Since the concept of DLBP was first proposed by crock in 1970 [5]. People have further understanding of intervertebral disc disease, and think that DLBP is to exclude disc herniation and joint surface pain in symptoms [15], and to exclude low back pain caused by intervertebral disc degeneration (intervertebral disc structure disorder) in imaging [24]. Although the study of intervertebral disc has lasted for many years, there is still a lack of diagnostic criteria for DLBP. Discography is an important method to diagnose DLBP. Discography was first proposed by Lindbloom in 1948. It is an invasive diagnostic technique by injecting contrast agent into intervertebral disc to observe the shape of intervertebral disc [4], which has been controversial since the beginning of Invention [3, 16, 36]. Although there are controversies, discography is widely used in clinical practice. It has the advantages that other examination items can't replace: typical pain duplication, fine and intuitive display of intervertebral disc injury. A systematic review showed that: according to the International Association for pain research (IASP) standard, discography may be a useful tool for evaluating chronic discogenic pain [16], and some articles also confirmed that CT examination immediately after discography is the "gold standard" for the diagnosis of DLBP [28]. Simvastatin used in this experiment can be injected into the suspected diseased intervertebral disc together with contrast agent or blocking agent during discography and intervertebral disc block. On the one hand, it can play an auxiliary role in diagnosis, on the other hand, it can assist in treatment.
Simvastatin is a widely studied and well tolerated drug, which is known to upregulate the expression of BMP-2A [37]. Simvastatin, an inhibitor of HMG CoA reductase, is a traditional cheap lipid-lowering drug. It interferes with liver cholesterol synthesis by inhibiting HMG CoA reductase, an enzyme involved in cholesterol production through the mevalonate pathway [8]; therefore, statins can reduce serum cholesterol levels and significantly reduce mortality associated with coronary heart disease [12, 17]. Zhang et al. have shown that simvastatin can increase the expression of BMP-2 mRNA in rats [37]. At the same time, it can also up regulate the gene expression of glycosaminoglycan and type II collagen and the content of proteoglycan, which indicates that simvastatin can enhance the function of intervertebral disc cell synthesis. This provides a theoretical basis for choosing simvastatin in the treatment of DLBP. The results of body weight change, food residue and routine hematuria showed that simvastatin injection into intervertebral disc had no adverse effect on animals.
The clinical manifestation of DLBP is the decrease of intervertebral space height and the decrease of water signal on T2 image of MRI. Although MRI has been widely considered as a sensitive index in the diagnosis of DLBP, the traditional MRI technology has not fully evaluated the early degeneration of intervertebral disc [14]. This study is one of the first studies to evaluate early intervertebral disc degeneration, such as changes in extracellular matrix, especially changes in water signal, using the newly developed specialized MRI technology (T2 anchor technique) [7, 34]. The best way to repair the intervertebral disc is to protect the uninjured disc tissue as much as possible, and increase the expression of water containing substances (type 2 collagen and glycosaminoglycan) in the intervertebral disc to maintain its seismic resistance. At present, most of the latest biological therapy methods are based on the above theory, such as autologous cell transplantation, injection of growth factor and gene therapy. This study aims to verify a promising treatment method, which is easier for clinical transformation. Our results show that a single dose of simvastatin can reduce the loss of disc height, and DDD + high group can reduce the loss of disc height. At the same time, the three concentrations of simvastatin injected into the intervertebral disc can increase the T2 image water signal intensity of intervertebral disc MRI, and the high-dose simvastatin treatment group can increase the T2 image water signal intensity of intervertebral disc MRI. Simvastatin can increase the water content of the intervertebral disc. These results suggest that intradiscal injection of simvastatin can reduce disc degeneration, which is consistent with previous studies that local injection of simvastatin in rats has delayed or regenerative degenerative discs [39]. At the same time, we also found that simvastatin has dose effect in the treatment of intervertebral disc degeneration.
In this study, we used a simple X-ray photography technique designed by Lü et al. To measure the intervertebral disc height: DHI [13]. In order to measure more accurately, we try the following aspects. First, we try to keep the rabbits in the same anesthesia state and maintain consistent muscle relaxation to minimize the difference in disc height. Second, recheck and adjust the rabbit's position before shooting until the projection of spinous process of rabbit's spine is located in the middle line of cone in the AP film; the projection of two transverse processes of spine overlaps in lateral film, indicating that the true anteroposterior and lateral films have been obtained (Fig. 3a, b). Third, keep the animal spine in a fixed position and aim at the X-ray beam to reduce the error caused by spinal rotation and beam divergence. In addition, measurements were repeated to minimize any inter subject variability in% DHI after disc puncture.
However, there are some shortcomings in this experiment, including the following points. First of all, acupuncture injection was used for intradiscal administration, and acupuncture itself destroyed the structural integrity of the intervertebral disc, resulting in intervertebral disc degeneration, which was directly related to the diameter of puncture needle. Although the needle with smaller diameter was used for drug administration in this experiment, and parallel control was conducted, the influence of acupuncture itself on intervertebral disc degeneration still could not be ruled out. At present, there is no ideal way of administration, which needs further study. Secondly, the longest experimental observation time of this study is only 6 months. We only observed the short-term and medium-term efficacy of simvastatin injection into degenerative intervertebral disc. Therefore, in future experiments, we will extend the observation time to determine whether the drug has a long-term therapeutic effect on intervertebral disc. Thirdly, the treatment of degenerative intervertebral disc was not randomized, and the selection of treatment segments was not randomized. Then the MRI examination to judge the degree of intervertebral disc degeneration in the experiment is to get the result by comparing the treated intervertebral disc with adjacent normal intervertebral disc, rather than comparing with the MRI before the treatment of the same intervertebral disc, which is easy to produce systematic error. Finally, the subjects of this study are New Zealand rabbits, which are reptiles, which are quite different from human beings. Therefore, in the following experiments, we will choose standing animals that are closer to human beings, such as monkeys, for preclinical trials. Due to the practical operation problems of ethics, the human body test has not been studied in this experiment, so the human body test needs to be further studied.