 10 normal discs as control collected for the study of their histopathologic features, as well as the expressions of basic fibroblast growth factor (bFGF) and its receptor (Flg), transforming growth factor-beta1 (TGF-beta1) and its receptor (TGF-betaRI) by immunohistochemistry. The distribution of macrophages and mast cells was also noted. Proliferating cell nuclear antigen was assessed to evaluate proliferating activities of disc cells.


RESULTS
The distinct histologic characteristic of the disc from the patient with discogenic low back pain was the ingrowth of vascularized granulation tissue along torn fissures, extending from the external layer of the anulus fibrosus into the nucleus pulposus. The immunohistochemical staining showed that there were strong expressions of bFGF and TGF-beta1 and their receptors, as well as a strong expression of proliferating cell nuclear antigen in the zones of granulation tissue in the painful discs. However, there were only weak expressions in the nongranulation tissue zones in the painful discs and aging discs, and no expression in the control discs. In addition, abundant macrophages and mast cells were found in the granulation tissue zones of painful discs but absent in the nongranulation tissue zones of painful discs or aging discs and the normal control discs.


CONCLUSIONS
The findings indicated that degeneration of the painful disc might originate from the injury and subsequent repair of anulus fibrosus. Growth factors, such as bFGF and TGF-beta1, macrophages and mast cells might play a key role in the repair of the injured anulus fibrosus and subsequent disc degeneration.
Peng
Baogan
B
Department of Orthopaedics, 304th hospital, Beijing, China. pengbaogan@163.com
Hao
Jianhua
J
Hou
Shuxun
S
Wu
Wenwen
W
Jiang
Duyin
D
Fu
Xiaobing
X
Yang
Yi
Y
D000328:Adult; D000368:Aged; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D000091344:Filaggrin Proteins; D006097:Granulation Tissue / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology*; D007405:Intervertebral Disc Displacement / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D017116:Low Back Pain / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta; D013123:Spinal Fusion; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D018809:Proliferating Cell Nuclear Antigen; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D051496:Receptor, Fibroblast Growth Factor, Type 1