Effect of atorvastatin on angiogenesis in degenerated intervertebral disc in rat.

STUDY DESIGN: An experimental study to measure the depth of penetration of new vessels in degenerated intervertebral disc in rat. OBJECTIVE: To evaluate the effects of atorvastatin on angiogenesis in experimental disc degeneration in rat. SUMMARY OF BACKGROUND DATA: Back pain is strongly associated with degenerated intervertebral disc and management of this condition is still empirical. Decrease of nucleus nutrition due to loss of vascularity with aging may aggravate the process of disc degeneration. So, angiogenesis may be useful in the healing process of degenerated disc. In this study, we wanted to evaluate the effect of atorvastatin, whose stimulating effect on angiogenesis on other tissues was shown in several studies, on degenerated intervertebral disc in rat. METHODS: Atorvastatin was administered intraperitoneally for 6 weeks in doses of 1, 4, and 8 mg/kg in rats after experimental disc degeneration. The rats intervertebral disc sections were stained immunohistochemically for von Willebrand Factor to evaluate the depth of vessels penetration and degree of vascularity. RESULTS: In the nonoperated control group, the intervertebral discs were avascular. But experimental disc degeneration promoted angiogenesis. In this group, the mean of penetration was 49.25 µ (standard deviation = 19.905). Atorvastatin stimulated angiogenesis after experimental disc degeneration in the rats and the angiogenesis was more significant in the high and medium dose groups than operated control group. High-dose atorvastatin could not inhibit angiogenesis in experimental degenerated disc. There was no any significant difference in degree of vascularity among the groups. CONCLUSION: Atorvastatin stimulates angiogenesis in experimental disc degeneration in rats. But, it does not show a biphasic effect.

The effects of calcium channel antagonist nimodipine on end-plate vascularity of the degenerated intervertebral disc in rats.

The vascular channels at the end-plate of the intervertebral disc are very important in maintaining a healthy disc. With age, a reduction of the nutrition of the avascular nucleus pulposus is inevitable. On the other hand the calcium channel antagonist nimodipine has been shown to have a positive effect on blood flow in the region of the vertebral end-plate. To evaluate the effects of nimodipine on the end-plate vascularity in the degenerative discs, we have produced an experimental disc degeneration and evaluated the radiological and histopathological features of the end-plate of the degenerated discs. Adult rats were divided into 3 groups: control (n=5), operated degeneration (n=5), and nimodipine treatment (n=5). Using a posterior approach, a cut was made parallel to the end-plates in the posterior annulus fibrosus in 5 consecutive intervertebral discs between the 5th and 10th vertebral segments of the tails of adult Swiss Albino rats. At 8 weeks, 5 of these animals were treated with nimodipine. In each experimental group, 1 animal was examined using computed tomography (CT) to study the density of the cartilage end-plate of the disc. Then, the animals were sacrificed for subsequent histopathological evaluation. We found that the vascular channel counts and percentage areas from animals treated with nimodipine were higher than from both the non-operative control and operated degeneration groups, although these were not statistically different. Accordingly, the profile of the density histogram in the nimodipine-treated group showed a wide plateau, indicating an increase in the vascularity in this region. From our results, we suggest that nimodipine enhances vascularisation of the cartilage end-plate in the disc. It is possible that the increased proportion of vascular contacts at the end-plate has a beneficial effect in the nutrition of the disc. However, further experimental studies will be needed to determine the validity of this statement in animals or human beings.