A percutaneous, minimally invasive annulus fibrosus needle puncture model of intervertebral disc degeneration in rabbits

Luo, T. David; Marquez-Lara, Alejandro; Zabarsky, Zachary K; Vines, Jeremy B.; Mowry, Katie C.; Jinnah, Alexander H.; Ma, Xue; Berwick, Benjamin W.; Willey, Jeffrey S.; Li, Zhongyu; Smith, Thomas L.; O’Gara, Tadhg

doi:10.1177/2309499018792715

Cited by 6 publications

(6 citation statements)

References 38 publications

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“…Prior to surgery, each rabbit was placed in right lateral recumbency, and the posterolateral aspect (over the lumbar spine) was shaved and prepped using an alternating combination of 70% alcohol and chlorhexidine. For NP-Exp and NP-Vac + NP-Exp groups the lumbar spine was approached from the left side and the technique described by Luo et al ( 26 ) was performed. Briefly, a minimally invasive transcutaneous needle puncture technique, guided by fluoroscopy, was employed using a 16G spinal needle to puncture the L2-3, L3-4, L4-5, and L5-6 intervertebral discs.…”

Section: Methodsmentioning

confidence: 99%

Immunization against nucleus pulposus antigens to accelerate degenerative disc disease in a rabbit model

Bonilla,

Sikes,

Burton

et al. 2024

Front. Vet. Sci.

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Low back pain poses a significant societal burden, with progressive intervertebral disc degeneration (IDD) emerging as a pivotal contributor to chronic pain. Improved animal models of progressive IDD are needed to comprehensively investigate new diagnostic and therapeutic approaches to managing IDD. Recent studies underscore the immune system’s involvement in IDD, particularly with regards to the role of immune privileged tissues such as the nucleus pulposus (NP) becoming an immune targeting following initial disc injury. We therefore hypothesized that generating an active immune response against NP antigens with an NP vaccine could significantly accelerate and refine an IDD animal model triggered by mechanical puncture of the disc. To address this question, rabbits were immunized against NP antigens following disc puncture, and the impact on development of progressive IDD was assessed radiographically, functionally, and histologically compared between vaccinated and non-vaccinated animals over a 12-week period. Immune responses to NP antigens were assessed by ELISA and Western blot. We found that the vaccine elicited strong immune responses against NP antigens, including a dominant ~37 kD antigen. Histologic evaluation revealed increases IDD in animals that received the NP vaccine plus disc puncture, compared to disc puncture and vaccine only animals. Imaging evaluation evidenced a decrease in disc height index and higher scores of disc degeneration in animals after disc punctures and in those animals that received the NP vaccine in addition to disc puncture. These findings therefore indicate that it is possible to elicit immune responses against NP antigens in adult animals, and that these immune responses may contribute to accelerated development of IDD in a novel immune-induced and accelerated IDD model.

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Section: Methodsmentioning

confidence: 99%

Immunization against nucleus pulposus antigens to accelerate degenerative disc disease in a rabbit model

Bonilla,

Sikes,

Burton

et al. 2024

Front. Vet. Sci.

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“…10,11 Various animal models of IDD have been described, with rodent models commonly employed due to low cost, ease of genetic manipulation, and abundant biological research resources. [12][13][14] In rats, both lumbar and caudal (tail) intervertebral discs (IVDs) have been used to model IDD. [15][16][17][18][19][20][21] While caudal discs are accessible without significant surgical exposure, it is unclear whether they can reliably model the biologic environment of the lumbar spine.…”

Section: Introductionmentioning

confidence: 99%

“…Various animal models of IDD have been described, with rodent models commonly employed due to low cost, ease of genetic manipulation, and abundant biological research resources 12–14 . In rats, both lumbar and caudal (tail) intervertebral discs (IVDs) have been used to model IDD 15–21 .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Background: Previous animal models of intervertebral disc degeneration (IDD) rely on open surgical approaches, which confound the degenerative response and pain behaviors due to injury to surrounding tissues during the surgical approach. To overcome these challenges, we developed a minimally invasive percutaneous puncture procedure to induce IDD in a rat model.Methods: Ten Fischer 344 male rats underwent percutaneous annular puncture of lumbar intervertebral discs (IVDs) at L2-3, L3-4, and L4-5. Ten unpunctured rats were used as controls. Magnetic resonance imagings (MRIs), serum biomarkers, and behavioral tests were performed at baseline and 6, 12, and 18 weeks post puncture. Rats were sacrificed at 18 weeks and disc histology, immunohistochemistry, and glycosaminoglycan (GAG) assays were performed.Results: Punctured IVDs exhibited significant reductions in MRI signal intensity and disc volume. Disc histology, immunohistochemistry, and GAG assay results were consistent with features of IDD. IVD-punctured rats demonstrated significant changes in pain-related behaviors, including total distance moved, twitching frequency, and rearing duration.Conclusions: This is the first reported study of the successful establishment of a reproducible rodent model of a percutaneous lumbar annular puncture resulting in discogenic pain. This model will be useful to test therapeutics and elucidate the basic mechanisms of IDD and discogenic pain.

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“…As expected, animal models of intervertebral disc degeneration play an increasingly crucial part in clarifying pathomechanism and testing novel therapeutic strategies [6]. Animal models range from small rodents such as mice [7] to rats [8], rabbits [9], dogs [10], goats [11], sheep [12], and primates [13,14]. In addition, referring to the mechanisms, these models can be divided into three types: spontaneous models, mechanical models and structural models.…”

Section: Introductionmentioning

confidence: 99%

“…As its simplicity and less damage, the needle puncture method to obtain the experimental animal model of disc degeneration has been widely adopted. The rst needle puncture animal model was used in rabbits in 2005 [9,15,16]. Whereas, the rst needle puncture rat model was in 2008 [17], but mainly in rat caudal disc.…”

Section: Introductionmentioning

confidence: 99%

A Novel Extreme Lateral Approach for Needle Puncture Model of Lumbar Disc Degeneration in SD Rats.

Cheng

Zeng

et al. 2021

Preprint

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Background: Various animal models have been proposed to investigate several aspects of intervertebral disc degeneration (IDD). As for needle puncture model, literatures have mentioned the needle puncture in percutaneous posterolateral approach, anterior ventral approach. Our research is mean to describe a novel, extreme lateral invasive approach without posterior paraspinal muscle for needle puncture rat model.Methods: 16 adult female SD rats aging 12 weeks old was used to perform this research, which was randomly divided into two groups. We used the extreme lateral approach from the skin to lumbar intervertebral disc and advancing the 18G needle into the intervertebral disc in the experimental group and without needle puncture in the control group. Disc degeneration was confirmed by magnetic resonance imaging (MRI)and histologic evaluation.Results: All rats survived the duration of the experiment. 60 days after operation, the puncture discs of experimental group showed a significant decrease of signal intensity in the T2-weighed magnetic resonance imaging comparing with the control discs of control group. Histological analysis demonstrated the boundary between the nucleus pulposus (NP) and annulus fibrosus (AF) was not distinct, even the connective tissue nearly replaced the position of NP and proteoglycan content decreased within the punctured discs compared to the control discs. Histological score showed statistical significant difference between injury discs and control discs.Conclusions: Our study demonstrated a novel, reliable and safe approach for the needle puncture model of lumbar disc degeneration in SD rats, which provides a potential experimental model for the research on IDD without posterior paraspinal muscle injury.

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A percutaneous, minimally invasive annulus fibrosus needle puncture model of intervertebral disc degeneration in rabbits

Abstract: The present study establishes a technique for the introduction of novel therapeutic agents to treat disc degeneration that may translate to future clinical trials.

Cited by 6 publications

References 38 publications

Immunization against nucleus pulposus antigens to accelerate degenerative disc disease in a rabbit model

Immunization against nucleus pulposus antigens to accelerate degenerative disc disease in a rabbit model

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

A Novel Extreme Lateral Approach for Needle Puncture Model of Lumbar Disc Degeneration in SD Rats.

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