Development of a Novel Rat Intervertebral Disc Degeneration Model by Surgical Multifidus Resection–Induced Instability

Zhu, Daocheng; Miao, Zhimin; Dong, Mingwei; Lin, Jiahao; Wang, Yihan; Tian, Naifeng; Luo, Peng; Wu, Yaosen; Chen, Mochuan

doi:10.1016/j.wneu.2022.06.051

Cited by 2 publications

(8 citation statements)

References 36 publications

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“… 240 Rat and mouse multifidus resection models induce spinal instability and IVDD demonstrating the interdependence of the IVD and spinal muscles for spinal stability, flexibility and optimal weight bearing. 241 , 242 …”

Section: Animal Models Of Ivd Degeneration and ...mentioning

confidence: 99%

“…Mouse and rat models of IVDD have been developed where the IVD is left intact but the supportive paraspinal muscles receive a discrete surgical lesion. 241 , 242 This destabilizes the spine and induces degenerative changes in the IVD and emphasizes the inter‐relationship between the IVD and other spinal components in normal spinal loading. Small animal models of IVDD are also amenable to quantitative assessment of pain using facial recognition methodology 275 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 although this has also now been applied to canine and ovine studies.…”

Section: Animal Models Of Ivd Degeneration and ...mentioning

confidence: 99%

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Intervertebral disc degeneration and how it leads to low back pain

Diwan

Melrose

2022

JOR Spine

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The purpose of this review was to evaluate data generated by animal models of intervertebral disc (IVD) degeneration published in the last decade and show how this has made invaluable contributions to the identification of molecular events occurring in and contributing to pain generation. IVD degeneration and associated spinal pain is a complex multifactorial process, its complexity poses difficulties in the selection of the most appropriate therapeutic target to focus on of many potential candidates in the formulation of strategies to alleviate pain perception and to effect disc repair and regeneration and the prevention of associated neuropathic and nociceptive pain. Nerve ingrowth and increased numbers of nociceptors and mechanoreceptors in the degenerate IVD are mechanically stimulated in the biomechanically incompetent abnormally loaded degenerate IVD leading to increased generation of low back pain. Maintenance of a healthy IVD is, thus, an important preventative measure that warrants further investigation to preclude the generation of low back pain. Recent studies with growth and differentiation factor 6 in IVD puncture and multi‐level IVD degeneration models and a rat xenograft radiculopathy pain model have shown it has considerable potential in the prevention of further deterioration in degenerate IVDs, has regenerative properties that promote recovery of normal IVD architectural functional organization and inhibits the generation of inflammatory mediators that lead to disc degeneration and the generation of low back pain. Human clinical trials are warranted and eagerly anticipated with this compound to assess its efficacy in the treatment of IVD degeneration and the prevention of the generation of low back pain.

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Section: Animal Models Of Ivd Degeneration and ...mentioning

confidence: 99%

Section: Animal Models Of Ivd Degeneration and ...mentioning

confidence: 99%

Intervertebral disc degeneration and how it leads to low back pain

Diwan

Melrose

2022

JOR Spine

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“… 212 A rat multifidus transection model of IVDD shows the inter‐dependance of spinal muscles and the IVD. 213 This is a useful model which utilizes an intact IVD and shows how induction of spinal instability can initiate IVDD without violating IVD structure directly. The altered biomechanical loading on the degenerate IVD and mechanical destabilization alters cell‐ECM signaling resulting in the production of inflammatory cytokines and active MMPs which further promotes disc degenerative process.…”

Section: Animal Models Developed To Study Low Back‐painmentioning

confidence: 99%

“…Paraspinal muscles affected by IVDD are major pain centers in the spine 212 . A rat multifidus transection model of IVDD shows the inter‐dependance of spinal muscles and the IVD 213 . This is a useful model which utilizes an intact IVD and shows how induction of spinal instability can initiate IVDD without violating IVD structure directly.…”

Section: Animal Models Developed To Study Low Back‐painmentioning

confidence: 99%

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An update on animal models of intervertebral disc degeneration and low back pain: Exploring the potential of artificial intelligence to improve research analysis and development of prospective therapeutics

et al. 2023

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Animal models have been invaluable in the identification of molecular events occurring in and contributing to intervertebral disc (IVD) degeneration and important therapeutic targets have been identified. Some outstanding animal models (murine, ovine, chondrodystrophoid canine) have been identified with their own strengths and weaknesses. The llama/alpaca, horse and kangaroo have emerged as new large species for IVD studies, and only time will tell if they will surpass the utility of existing models. The complexity of IVD degeneration poses difficulties in the selection of the most appropriate molecular target of many potential candidates, to focus on in the formulation of strategies to effect disc repair and regeneration. It may well be that many therapeutic objectives should be targeted simultaneously to effect a favorable outcome in human IVD degeneration. Use of animal models in isolation will not allow resolution of this complex issue and a paradigm shift and adoption of new methodologies is required to provide the next step forward in the determination of an effective repairative strategy for the IVD. AI has improved the accuracy and assessment of spinal imaging supporting clinical diagnostics and research efforts to better understand IVD degeneration and its treatment. Implementation of AI in the evaluation of histology data has improved the usefulness of a popular murine IVD model and could also be used in an ovine histopathological grading scheme that has been used to quantify degenerative IVD changes and stem cell mediated regeneration. These models are also attractive candidates for the evaluation of novel anti‐oxidant compounds that counter inflammatory conditions in degenerate IVDs and promote IVD regeneration. Some of these compounds also have pain‐relieving properties. AI has facilitated development of facial recognition pain assessment in animal IVD models offering the possibility of correlating the potential pain alleviating properties of some of these compounds with IVD regeneration.

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Development of a Novel Rat Intervertebral Disc Degeneration Model by Surgical Multifidus Resection–Induced Instability

Cited by 2 publications

References 36 publications

Intervertebral disc degeneration and how it leads to low back pain

Intervertebral disc degeneration and how it leads to low back pain

An update on animal models of intervertebral disc degeneration and low back pain: Exploring the potential of artificial intelligence to improve research analysis and development of prospective therapeutics

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