Canine models of spine disorders

Abstract

Neck and low back pain are common among the adult human population and impose large social and economic burdens on health care and quality of life. Spine-related disorders are also significant health concerns for canine companions with etiopathogeneses, clinical presentations, and diagnostic and therapeutic options that are very similar to their human counterparts. Historically, induced and spontaneous pathology in laboratory rodents, dogs, sheep, goats, pigs, and nonhuman primates have been used for study of human spine disorders. While each of these can serve as useful preclinical models, they all have inherent limitations. Spontaneously occurring spine disorders in dogs provide highly translatable data that overcome many of the limitations of other models and have the added benefit of contributing to veterinary healthcare as well. For this scoping review, peer-reviewed manuscripts were selected from PubMed and Google Scholar searches using keywords: "intervertebral disc," "intervertebral disc degeneration," "biomarkers," "histopathology," "canine," and "mechanism." Additional keywords such as "injury," "induced model," and "nucleus degeneration" were used to further narrow inclusion. The objectives of this review were to (a) outline similarities in key features of spine disorders between dogs and humans; (b) describe relevant canine models; and (c) highlight the applicability of these models for advancing translational research and clinical application for mechanisms of disease, diagnosis, prognosis, prevention, and treatment, with a focus on intervertebral disc degeneration. Best current evidence suggests that dogs share important anatomical, physiological, histological, and molecular components of spinal disorders in humans, such that induced and spontaneous canine models can be very effective for translational research. Taken together, the peer-reviewed literature supports numerous advantages for use of canine models for study of disorders of the spine when the potential limitations and challenges are addressed.

Keywords: canine research models; intervertebral disc degeneration; spine pathology; spine‐related disorders.

FIGURE 1

Biomechanical‐Biology of IVD cycle. Schematic depicting the main and peripheral features of cellular changes, impaired matrix metabolism, and altered biomechanics and their role in the degenerating intervertebral disc

FIGURE 2

Sagittal and dorsal plane T2‐weighted MRI sequences of the thoracolumbar spine of a chondrodystrophic dog with symptomatic IVD extrusion. There is a heterogenous, extradural mass effect (arrow heads) causing compression of the spinal cord and loss of the epidural fat and subarachnoid signal at T12 to T13. There is absence of disc signal within the disc space (arrow). This is verified on the dorsal plane image with the extruded disc seen along the left side of the spinal canal, compressing the spinal cord and deviating the cord and subarachnoid signal to the right (R)

FIGURE 3

Sagittal reformatted CT image of the lumbosacral spine of a dog with lumbosacral instability and IVD disease. There is “stairstepping” (arrow heads) of the vertebral canal at the L7 to S1 junction with laminar impingement (arrow) causing deviation of the thecal sac within the canal. There is narrowing of the disc space with disc protrusion, wedging of the disc space (W), and incomplete osseous spondylosis deformans ventrally (*)

FIGURE 4

Lateral cervical spine radiographic views of a Doberman Pinscher with neurologic signs localized to the caudal cervical spine. There are subtle changes at the ventral margin of the cranial endplates at C5, C6, and C7. Lateral myelogram showing compression of the subarachnoid space/contrast column at C5 to C6 and C6 to C7 (arrow heads), and dorsal compression at C4 to C5, C5 to C6, and C6 to C7 (arrows)

FIGURE 5

Representative images of healthy canine intervertebral discs (IVD). A, Bisected whole lumbar IVD with a gelatinous core (nucleus pulposus; NP) surrounded by rings of collagenous tissue bundles (annulus fibrosus; AF). B, Section of cervical IVD with nucleus pulposus (NP) and annulus fibrosus (AF). Scale bar = 1 mm. C,D, Higher magnification of the nucleus pulposus with large quantities of basophilic extracellular matrix populated by sheets of notochordal cells. Scale bar = 100 μm. E,F, Higher magnification of the annulus fibrosus composed of collagenous tissue bundles arranged in parallel with embedded fibrochondrocytic cells. Scale bar = 200 μm. B,C,E, H&E; D, Safranin‐O; F, Toluidine blue

FIGURE 6

Representative images of degenerative changes in human and canine intervertebral discs (IVD). A, Bisected whole human thoracic IVD from a 43‐year old male. B, Section of human lumbar IVD from the same male. The annulus fibrosus‐nucleus pulposus demarcation is completely lost. Scale bar = 1 cm. C, Tissue fissure/cleft formations (arrow) in the canine nucleus pulposus with loss of notochordal cells and cellular proliferations. Scale bar = 1 mm. D, Loss of notochordal cells and proliferation of chondrocytic‐like cells and clone formation (cell aggregates; arrow) in the canine nucleus pulposus. Scale bar = 100 μm. E, Granular debris (arrow) at the transitional zone of canine IVD. Scale bar = 100 μm. F, Loss of collagenous meshwork and replacement by increasingly hyalinized collagen fibers (*) in the canine annulus fibrosus. Scale bar = 500 μm. B‐F, H&E