Percutaneous lumbar annular puncture: A rat model to study intervertebral disc degeneration and <scp>pain‐related</scp> behavior

Wawrose, Richard A.; Couch, Brandon K.; Dombrowski, Malcom; Chen, Stephen R.; Oyekan, Anthony A.; Dong, Qing; Wang, Dong; Zhou, Chaoming; Chen, Joseph; Modali, Karthik; Johnson, Marit; Sedor‐Schiffhauer, Zachary; Hitchens, T. Kevin; Jin, Tao; Bell, Kevin; Lee, Joon Y.; Sowa, Gwendolyn; Vo, Nam

doi:10.1002/jsp2.1202

Cited by 11 publications

(10 citation statements)

References 74 publications

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“…In the study by Wawrose et al a rat model was established to investigate intervertebral disk degeneration and pain-related behavior. 31 Disk degeneration was simulated by percutaneous annular puncture.…”

Section: Discussionmentioning

confidence: 99%

Proof of concept for a biologic closure device in a rodent model with evaluation of the animals’ overall burden

Weidemann,

Strauß,

Schlottmann

et al. 2023

Preprint

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Disk herniation is a common disease in the population. In case of relevant neurologic deficits and/or pain syndrome a surgical approach is necessary. Therefore, an incision has to be made in the outer ring of the disk to remove all parts of the prolapse. To date, a reliable closure device is missing and a recurrent herniation after a pain free interval is a postoperative problem well-known in spine surgeons. The current study works on proof of concept and is the first which discusses cocoon silk as a possible closure material in intervertebral disk defects in a rat model. In addition, the burden of each animal due to the surgical procedure has been evaluated by Von Frey-filament testing and stress evaluation. The rats represented no or only minor stress response. In the filament testing the animals showed low-grade reactions in general as well. In the histological examination, inflammatory tissue response was detected directly to the silk, predominantly associated with macrophage. In some areas, cell death was visible. These reactions might be associated with remaining particles of the egg, not the silk itself. Further investigations would be necessary to overcome this problem.

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Section: Discussionmentioning

confidence: 99%

Proof of concept for a biologic closure device in a rodent model with evaluation of the animals’ overall burden

Weidemann,

Strauß,

Schlottmann

et al. 2023

Preprint

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“…Specifically, the rat IVD is hallmarked by differences in its dimensions, cell populations (predominantly notochordal cells instead of chondrogenic NP cells), endplate organization, and so forth. 25 , 27 , 57 , 58 , 59 , 60 , 61 Moreover, the model employed involves a more acute disc degeneration model rather than the commonly chronic degenerative processes involved in human discogenic pain. 58 , 62 How these differences might negatively or positively impact the therapeutic potential of a vertebral MSC transplantation strategy remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the translatability of the results in our rat model to a human scenario remains to be confirmed. Specifically, the rat IVD is hallmarked by differences in its dimensions, cell populations (predominantly notochordal cells instead of chondrogenic NP cells), endplate organization, and so forth 25,27,57–61 . Moreover, the model employed involves a more acute disc degeneration model rather than the commonly chronic degenerative processes involved in human discogenic pain 58,62 .…”

Section: Discussionmentioning

confidence: 99%

“… 23 Moreover, disc puncture has been employed in multiple animal studies as a method to induce a degenerative IVD cascade. 24 , 25 , 26 , 27 Cumulatively, these facts highlight the potential detrimental effects of intradiscal needle puncture. Finally, successful implantation of the cell product is another challenging aspect, as integration of the cell product might be limited by the high intradiscal pressure and mechanical strains imposed on the fibrocartilage joint.…”

Section: Introductionmentioning

confidence: 99%

“…A 10‐year follow‐up matched‐cohort study, highlighted that disc needle puncture as part of discography procedure accelerates disc degeneration 23 . Moreover, disc puncture has been employed in multiple animal studies as a method to induce a degenerative IVD cascade 24–27 . Cumulatively, these facts highlight the potential detrimental effects of intradiscal needle puncture.…”

Section: Introductionmentioning

confidence: 99%

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Homing of vertebral‐delivered mesenchymal stromal cells for degenerative intervertebral discs repair – an in vivo proof‐of‐concept study

et al. 2022

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Introduction Cell transplantation shows promising results for intervertebral disc (IVD) repair, however, contemporary strategies present concerns regarding needle puncture damage, cell retention, and straining the limited nutrient availability. Mesenchymal stromal cell (MSC) homing is a natural mechanism of long‐distance cellular migration to sites of damage and regeneration. Previous ex vivo studies have confirmed the potential of MSC to migrate over the endplate and enhance IVD‐matrix production. In this study, we aimed to exploit this mechanism to engender IVD repair in a rat disc degeneration model. Methods Female Sprague Dawley rats were subjected to coccygeal disc degeneration through nucleus pulposus (NP) aspiration. In part 1; MSC or saline was transplanted into the vertebrae neighboring healthy or degenerative IVD subjected to irradiation or left untouched, and the ability to maintain the IVD integrity for 2 and 4 weeks was assessed by disc height index (DHI) and histology. For part 2, ubiquitously GFP expressing MSC were transplanted either intradiscally or vertebrally, and regenerative outcomes were compared at days 1, 5, and 14 post‐transplantation. Moreover, the homing potential from vertebrae to IVD of the GFP + MSC was assessed through cryosection mediated immunohistochemistry. Results Part 1 of the study revealed significantly improved maintenance of DHI for IVD vertebrally receiving MSC. Moreover, histological observations revealed a trend of IVD integrity maintenance. Part 2 of the study highlighted the enhanced DHI and matrix integrity for discs receiving MSC vertebrally compared with intradiscal injection. Moreover, GFP rates highlighted MSC migration and integration in the IVD at similar rates as the intradiscally treated cohort. Conclusion Vertebrally transplanted MSC had a beneficial effect on the degenerative cascade in their neighboring IVD, and thus potentially present an alternative administration strategy. Further investigation will be needed to determine the long‐term effects, elucidate the role of cellular homing versus paracrine signaling, and validate our observations on a large animal model.

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Biomolecular therapies for chronic discogenic low back pain: A narrative review

Rudnik‐Jansen,

van Kruining Kodele,

Creemers

et al. 2024

JOR Spine

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Chronic low back pain caused by intervertebral disc (IVD) degeneration, also termed chronic discogenic low back pain (CD‐LBP), is one of the most prevalent musculoskeletal diseases. Degenerative processes in the IVD, such as inflammation and extra‐cellular matrix breakdown, result in neurotrophin release. Local elevated neurotrophin levels will stimulate sprouting and innervation of sensory neurons. Furthermore, sprouted sensory nerves that are directly connected to adjacent dorsal root ganglia have shown to increase microglia activation, contributing to the maintenance and chronification of pain. Current pain treatments have shown to be insufficient or inadequate for long‐term usage. Furthermore, most therapeutic approaches aimed to target the underlying pathogenesis of disc degeneration focus on repair and regeneration and neglect chronic pain. How biomolecular therapies influence the degenerative IVD environment, pain signaling cascades, and innervation and excitability of the sensory neurons often remains unclear. This review addresses the relatively underexplored area of chronic pain treatment for CD‐LBP and summarizes effects of therapies aimed for CD‐LBP with special emphasis on chronic pain. Approaches based on blocking pro‐inflammatory mediators or neurotrophin activity have been shown to hamper neuronal ingrowth into the disc. Furthermore, the tissue regenerative and neuro inhibitory properties of extracellular matrix components or transplanted mesenchymal stem cells are potentially interesting biomolecular approaches to not only block IVD degeneration but also impede pain sensitization. At present, most biomolecular therapies are based on acute IVD degeneration models and thus do not reflect the real clinical chronic pain situation in CD‐LBP patients. Future studies should aim at investigating the effects of therapeutic interventions applied in chronic degenerated discs containing established sensory nerve ingrowth. The in‐depth understanding of the ramifications from biomolecular therapies on pain (chronification) pathways and pain relief in CD‐LBP could help narrow the gap between the pre‐clinical bench and clinical bedside for novel CD‐LBP therapeutics and optimize pain treatment.

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Percutaneous lumbar annular puncture: A rat model to study intervertebral disc degeneration and pain‐related behavior

Cited by 11 publications

References 74 publications

Proof of concept for a biologic closure device in a rodent model with evaluation of the animals’ overall burden

Proof of concept for a biologic closure device in a rodent model with evaluation of the animals’ overall burden

Homing of vertebral‐delivered mesenchymal stromal cells for degenerative intervertebral discs repair – an in vivo proof‐of‐concept study

Biomolecular therapies for chronic discogenic low back pain: A narrative review

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