Inhibiting Vascular Endothelial Growth Factor in Injured Intervertebral Discs Attenuates Pain-Related Neuropeptide Expression in Dorsal Root Ganglia in Rats

STUDY DESIGN: An experimental animal study. PURPOSE: To evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin gene-related peptide (CGRP) in the dorsal ganglia in a rat model. OVERVIEW OF LITERATURE: Increased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury. METHODS: Through abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti-VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 µg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 µL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1–L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP. RESULTS: Compared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (p<0.05; 40.6% and 58.1% on postoperative day 1, 44.3% and 55.4% on day 7, and 42.4% and 59.3% on day 14). The percentage was higher in the control group compared with that of the sham group (p<0.05; sham group, 34.1%, 40.7%, and 33.7% on postoperative days 1, 7, and 14, respectively). CONCLUSIONS: Decreasing CGRP-positive cells using anti-VEGF therapy provides fundamental evidence for a possible therapeutic role of anti-VEGF in patients with discogenic lower back pain.

DCE-MRI assessment of adjacent vertebral blood perfusion of degenerated lumbar discs / 实用放射学杂志

Objective To analyze the correlation of intervertebral disc degeneration with the blood perfusion of its adjacent border of vertebral body by dynamic contrast‐enhanced MRI (DCE‐MRI) .Methods 3 .0T DCE‐MRI examinations were performed in 15 patients (50 discs) .Intervertebral discs from L1 to L5 were classified to normal group(17 discs) and degeneration group(33 discs) based on the Pfirrmann grading system .The DCE‐MRI pharmaeokinetic parameters of the region of interest(ROI):volume transfer constant (Ktrans ) ,blood volume(BV) and blood flow (BF) were obtained .Independent sample t test was used to compare normal group and de‐generation group .Results In normal group (n=17) ,the mean Ktrans ,BV and BF were (0 .036 2 ± 0 .011 2)min-1 ,(4 .81 ± 1 .17) mL/100 mL ,(5 .68 ± 1 .55) mL · min-1 · 100 mL -1 for the superior border of vertebral body ,and (0 .042 ± 0 .012 9)min-1 ,(5 .03 ± 0 .797) mL/100 mL ,(6 .02 ± 1 .28) mL · min-1 · 100 mL -1 for the inferior border of vertebral body .In degeneration group (n=33) ,the mean Ktrans ,BVand BF were (0 .030 4 ± 0 .011 2)min-1 ,(4 .22 ± 1 .03) mL/100 mL ,(4 .73 ± 1 .38) mL · min-1 · 100 mL-1 for the superior border of vertebral body ,and (0 .033 8 ± 0 .012 5) min-1 ,(4 .07 ± 0 .940) mL/100 mL ,(4 .72 ± 1 .43) mL · min-1 · 100 mL -1 for the inferior border of vertebral body .By statistical analysis :(1)There were no significant differences between superior border and inferior border of vertebral body in Ktrans ,BV and BF in normal group(t= -0 .98 ,-0 .479 ,0 .533 respectively ,P>0 .05 ) .(2)There were no significant differences between superior border and inferior border of vertebral body in K trans ,BV and BF in degeneration group(t= -0 .906 ,0 .497 ,0 .013 respectively ,P>0 .05) .(3)There were significant differences between normal group and degeneration group in Ktrans ,BV and BF(t= -2 .26 ,-3 .01 ,-2 .99 respectively ,P<0 .05) .Conclusion The bone marrow per‐fusion in degeneration group is decreased when compared to normal group with dynamic contrast‐enhanced MRI .Intervertebral disc degeneration correlates with the loss of its blood supply .

Expression of matrix aggrecanase 2 and a tissue inhibitor of metalloproteinases in degenerated intervertebral discs / 中华物理医学与康复杂志

Objective To observe the expression of aggrecanase 2 and a tissue inhibitor of metalloproteinase 3 (TIMP-3) in degenerate human lumbar intervertebral discs and their role in degeneration of the nucleus pulposus.Methods Pfirrmann classification was used to class degenerate intervertebral discs observed through MRI.They were divided into three groups:a control group (Pfirrmann grade Ⅰ-Ⅱ),a degeneration group (Pfirrmann grade Ⅲ-Ⅳ),and a severe degeneration group (Pfirrmann grade Ⅴ).A total of 45 cases accepted lumbar spine surgery for removing nucleus pulposus specimens.Each group contained 15 cases.After formalin-fixation and paraffin embedding,immunohistochemistry was used to detect aggrecanase 2 and TIMP-3 expression in the nucleus pulposus cells.Results The percentages of cells positive for aggrecanase 2 were (13.58 ± 7.76) ％,(33.48 ± 13.95) ％ and (56.00 ± 18.39) ％ in the control,degeneration and severe degeneration groups respectively.These differences had statistical significance.The percentages of cells positive for TIMP-3 were (34.78 ± 13.80) ％,(46.77 ± 10.98) ％ and (50.65 ± 16.45) ％,and these differences were again statistically significant.The aggrecanase 2/TIMP-3 ratios were also significantly different.Conclusion As the degree of degeneration of the nucleus pulposus increased,the expression of aggrecanase 2 and TIMP-3 rose,which indicates that both changes were closely connected with the degeneration.Their ratio was correlated with the degree of degeneration of the nucleus pulposus.

Effect of amygdalin on end-plate chondrocytes apoptosis induced by IL-1βderived from rat intervertebral discs / 中国药理学通报

Aim To observe the anti-apoptotic effect of different concentrations of amygdalin on the endplate chondrocytes induced by IL-1 βderived from rat inter-vertebral discs and explore the possible mechanism fur-ther.Methods Chondrocytes were obtained from endplate of one-month SD rat intervertebral discs and cultured primary chondrocytes.After identifying,they were divided into normal group,induced group and A-mygdalin 1 0 -2 mol·L -1 ,1 0 -3 mol·L -1 ,1 0 -4 mol· L -1 ,1 0 -5 mol · L -1 administration group.Then the apoptosis was detected by flow cytometry (FCM).Re-al-Time PCR was adopted to detect the mRNA expres-sion of Bax and Bcl-2.The protein expression of Bax and Bcl-2 was detected by Western blot.Results The apoptosis of the endplate chondrocytes induced by IL-1 βderived from rat intervertebral discs could be inhib-ited by amygdalin with different concentrations.Amyg-dalin could reduce the apoptotic rate analysed by FCM,down-regulate the Bax mRNA expression of Bax and up-regulate the Bcl-2 mRNA assayed by RT-PCR;compared with the induced group the differences were statistically significant (P <0.05).Besides,observa-tion of the protein expression of Bax and Bcl-2 by Western blot found that amygdalin 1 0 -4 mol · L -1 could inhibit the effect of IL-1 β,which could increase the protein expression of Bax and reduce the protein expression of Bcl-2.Conclusion Amygdalin has an effect on anti-apoptosis of the end-plate chondrocytes induced by IL-1 βderived from rat intervertebral discs and improve the degeneration of intervertebral discs.

Effects of Jinzhuyalong Ershiwuwei coral capsule on PLA2 in degenarated cervical intervertebral discs / 国际中医中药杂志

Objective To study the anti-inflammation mechanism of Jinzhuyalong Ershiwuwei coral capsule on cervical spondylosis by investigating Jinzhuyalong Ershiwuwei coral capsule on PLA2 in degenerated cervical intervertebral discs.Methods 60SD rats (SPF) were divided into a control group (15),a medicine model control group (15),a medicine modle 1 group (15),and a medicine model 2 group (15) by random lottery; Medicine model 1,2 groups were given Jinzhuyalong Ershiwuwei coral capsule powder 0.33 × 5 g/kg 0.66×5 g/kg,and added 1 ml distilled water dilution lavage,l/d,90 d,The unbalance of power cervical spondylosis animal models were chosen and C4～5 neck intervertebral discs were taken after 90 days.Millipore colorimetry methods were used to measure PLA2 activity in C4～5 cervical intervertebral discs.Results The PLA2 activity of the cervical intervertebral disc (12.37 ± 4.21) IU/mg · min-1 in the model group was significantly higher than the control group(2.56± 1.19)IU/mg· min-1 (P＜0.05).The cervical intervertebral disc PLA2 activity of medicine model group 1 (8.56± 2.13)IU/mg · min-1 and medicine model group 2 (5.58 ±2.39)IU/mg· min-1 was lower than the model control group(12.37±4.21)IU/mg· min-1,with significant differences (both P＜0.01).Conclusion Jinzhuyalong Ershiwuwei coral capsule could down regulate PLA2 activity in degenerated cervical intervertebral discs,and also decrease the production of some inflammaroty mediators.

Study of the proliferation ability of human degenerate nucleus pulposus and annular fibrosus cell in vitro / 国际生物医学工程杂志

ObjectiveTo explore the proliferation of human degenerate nucleus pulposus and annular fibrosus cell in vitro and compare the different biological behavior between the two kinds of cell after degeneration,and provide the new theoretical basis for the prevention and treatment of degenerative disc disease.MethodsThe samples of intervertebral disc tissue were collected from patients with lumbar disc herniation.The degree of degeneration was assessed by the pathological diagnosis and degenerate nucleus pulposus and annular fibrosus cell were cultured by enzymatic digestion and identified.In each case,the control groups of the nucleus pulposus cells and annulus fibrosus cells were cultured to the fifth generation.The inoculation density of cells was 1×105.The cell morphology of each generation was observed,while the proliferation of cells was detected by flow cytometry after 48h culture with the same conditions.ResultsThe degenerate nucleus pulposus cell and annular fibrosus cell were in good condition in vitro.The percentages of S phase cell and proliferation index (PI) were both on the rise with the subculture.The PI of nucleus pulposus cells reached the peak in the 3rd generation; The PI of annulus cells was the highest in the generation 5.The proliferation activity of degenerate nucleus pulposus cell in 2～4 generations was higher than the degenerate annular fibrosus cell within the same generations (P＜0.05).ConclusionDifferent proliferative characteristics of the degenerate nucleus pulposus and annular fibrosus cell confirmed that the disc degeneration is reversible.The response mechanisms to the degenerate micro-environment are completely different in vivo and affects the entire disc degeneration progress.

Ocronosis: descripción de dos casos familiares, reseña histórica y revisión de la literatura / Ochronosis: report of two familial cases, historical overview and review of the literature

La ocronosis es la manifestación de la alcaptonuria en el tejido conjuntivo, se origina por la alteración en el metabolismo del ácido homogentísico, producto de la mutación autosómica recesiva del gen HGO, en el brazo largo del cromosoma 3 (3q21-23). Es una patología infrecuente, que se caracteriza por la presencia de calcificaciones de los discos intervertebrales y depósito de ácido homogentísico en el tejido conjuntivo y los tendones. Se presentan dos casos compatibles con las características clínicas y radiológicas de ocronosis.

Ochronosis is the manifestation of alkaptonuria in the connective tissue. It is originated by the alteration in the metabolism of homogentisic acid, a product of autosomal recessive mutation of HGO, gene in the long arm of chromosome 3 (3q21-23). It is a rare disease, characterized by the presence of calcifications in the intervertebral discs and deposit of homogentisic acid in connective tissue and tendons. We present two compatibles cases with the clinical and radiological features of ochronosis.

Posterior Epidural Migration of Lumbar Ruptured Disc: Report of Two Cases

Disc fragment migration occurs in 35%-72% of lumbar disc herniations. Most of the herniated disc fragments migrate in the rostal, caudal and lateral directions. Posterior epidural disc fragment migration is a rare finding and posterior migration causing Cauda Equina syndrome is exceptionally rare. We report here on two cases of L4-5 disc fragment posterior epidural migration that caused Cauda Equina syndrome, and this was diagnosed by performing radiological examination, and we also include a review of the related literature.

Excision of lumbar intervertebral disc through the lateral approach

The lateral approach for the excision of lumbar intervertebral discs is presented and discussed, with special emphasis on the complications that may be encountered. Three cases showing the importance of myelography are presented. (Summary)

Radiological Analysis of Aging Changes of the Lumbar Intervertebral Disc / 체질인류학회지

The present study was carried out to clarify the anatomical changes of lumbar intervertebral discs by aging. Anterior height, posterior height, anteroposterior diameter of intervertebral discs were measured on 512 normal plain lateral radiographs of lumbosacral spine. And the indices of disc wedging and relative disc height were calculated. There was a cephalocaudal gradient of increase in the indices of disc wedging in all age groups. The indices of relative disc height were constant at all lumbar levels. These suggest that the lower disc is more wedge shaped and the height of discs changes in the constant ratio with that of vertebral body.

Clinical Study of Discitis in Adult / 대한정형외과학회잡지

A primary infection of the intervertebral disc in adult is an uncommon entity. Usually these patients are not actually ill and their symptoms have been present for some months. Pyogenic infection of the intervertebral disc in children was well documented by a number of authors,but this condition was less well recognized in the adult. We analysed 12 cases of discitis in adults which were treated at the Department of Orthopedic Surgery of Severance Hospital for 10 years from January 1975 to March 1984 by curettage and autogenous iliac bone graft through anterior approach. The results obtained from this study were as follows: 1. The average duration of symptoms before diagnosis was 9.6 months. 2. The lumbar spine was involved in 83% and next in thoracic spine. 3. The most prominent symptoms and signs are backache and local tenderness at the site of the lesion. 4. Ten patients had the preceding disease or definile past history of previous back surgery, myelogram, abscess, urinary tract infection, heavy lifting and back trauma. 5. The white cell count was of little value in the initial investigation, but the E.S.R. was raised in 67%. 6. Positive cultures from the intervertebral disc were obtained in 8 cases(67%). The causative organisms were 5 Staphylococcus, 2 E-coli, and 1 Pseudomonas aeruginosa. 7. The most common radiological finding on admission was narrowing of the intervertebral disc space, and the tomogram showed the most reliable finding for the preoperative diagnosis. 8. In the treatment, focal curettage or diskectomy and anterior fusion with autogenous iliac bone graft was done in all cases. Antibiotics were administrated for 4 to 10 weeks (average 5.5 weeks) after operation and the cast or brace was applied for immobilization. 9. Over-all clinical result were as follows; eight patients (67%) excellent, 3 patients good, 1 patient fair, and no recurrence.