Table 3 Animal models of IVD degeneration and low back pain
Model size | Species | Induction method | Pros | Cons | References |
|---|---|---|---|---|---|
Small | Zebrafish | Spontaneous | Genetically modifiable, easy to house, inexpensive, ideal for IVD development studies | No BBT available, limited applicability to humans, longer time to IVDD onset. | |
Mouse | Disc puncture | Inexpensive, easy to house, well-established model, widely validated, wide range of robust and validated BBTs available, less invasive | Retains notochordal cells into adulthood, rapid healing limits degeneration severity, significantly different biomechanical and diffusion properties compared to human IVD, puncture injury can be inconsistent | ||
Transgenic mice (ex: SPARC-/-, miR-183 KO, etc.) | IVDD often occurs spontaneously, easy to house, genetic modification available, wide range of robust and validated BBTs available | More expensive than wild-type mice, often requires colony investment and genotype tracking, often has a long degeneration onset | |||
Tail looping/tail suspension | Non-invasive, cost-effective, mimics postural and mechanical load-related degeneration | slow degeneration onset, variability in individual responses, may induce additional systemic effects (e.g., circulation changes, muscle atrophy) | |||
Medium | Rat (SD or Wister) | Disc puncture | Inexpensive, easy to house, well-established model, widely validated, larger than mouse, wide range of robust and validated BBTs available, less invasive than surgical methods | Retains notochordal cells, different biomechanics and diffusion vs. humans, puncture technique and needle size influence variability in degeneration progression | 78,79,224,272,273,274,275,278,279,280,281,282,283,284,285,286,287,288,289 |
Injection | Models cell-induced pain, may better represent pain-related pathology, easy to house, inexpensive, wide range of robust and validated BBTs available, less invasive than surgical methods | Retains notochordal cells, technically challenging procedure, injection technique and needle size influence variability in degeneration progression | |||
Disc puncture with injection | Easy to house, inexpensive, wide range of robust and validated BBTs available, pain and/or degeneration can be induced independently, less invasive than surgical methods | Injected solutions such as cytokines significantly exceed natural conditions, technique and needle size influence variability in degeneration progression | |||
Spinal attachment unit | More natural induction of degeneration, easy to house, inexpensive, wide range of robust and validated BBTs available, minimal invasive | Requires specialized surgical expertise and equipment | |||
Surgically induced disc injury (ex: Nuclectomy) | Fast and severe degenerative phenotype, difficult to control Easy to house, inexpensive, wide range of robust and validated BBTs available, | Technically challenging, less accurate representation of human degeneration phenotype, invasive, increased risk of inflammation and off-target tissue damage affecting pain outcomes | |||
Rabbit | Injection | Larger disc size compared to rodents, limited BBT methods available | Expensive, requires larger housing compared to murine models, does not fully replicate natural disease progression, injection technique and needle size influence variability in degeneration progression | ||
Disc puncture with injection | Larger disc size compared to rodents, limited BBT methods available | Requires skilled surgical techniques, potential variability in injury severity, puncture/injection technique and needle size influence variability in degeneration progression | |||
Disc Puncture | Established model for degeneration studies, larger disc size compared to rodents, easier for surgical manipulation, limited BBT methods available | Requires skilled surgical techniques, Puncture technique and needle size influence variability in degeneration progression | |||
Large | Pig | Disc puncture | Well-established model for degeneration studies, BBTs exist in other fields of study, more biomechanically accurate than rodents, minimally invasive | Expensive, difficult to house, needs robust preliminary data prior to using model, retains notochordal cells into adulthood, expert required to perform BBT and analysis, puncture technique and needle size influence variability in degeneration progression | |
Surgically induced disc injury | Well-established model for degeneration studies, BBTs exist in other fields of study, more biomechanically accurate than rodents, controlled and reproducible degeneration, allows for precise lesion creation, severe fast degeneration onset | Expensive, difficult to house, needs robust preliminary data prior to using model, retains notochordal cells into adulthood, expert required to perform BBT and analysis, minimal representative of natural development of IVDD, increased risk of inflammation and off-target tissue damage affecting pain outcomes | |||
Endplate injury | Mimics early stage IVDD, more physiologically relevant, minimal damage to disc structure | Specialized equipment required to create precise endplate lesions, injury severity can be difficult to standardize across subjects, may, may cause unintended bone remodeling, may take longer for IVDD-related pain behaviors to manifest compared to other models | |||
Goat | Disc puncture | Well-established model for degeneration studies, BBTs exist in other fields of study, more biomechanically accurate than rodents, BBT methods available in other fields, minimally invasive | Expensive, hard to house, needs robust preliminary data prior to using model, expert required to perform BBT and analysis | ||
Chondrotinase ABC injection | Well-established model for degeneration studies, BBTs exist in other fields of study, more biomechanically accurate than rodents, BBT methods available in other fields, minimally invasive | Enzymatic digestion of disc non-representative of disease development, expert required to perform BBT and analysis | |||
Sheep (various breeds) | Surgically induced disc injury | Large disc size, Controlled and reproducible degeneration, allows for precise lesion creation, severe fast degeneration onset | Expensive, difficult to house, needs robust preliminary data prior to using model, limited BBT methods available in other fields, minimal representative of natural development of IVDD, invasive, increased risk of inflammation and off-target tissue damage affecting pain outcomes | ||
Disc puncture | Large disc size, severity can be somewhat controlled, minimally invasive | Expensive, difficult to house, needs robust preliminary data prior to using model, limited BBT methods available in other fields, moderate representation of natural development of IVDD | |||
Enzymatic injection (ex: Chondrotinase ABC injection) | Level of degeneration can be precisely controlled, minimally invasive | Expensive, difficult to house, needs robust preliminary data prior to using model, limited BBT methods available in other fields, enzymatic degradation does not replicate full biochemical complexity of IVDD | |||
Dog | Spontaneous | Naturally occurring IVDD, closer disc structure and degeneration process to humans | Expensive, difficult to house, slow degeneration onset, high variability in disease presentation | ||
Disc Puncture | Faster induction of IVDD, degeneration severity can be somewhat controlled | Requires specialized surgical expertise, variability in healing response | |||
Compressive loading | Mimics mechanical stress-related degeneration, non-invasive | Requires prolonged study duration, degeneration rate may be inconsistent | |||
Surgically induced disc injury | Controlled and reproducible degeneration, allows for precise lesion creation | Invasive, requires specialized surgical expertise, may not fully mimic natural IVDD progression, increased risk of inflammation and off-target tissue damage affecting pain outcomes | |||
Non-human primates | Spontaneous | Most similar to human IVDD, cellular and biomechanical similarity to humans, BBTs available | Expensive, difficult to house, requires extensive and robust positive preliminary data prior to using model, ethically challenging, longer time to IVDD onset, expert required to perform BBT and analysis | ||
Surgically induced disc injury (nucleotomy, discectomy, etc.) | Fast and severe degeneration induction compared to spontaneous, better mimics human pathology than small animal models, BBTs available | Expensive, limited availability, ethical concerns, technically challenging, less accurate representation of degeneration seen in humans, limited data on species-specific responses, expert required to perform BBT and analysis, invasive, increased risk of inflammation and off-target tissue damage affecting pain outcomes | |||
Injection (ex: saline, bleomycin, etc.) | Fast and severe degeneration induction compared to spontaneous, better mimics human pathology than small animal models, BBTs available, minimally invasive | Expensive, limited availability, ethical concerns, technically challenging, less accurate representation of degeneration seen in humans, limited data on species-specific responses, expert required to perform BBT and analysis | |||
Surgical plus injection (ex: Annulotomy + collagenase, etc.) | Fast and severe degeneration induction compared to spontaneous, better mimics human pathology than small animal models, BBTs available | Expensive, limited availability, ethical concerns, technically challenging, less accurate representation of degeneration seen in humans, limited data on species-specific responses, expert required to perform BBT and analysis, invasive, increased risk of inflammation and off-target tissue damage affecting pain outcomes | |||
Bovine (cow) | Spine motion segment | Excellent for ex vivo biomechanical studies, relatively easy and cost-effective for ex vivo studies | Does not take other anatomical structures into account, cannot be studied long term |
