intradiscal injection
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JOR Spine ◽  
2021 ◽  
Author(s):  
Fu Zhang ◽  
Songjuan Wang ◽  
Baoliang Li ◽  
Wei Tian ◽  
Zhiyu Zhou ◽  
...  

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Takao Sudo ◽  
Koji Akeda ◽  
Koki Kawaguchi ◽  
Takahiro Hasegawa ◽  
Junichi Yamada ◽  
...  

Abstract Background Establishing an optimal animal model for intervertebral disc (IVD) degeneration is essential for developing new IVD therapies. The intra-articular injection of monosodium iodoacetate (MIA), which is commonly used in animal models of osteoarthritis, induces cartilage degeneration and progressive arthritis in a dose- and time-dependent manner. The purpose of this study was to determine the effect of MIA injections into rabbit IVDs on the progression of IVD degeneration evaluated by radiographic, micro-computerized tomography (micro-CT), magnetic resonance imaging (MRI), and histological analyses. Methods In total, 24 New Zealand White (NZW) rabbits were used in this study. Under general anesthesia, lumbar discs from L1–L2 to L4–L5 had a posterolateral percutaneous injection of MIA in contrast agent (CA) (L1–L2: CA only; L2–L3: MIA 0.01 mg; L3–L4: 0.1 mg; L4–L5: 1.0 mg; L5–L6: non-injection (NI) control). Disc height was radiographically monitored biweekly until 12 weeks after injection. Six rabbits were sacrificed at 2, 4, 8, and 12 weeks post-injection and processed for micro-CT, MRI (T2-mapping), and histological analyses. Three-dimensional (3D) disc height in five anatomical zones was evaluated by 3D reconstruction of micro-CT data. Results Disc height of MIA-injected discs (L2–L3 to L4–L5) gradually decreased time-dependently (P < 0.0001). The disc height of MIA 0.01 mg-injected discs was significantly higher than those of MIA 0.1 and 1.0 mg-injected discs (P < 0.01, respectively). 3D micro-CT analysis showed the dose- and time-dependent decrease of 3D disc height of MIA-injected discs predominantly in the posterior annulus fibrosus (AF) zone. MRI T2 values of MIA 0.1 and 1.0 mg-injected discs were significantly decreased compared to those of CA and/or NI controls (P < 0.05). Histological analyses showed progressive time- and dose-degenerative changes in the discs injected with MIA (P < 0.01). MIA induced cell death in the rabbit nucleus pulposus with a high percentage, while the percentage of cell clones was low. Conclusions The results of this study showed, for the first time, that the intradiscal injection of MIA induced degenerative changes of rabbit IVDs in a time- and dose-dependent manner. This study suggests that MIA injection into rabbit IVDs could be used as an animal model of IVD degeneration for developing future treatments.


Author(s):  
Hua Jiang ◽  
Abu Moro ◽  
Jiaqi Wang ◽  
Dihua Meng ◽  
Xinli Zhan ◽  
...  

AbstractRecent studies have demonstrated the pivotal role played by microRNAs (miRNAs) in the etiopathogenesis of intervertebral disc degeneration (IDD). The study of miRNA intervention in IDD models may promote the advancement of miRNA-based therapeutic strategies. The aim of the current study was to investigate whether intradiscal delivery of miRNA can attenuate IDD development. Our results showed that miR-338-3p expression was significantly increased in the nucleus pulposus (NP) of patients with IDD. Moreover, there was a statistically significant positive correlation between the expression level of miR-338-3p and the severity of IDD. Our functional studies showed that miR-338-3p significantly influenced the expression of extracellular matrix synthesis genes, as well as the proliferation and apoptosis of NP cells. Mechanistically, miR-338-3p aggravated IDD progression by directly targeting SIRT6, a negative regulator of the MAPK/ERK pathway. Intradiscal injection of antagomir-338-3p significantly decelerated IDD development in mouse models. Our study is the first to identify miR-338-3p as a mediator of IDD and thus may be a promising target for rescuing IDD.


2021 ◽  
Vol 22 (17) ◽  
pp. 9609
Author(s):  
Carla Cunha ◽  
Catarina Leite Pereira ◽  
Joana R. Ferreira ◽  
Cláudia Ribeiro-Machado ◽  
Sibylle Grad ◽  
...  

Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5) that combines a hyaluronan-based thermoreversible hydrogel (HAP) and the chemokine stromal cell derived factor-1 (SDF-1). HAPSDF5 was injected into the IVD and was combined with an intravenous injection of mesenchymal stem/stromal cells (MSCs) in a pre-clinical in vivo IVD lesion model. The local and systemic effects were evaluated two weeks after treatment. The hydrogel by itself (HAP) did not elicit any adverse effect, showing potential to be administrated by intradiscal injection. HAPSDF5 induced higher cell numbers, but no evidence of IVD regeneration was observed. MSCs systemic injection seemed to exert a role in IVD regeneration to some extent through a paracrine effect, but no synergies were observed when HAPSDF5 was combined with MSCs. Overall, this study shows that although the injection of chemoattractant hydrogels and MSC recruitment are feasible approaches for IVD, IVD regeneration using this strategy needs to be further explored before successful clinical translation.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1178
Author(s):  
Tijn Wiersema ◽  
Anna R. Tellegen ◽  
Martijn Beukers ◽  
Marijn van Stralen ◽  
Erik Wouters ◽  
...  

Back pain affects millions globally and in 40% of the cases is attributed to intervertebral disc degeneration. Oral analgesics are associated with adverse systemic side-effects and insufficient pain relief. Local drug delivery mitigates systemic effects and accomplishes higher local dosing. Clinical efficacy of intradiscally injected celecoxib (CXB)-loaded polyesteramide microspheres (PEAMs) was studied in a randomized prospective double-blinded placebo controlled veterinary study. Client-owned dog patients suffering from back pain were treated with CXB-loaded (n = 20) or unloaded PEAMs (“placebo”) (n = 10) and evaluated by clinical examination, gait analysis, owners’ questionnaires, and MRI at 6 and 12 weeks follow-up. At 6 and 12 weeks, CXB-treated dogs experienced significantly less pain interference with their daily life activities compared to placebo. The risk ratio for treatment success was 1.90 (95% C.I. 1.24–2.91, p = 0.023) at week 6 and 1.95 (95% C.I. 1.10–3.45, p = 0.036) at week 12. The beneficial effects of CXB-PEAMs were more pronounced for the subpopulation of male dogs and those with no Modic changes in MRI at inclusion in the study; disc protrusion did not affect the outcome. It remains to be determined whether intradiscal injection of CXB-PEAMs, in addition to analgesic properties, has the ability to halt the degenerative process in the long term or restore the disc.


2021 ◽  
Vol 4 (5) ◽  
pp. 46
Author(s):  
Osvaldo Alberto Pepa

MODIC changes of signal in lumbar MRI offered a new vision of the spine degenerations process. Several theories try to explain this phenomenom. After a critical apraisal and based on our own experience, we propose ozone intradiscal injection as an effective and safe treatment for disc degeneration disease.


2021 ◽  
Vol 4 (5) ◽  
pp. 24
Author(s):  
Gabriel Calle ◽  
Lucio Huayhua ◽  
Alexis Martinez

The results obtained from a group of patients suffering from discoradicular conflict syndrome treated with paravertebral oxygen-ozone injections were analyzed. From a total number of 8500 patients treated with ozone during the period 2002/2015, 880 patients underwent intradiscal injection and 7620 patients were treated with paravertebral ozone injections. This paper analyses a subgroup of 1850 patients (24.28% of the patients who were treated with paravertebral injections), including those patients who underwent the total 10-session treatment, complied with a 5-year follow-up and with the sample homogeneity parameters following a predictability therapeutic effectiveness (PET) index devised for such purpose (PET index O3) by us in 2009. The outcomes were assessed based on the VAS score and modified Mac Nab criteria. Definite results determined positive post-treatment outcomes considered excellent and good in 81% of the cases. Such effectiveness percentage resulted lower than the one achieved with the intradiscal injection technique (89%), and higher than the percentage seen in papers on the selective nerve root block technique.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaodong Huang ◽  
Wei He ◽  
Weiheng Wang ◽  
Quanchun Fan ◽  
Xiaojian Ye ◽  
...  

To test the pharmacokinetics and toxicology of whole organs and tissues after intradiscal injection of simvastatin in rabbits. To provide the information needed to support human clinical trials. Twelve male and twelve female rabbits were randomly divided into four groups: control group (0 mg/ml), low dose group (0.1 mg/ml), medium dose group (1 mg/ml) and high dose group (10 mg/ml). Simvastatin at different concentrations of 10 μl was injected into L3/4, L4/5 and L5/6 intervertebral discs in each group. Poly (ethylene glycol) -poly (lactic-co-glycolic acid) -poly (ethylene glycol) (PEG-PLGA-PEG) polymer as the drug carrier. The pharmacokinetics of blood samples were measured by LC-MS/MS. Cerebrospinal fluid was obtained and the drug concentration was measured. Blood routine, blood biochemistry and urine of all animals were analyzed and evaluated. The heart, kidney, liver and spleen of each animal were observed and weighed. The intervertebral disc tissues were stained with hematoxylin and hematoxylin (H&amp;E), and then qualitatively analyzed by optical microscopy. 28 days after intradiscal injection of simvastatin, 28 days after simvastatin intradiscal injection, there was no significant difference between the weight, food residue, blood routine, blood biochemistry, urine routine results and the weight of each organ in the four groups (p &gt; 0.05). The serum concentration of simvastatin is lower than the lowest measurable concentration. The histological score of the intervertebral disc in the high-dose group was significantly higher than that in the other three groups at 28 days (p &lt; 0.05). Three doses of simvastatin were injected into male and female animals respectively, showing no toxic effects. Microscopic histological evaluation of the intervertebral disc showed that the high dose group (10 mg/ml) had damage to the intervertebral disc tissue.


2021 ◽  
Vol 15 ◽  
Author(s):  
Xiaodong Huang ◽  
Changkun Zheng ◽  
Weiheng Wang ◽  
Xiaojian Ye ◽  
Chia-Ying Lin ◽  
...  

To study the effect of intradiscal injection of simvastatin on discogenic pain in rats and its possible mechanism, 30 adult female rats were used in this experiment. Twenty rats were randomly divided into sham operation group (Control group), intervertebral disk degeneration group (DDD group), intervertebral disk degeneration + hydrogel group (DDD + GEL group), and intervertebral disk degeneration + simvastatin group (DDD + SIM group). The mechanical pain threshold and cold sensation in rats were measured. The contents of NF-kappa B1, RelA, GAP43, SP, CGRP, TRPM 8, IL-1β, and TNF-α in the intervertebral disk (IVD), the corresponding contents of dorsal root ganglion (DRG) and plantar skin GAP43 and TRPM 8 were quantitatively detected by PCR. The corresponding IVDs were stained to detect their degeneration. There was no significant difference in the mechanical pain threshold between the groups at each time point. From the first day to the 8th week after surgery, the cold-sensing response of the DDD group was significantly higher than that of the Control group (P &lt; 0.05). At 7 and 8 weeks postoperatively, the cold-sensing response of the DDD + SIM group was significantly lower than that of the DDD + GEL group (P &lt; 0.05). The levels of NF-κB1, RelA, GAP43, SP, CGRP, TRPM8, IL-1β, and TNF-α in the IVD of DDD + SIM group were significantly lower than those in DDD group (P &lt; 0.05). The content of GAP43 and TRPM8 in rat plantar skin decreased significantly and TRPM8 in DRG decreased significantly (P &lt; 0.05).


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