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

Abstract

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.

Intervertebral disc degeneration and how it leads to low back pain

“… 93 A recent study has reviewed the extensive range of natural compounds which display anti‐inflammatory NP cell protective anti‐catabolic properties with potential roles in IVD regenerative processes. 94 …”

“…A complete coverage was considered outwith the scope of this review; however, additional information is available on these in two further studies. 94 , 227 …”

“…Further studies with functional foods and neutraceutical supplements under evaluation for their abilities to alleviate pain may also prove to be a useful non‐drug treatment for post‐menopausal back pain 93 . A recent study has reviewed the extensive range of natural compounds which display anti‐inflammatory NP cell protective anti‐catabolic properties with potential roles in IVD regenerative processes 94 …”

“…Literature reviews in PubMed and Google were used to collect information on the cited studies in Table 3 using search terms such as “IVD degeneration,” “low back pain,” “models of IVD degeneration,” “small animal models of IVD degeneration,” “large animal models of IVD degeneration.” The studies cited were selected by the authors to illustrate examples of large and small animal models of IVDD and the diversity of the models developed and was not intended to provide comprehensive coverage of all IVD models of IVDD that have so far been developed which are extensive. A complete coverage was considered outwith the scope of this review; however, additional information is available on these in two further studies 94,227 …”

“…A complete coverage was considered outwith the scope of this review; however, additional information is available on these in two further studies. 94,227 A number of rodent models have been developed to specifically assess various aspects of IVDD and the development of LBP (Table 3).…”