scholarly journals The Effect and Possible Mechanism of Intradiscal Injection of Simvastatin in the Treatment of Discogenic Pain in Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiaodong Huang ◽  
Changkun Zheng ◽  
Weiheng Wang ◽  
Xiaojian Ye ◽  
Chia-Ying Lin ◽  
...  
Keyword(s):  
Pain Threshold ◽  
Intervertebral Disk ◽  
Control Group ◽  
Discogenic Pain ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration ◽  
Tnf Α ◽  
Intradiscal Injection ◽  
Mechanical Pain Threshold ◽  
Cold Sensing

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 < 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 < 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 < 0.05). The content of GAP43 and TRPM8 in rat plantar skin decreased significantly and TRPM8 in DRG decreased significantly (P < 0.05).

scholarly journals Pro-inflammatory, Pleiotropic, and Anti-inflammatory TNF-α, IL-6, and IL-10 in Experimental Porcine Intervertebral Disk Degeneration

2009 ◽  
Vol 46 (6) ◽  
pp. 1292-1300 ◽  
Author(s):  
S. Holm ◽  
Z. Mackiewicz ◽  
A. K. Holm ◽  
Y. T. Konttinen ◽  
V.-P. Kouri ◽  
...  
Keyword(s):  
Intervertebral Disk ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration ◽  
Tnf Α ◽  
Anti Inflammatory

scholarly journals Impact of NF-κB pathway on the intervertebral disc inflammation and degeneration induced by over‐mechanical stretching stress

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Hui Xu ◽  
Guobao Qi ◽  
Kunpeng Li ◽  
Keshi Yang ◽  
Dawei Luo ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Cell Model ◽  
Intervertebral Disk ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration ◽  
Tnf Α ◽  
Collagen Ii ◽  
Induced Apoptosis ◽  
Mechanical Stretching

Abstract Background Intervertebral disk degeneration (IVDD) contributes to low back pain. Increased cell apoptosis and inflammation, decreased extracellular matrix are associated with IVDD. Nuclear factor-kappa B (NF-κB) signaling pathway and inflammatory cytokines are implicated in the pathophysiology of IVDD. Methods In present study, we established a mechanical stretching stress-stimulated nucleus pulposus (NP) cell model. We knocked down NF-κB p65 by siRNA transfection to inhibit NF-κB and evaluated the effects of NF-κB inhibition on intervertebral disk degeneration. We applied the mechanical stretching stress on NP cells and inhibited NF-κB by siRNA, then evaluated the expression of inflammatory cytokines, matrix metalloproteinase (MMP), aggrecan, collagen II, and monitored viability and apoptosis of NP cells. Results Mechanical stretching stress induced the expression of TNF-α, IL-1β, NF-κB, MMP-3 and MMP-13, while inhibited the production of aggrecan and collagen II in NP cells. Mechanical stretching stress decreased the cell viability and induced apoptosis in NP cells. Inhibition of NF-κB by siRNA suppressed the production of TNF-α, IL-1β, NF-κB, MMP-3 and MMP-13, while upregulated the expression of aggrecan and collagen II in NP cells. Conclusions Inhibition of NF-κB by knocking down p65 suppressed over-mechanical stretching stress-induced cell apoptosis and promoted viability in NP cell. Inhibition of NF-κB suppressed inflammation and degeneration of NP cells in IVDD.

scholarly journals Melatonin Attenuates Intervertebral Disk Degeneration via Maintaining Cartilaginous Endplate Integrity in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiexing Wu ◽  
Yijie Liu ◽  
Jiacheng Du ◽  
Xiaoping Li ◽  
Jiayi Lin ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Intervertebral Disk ◽  
Control Group ◽  
Nuclear Factor ◽  
Matrix Degradation ◽  
Potential Mechanism ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration ◽  
Disk Height

ObjectiveThe aim of this study is to verify whether melatonin (Mel) could mitigate intervertebral disk degeneration (IVDD) in rats and to investigate the potential mechanism of it.MethodA rat acupuncture model of IVDD was established with intraperitoneal injection of Mel. The effect of Mel on IVDD was analyzed via radiologic and histological evaluations. The specific Mel receptors were investigated in both the nucleus pulposus (NP) and cartilaginous endplates (EPs). In vitro, EP cartilaginous cells (EPCs) were treated by different concentrations of Mel under lipopolysaccharide (LPS) and Luzindole conditions. In addition, LPS-induced inflammatory response and matrix degradation following nuclear factor kappa-B (NF-κB) pathway activation were investigated to confirm the potential mechanism of Mel on EPCs.ResultsThe percent disk height index (%DHI) and MRI signal decreased after initial puncture in the degeneration group compared with the control group, while Mel treatment protected disk height from decline and prevented the loss of water during the degeneration process. In the meantime, the histological staining of the Mel groups showed more integrity and well-ordered construction of the NP and EPs in both low and high concentration than that of the degeneration group. In addition, more deep-brown staining of type II collagen (Coll-II) was shown in the Mel groups compared with the degeneration group. Furthermore, in rat samples, immunohistochemical staining showed more positive cells of Mel receptors 1a and 1b in the EPs, instead of in the NP. Moreover, evident osteochondral lacuna formation was observed in rat EPs in the degeneration group; after Mel treatment, the osteochondral destruction alleviated accompanying fewer receptor activator for nuclear factor-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP)-stained positive cells expressed in the EPs. In vitro, Mel could promote the proliferation of EPCs, which protected EPCs from degeneration under LPS treatment. What is more, Mel downregulated the inflammatory response and matrix degradation of EPCs activated by NF-κB pathway through binding to its specific receptors.ConclusionThese results indicate that Mel protects the integrity of the EPs and attenuates IVDD by binding to the Mel receptors in the EPs. It may alleviate the inflammatory response and matrix degradation of EPCs activated by NF-κB pathway.

Ultrashort Time-to-Echo MRI of the Cartilaginous Endplate: Technique and Association with Intervertebral Disk Degeneration

2012 ◽  
Vol 2 (1_suppl) ◽  
pp. s-0032-1319972-s-0032-1319972
Author(s):  
T. Law ◽  
M. P. Anthony ◽  
D. Samartzis ◽  
Q. Chan ◽  
M. Kim ◽  
...  
Keyword(s):  
Intervertebral Disk ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration ◽  
Cartilaginous Endplate

Combination of MRI and 99mTc-NTP 15-5 Scintigraphy for the Assessment of Intervertebral Disk Degeneration and Tissue Engineering

2012 ◽  
Vol 2 (1_suppl) ◽  
pp. s-0032-1319873-s-0032-1319873
Author(s):  
P. Colombier ◽  
J. Clouet ◽  
E. Miot-Noirault ◽  
A. Vidal ◽  
F. Cachin ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Intervertebral Disk ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration

scholarly journals Raloxifene retards the progression of adjacent segmental intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus in ovariectomized rats

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Qi Sun ◽  
Xin-Yu Nan ◽  
Fa-Ming Tian ◽  
Fang Liu ◽  
Shao-Hua Ping ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Lumbar Fusion ◽  
B Cell Lymphoma ◽  
Intervertebral Disk ◽  
Ovariectomized Rats ◽  
Tunel Staining ◽  
Mineral Density ◽  
Vertebral Osteoporosis ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration

Abstract Background Adjacent segmental intervertebral disk degeneration (ASDD) is a major complication secondary to lumbar fusion. Although ASSD pathogenesis remains unclear, the primary cause of intervertebral disk degeneration (IVDD) development is apoptosis of nucleus pulposus (NP). Raloxifene (RAL) could delay ASDD by inhibiting NP apoptosis. Methods An ASDD rat model was established by ovariectomy (OVX) and posterolateral spinal fusion (PLF) on levels 4–5 of the lumbar vertebrae. Rats in the treatment groups were administered 1 mg/kg/d RAL by gavage for 12 weeks, following which, all animals were euthanized. Lumbar fusion, apoptosis, ASDD, and vertebrae micro-architecture were evaluated. Results RAL maintained intervertebral disk height (DHI), delayed vertebral osteoporosis, reduced histological score, and inhibited apoptosis. The OVX+PLF+RAL group revealed upregulated expression of aggrecan and B-cell lymphoma-2 (bcl2), as well as significantly downregulated expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), metalloproteinase-13 (MMP-13), caspase-3, BCL2-associated X (bax), and transferase dUTP nick end labeling (TUNEL) staining. Micro-computed tomography (Micro-CT) analysis revealed higher bone volume fraction (BV/TV), bone mineral density (BMD), and trabecular number (Tb.N), and lower trabecular separation (Tb.Sp) in OVX+PLF+RAL group than in the OVX+PLF group. Conclusions RAL can postpone ASDD development in OVX rats through inhibiting extracellular matrix metabolic imbalance, NP cell apoptosis, and vertebral osteoporosis. These findings showed RAL as a potential therapeutic target for ASDD.

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