Intradiscal injection of monosodium iodoacetate induces intervertebral disc degeneration in an experimental rabbit model

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.

Download Full-text

Developing consistently reproducible intervertebral disc degeneration at rat caudal spine by using needle puncture

Journal of Neurosurgery Spine ◽

10.3171/2009.2.spine08925 ◽

2009 ◽

Vol 10 (6) ◽

pp. 522-530 ◽

Cited By ~ 53

Author(s):

Huina Zhang ◽

Frank La Marca ◽

Scott J. Hollister ◽

Steven A. Goldstein ◽

Chia-Ying Lin

Keyword(s):

Animal Model ◽

Mr Imaging ◽

Intervertebral Disc ◽

Disc Degeneration ◽

Collagen Type ◽

Type Ii ◽

Collagen Type Ii ◽

Anulus Fibrosus ◽

Safranin O ◽

Ivd Degeneration

Object The goal in this study was to develop a convenient, less-invasive animal model to monitor progression of intervertebral disc (IVD) degeneration for future testing of new treatments for disc degeneration. Methods Level 5/6 and 7/8 IVDs of rat caudal spine were stabbed laterally with 18- or 21-gauge hypodermic needles to a depth of 5 mm from the subcutaneous surface with the aid of fluoroscopy. In vivo MR imaging studies were performed at 4, 8, and 12 weeks postsurgery to monitor progression of IVD degeneration. Histological analysis including H & E and safranin O staining, and immunohistochemical studies of collagen type II and bone morphogenetic protein receptor type II (BMPRII) were assessed at 12 weeks postsurgery. Results The 18- and 21-gauge needle–stabbed discs illustrated decreases in both the T2 density and MR imaging index starting at 4 weeks, with no evidence of spontaneous recovery by 12 weeks. Histological staining demonstrated a decreased nucleus pulposus (NP) area, and the NP–anulus fibrosus border became unclear during the progression of disc degeneration. Similar patterns of degenerative signs were also shown in both safranin O– and collagen type II–stained sections. The BMPRII immunohistochemical analysis of stabbed discs demonstrated an increase in BMPRII expression in the remaining NP cells and became stronger in anulus fibrosus with the severity of disc degeneration. Conclusions After introducing an 18- or 21-gauge needle into the NP area of discs in the rat tail, the stabbed disc showed signs of degeneration in terms of MR imaging and histological outcome measurements. Changes in BMPRII expression in this animal model provide an insight for the effectiveness of delivering BMPs into the region responsible for chondrogenesis for disc repair. This convenient, less-invasive, reproducible, and cost-effective model may be a useful choice for testing novel treatments for disc degeneration.

Download Full-text

Age-related degenerative changes and sex-specific differences in osseous anatomy and intervertebral disc height of the thoracolumbar spine

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2021.06.020 ◽

2021 ◽

Vol 90 ◽

pp. 317-324

Author(s):

Masaaki Machino ◽

Hiroaki Nakashima ◽

Keigo Ito ◽

Yoshito Katayama ◽

Tomohiro Matsumoto ◽

...

Keyword(s):

Intervertebral Disc ◽

Thoracolumbar Spine ◽

Disc Height ◽

Degenerative Changes ◽

Age Related ◽

Intervertebral Disc Height

Download Full-text

A pilot investigation of chemonucleolysis-induced intervertebral disc degeneration in the ovine lumbar spine

10.1101/384743 ◽

2018 ◽

Author(s):

Ryan Borem ◽

Joshua Walters ◽

Allison Madeline ◽

Lee Madeline ◽

Jeremiah Easley ◽

...

Keyword(s):

Mr Imaging ◽

Intervertebral Disc ◽

Sample Size ◽

Nucleus Pulposus ◽

Small Sample ◽

Interleukin 1Β ◽

Functional Spinal Unit ◽

Human Pathology ◽

Intradiscal Injection ◽

Ivd Degeneration

AbstractIntervertebral disc (IVD) degeneration (IVDD) initiates in the nucleus pulposus (NP) and is marked by elevated levels of pro-inflammatory cytokines and matrix-degrading proteases, leading to structural and functional disruption. IVDD therapeutics are currently being investigated; however, such approaches require validation using large animal models that recapitulate clinical, biochemical, and biomechanical hallmarks of the human pathology. Others have previously utilized intradiscal administration of chondroitinase-ABC (C-ABC) to initiate IVDD in the NP of sheep lumbar IVDs. While these studies examined changes in IVD height, hydration, and tissue micro-architecture, changes in biochemical content and mechanical properties were not assessed. Thus, the objective herein was to comprehensively characterize this ovine model IVDD for salient features reported in human degenerate IVDs by evaluating biochemical, biomechanical, and histological changes. Briefly, C-ABC (1U) was administered via intradiscal injection into the L1/2, L2/3, and L3/4 IVDs, and degeneration was assessed at 6- and 10-weeks via longitudinal magnetic resonance (MR) imaging. After 6 weeks, degenerative samples showed significant reductions in IVD heights (p=0.048) and MR imaging index (p=0.048), which worsened at 10 weeks. Post-mortem degenerate and controls IVDs were evaluated for differences in interleukin-1β concentration, axial and torsional functional spinal unit kinematics, and histological microarchitecture. Degenerate IVDs demonstrated significantly elevated concentrations of interleukin-1β (p=0.002). Additionally, degenerative samples showed increased creep displacement (p=0.022) and compressive stiffness’s (p=0.007) concurrent with decreased long-term elastic (p=0.007) and viscous dampening coefficients (p=0.002). Histological analysis of degenerative IVDs showed changes in microarchitecture, including derangement of the nucleus pulposus and annulus fibrosus tissue as well as cartilaginous end-plate irregularities. This pilot study demonstrated that intradiscal injection of 1U C-ABC induces significant and progressive degeneration of sheep lumbar IVDs over the time course investigated. The changes observed in this pilot’s study small sample size resemble the hallmarks of moderate to severe IVD degeneration observed in humans. Further study is warranted on a larger sample size to further validate these findings.

Download Full-text

Deep Learning Approach for Evaluating Lumbar Intervertebral Disc Degeneration: Achieving High Accurate Segmentation for Quantitative Analysis on MRI

10.21203/rs.3.rs-864336/v1 ◽

2021 ◽

Author(s):

Hua-dong Zheng ◽

Yue-li Sun ◽

De-wei Kong ◽

Meng-chen Yin ◽

Jiang Chen ◽

...

Keyword(s):

Deep Learning ◽

Lumbar Spine ◽

Intervertebral Disc ◽

Disc Degeneration ◽

Signal Intensity ◽

High Reliability ◽

Disc Height ◽

Intensity Difference ◽

Pfirrmann Grade ◽

Ivd Degeneration

Abstract Purpose: Using deep learning and image processing technology, a standardized automatic segmentation and quantitation network of lumbar disc degeneration based on T2MRI was proposed to help residents accurately evaluate the intervertebral disc (IVD) degeneration.Materials and Methods: A semantic segmentation network (BianqueNet) consist of self-attention mechanism skip connection module and deep feature extraction module was proposed to achieve high-precision segmentation of IVD related areas. A quantitative method was used to calculate the signal intensity difference (∆SI) in IVD, average disc height (DH), disc height index (DHI), and disc height-to-diameter ratio (DHR). Quantitative ranges for these IVD parameters in a larger population was established among the 1051 MRI images collected from four hospitals around China.Results: The average dice coefficients of BianqueNet for vertebral bodies and intervertebral discs segmentation are 97.04% and 94.76%, respectively. This procedure was suitable for different MRI centers and different resolution of lumbar spine T2MRI (ICC=.874~.958). These geographic parameters of IVD degeneration have a significant negative correlation with the modified Pfirrmann Grade, while signal intensity in IVD degeneration had excellent reliability according to the modified Pfirrmann Grade (macroF1=90.63%~92.02%).Conclusion: we developed a fully automated deep learning-based lumbar spine segmentation network, which demonstrated strong versatility and high reliability to assist residents on IVD degeneration evaluating by means of IVD degeneration quantitation.Implication for Patient Care: Deep learning–based approaches have the potential to maximize diagnostic performance for detecting disc degeneration and assessing risk of disc herniation while reducing subjectivity, variability, and errors due to distraction and fatigue associated with human interpretation.

Download Full-text

Micro-CT evaluation of asymmetrical ovine intervertebral disc height loss from surgical approach

European Spine Journal ◽

10.1007/s00586-017-5024-8 ◽

2017 ◽

Vol 26 (8) ◽

pp. 2031-2037 ◽

Cited By ~ 1

Author(s):

Christopher Ludtka ◽

Stefan Schwan ◽

Andrea Friedmann ◽

Walther Brehm ◽

Ingo Wiesner ◽

...

Keyword(s):

Intervertebral Disc ◽

Surgical Approach ◽

Disc Height ◽

Height Loss ◽

Micro Ct ◽

Intervertebral Disc Height ◽

Ct Evaluation

Download Full-text

Selection of the Optimal Puncture Needle for Induction of a Rat Intervertebral Disc Degeneration Model

January 2018 - Pain Physician ◽

10.36076/ppj/2019.22.353 ◽

2019 ◽

Vol 4 (22;4) ◽

pp. 353-360

Author(s):

Jun Zou

Keyword(s):

Animal Model ◽

Intervertebral Disc ◽

Optimal Choice ◽

Mri Imaging ◽

Needle Size ◽

Puncture Needle ◽

Model Study ◽

Magnetic Resonance Imaging Mri ◽

Underlying Mechanisms ◽

Ivd Degeneration

Background: The incidence of intervertebral disc (IVD) degeneration has increased in recent years. A simple, reliable, and reproducible animal model is critical for understanding the underlying mechanisms of IVD degeneration. The caudal discs of rats have been proposed as a common puncture model in which to induce IVD degeneration. However, there is still no consensus on the size of needle to be used. Objectives: The present study aimed to identify the appropriate needle size to establish an IVD degeneration model. Study Design: A randomized, experimental trial. Setting: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, China. Methods: Validity was verified by magnetic resonance imaging (MRI) and histology. Results: From T2-weighted MRI imaging and histological examination, the IVD punctured by the 16-gauge needle degenerated acutely one week after the operation, whereas the 26-gauge needle puncture did no harm to the IVD. An 18-gauge needle showed a progressive degeneration in IVD. Limitations: The observation period was not very long (4 weeks). Conclusions: An 18-gauge needle can be used to induce IVD degeneration in rats. Therefore, an 18-gauge needle is the optimal selection to establish the degenerative IVD model on rats, whereas the 26-gauge needle failed to cause IVD degeneration. Thus, to study the prevention and treatment of IVD degeneration, a 26-gauge needle can be used for IVD injection of growth factors, plasmids, and drugs. A 16-gauge needle may be used to induce acute disc injury, but not IVD degeneration. Key words: Low back pain, degenerative intervertebral disc, animal model, puncture needle, rat model, optimal choice

Download Full-text

Intervertebral Disc Degenerative Changes after Intradiscal Injection of TNFα in a Porcine Model

Global Spine Journal ◽

10.1055/s-0034-1376623 ◽

2014 ◽

Vol 4 (1_suppl) ◽

pp. s-0034-1376623-s-0034-1376623

Author(s):

R. Kang ◽

H. Li ◽

S. Ringgaard ◽

K. Rickers ◽

L. Xie ◽

...

Keyword(s):

Intervertebral Disc ◽

Porcine Model ◽

Degenerative Changes ◽

Intradiscal Injection

Download Full-text

Bioactive lipids in intervertebral disc degeneration and its therapeutic implications

Bioscience Reports ◽

10.1042/bsr20192117 ◽

2019 ◽

Vol 39 (10) ◽

Author(s):

Undurti N. Das

Keyword(s):

Intervertebral Disc ◽

Mapk Pathway ◽

Mitogen Activated Protein Kinase ◽

Dependent Manner ◽

Bioactive Lipids ◽

Nucleus Pulposus Cells ◽

Jnk Pathway ◽

Anti Inflammatory ◽

Ivd Degeneration ◽

Inflammatory Molecules

Abstract Intervertebral disc (IVD) degeneration is not uncommon. It is estimated that approximately >60% of individuals above the age of 40 years suffer from IVD degeneration. Shan et al. showed that hyperglycemia can enhance apoptosis of anulus fibrosis cells in a JNK pathway and p38 mitogen-activated protein kinase (MAPK) pathway dependent fashion. Recent studies showed that IVD degeneration could be an inflammatory condition characterized by increased production of matrix metalloproteinases, TNF-α, nitric oxide, IL-6, IL-17, IL-9, and prostaglandin E2, and decreased formation of anti-inflammatory molecules such as lipoxin A4. This imbalance between pro- and anti-inflammatory molecules seem to activate JNK pathway and p38 MAPK pathway to induce apoptosis of anulus fibrosis and nucleus pulposus cells. The activation of production of PGE2 (due to activation of COX-2 pathway) seems to be dependent on p38/c-Fos and JNK/c-Jun activation in an AP-1-dependent manner. These results imply that suppressing pro-inflammatory events in the disc by either augmenting anti-inflammatory events or suppressing production of pro-inflammatory molecules or both may form a logical step in the prevention and management of IVD degeneration.

Download Full-text