The chondrodystrophic dog: A clinically relevant intermediate-sized animal model for the study of intervertebral disc-associated spinal pain

Abstract

Low back pain (LBP) is the leading cause of disability worldwide, with an estimated 80% of the American population suffering from a painful back condition at some point during their lives. The most common cause of LBP is intervertebral disc (IVD) degeneration (IVDD), a condition that can be difficult to treat, either surgically or medically, with current available therapies. Thus, understanding the pathological mechanisms of IVDD and developing novel treatments are critical for improving outcome and quality of life in people living with LBP. While experimental animal models provide valuable mechanistic insight, each model has limitations that complicate translation to the clinical setting. This review focuses on the chondrodystrophic canine clinical model of IVDD as a promising model to assess IVD-associated spinal pain and translational therapeutic strategies for LBP. The canine IVD, while smaller in size than human, goat, ovine, and bovine IVDs, is larger than most other small animal IVDD models and undergoes maturational changes similar to those of the human IVD. Furthermore, both dogs and humans develop painful IVDD as a spontaneous process, resulting in similar characteristic pathologies and clinical signs. Future exploration of the canine model as a model of IVD-associated spinal pain and biological treatments using the canine clinical model will further demonstrate its translational capabilities with the added ethical benefit of treating an existing veterinary patient population with IVDD.

Keywords: degeneration; pain; preclinical models.

Figure 1

Intervertebral disc (IVD) maturation from young to early and late stage IVDD where the first column shows illustrative representations throughout the stages (A‐E), middle column shows Pfirrmann grading via IVD magnetic resonance imaging (MRI) and last column showing Thompson grading of canine IVD. AF, annulus fibrosus; CEP, cartilaginous end plate; NP, nucleus pulposus. Pfirrmann grade and Thompson grade images adapted with permission from Bergknut et al. American Journal of Veterinary Research, 2011;72:899

Figure 2

Herniation of the intervertebral disc (IVD): Hansen type I (left) and type II (right) IVDD with nucleus pulposus (NP) protrusion through and AF (annulus fibrosus) rupture in type I and protrusion of AF into the vertebral canal in type II. TZ, transitional zone

Figure 3

Comparison of the healthy and degenerate human (left) and canine intervertebral disc (IVD) (right) on the gross and molecular level with neurovascular ingrowth, decreased in chondrocyte‐like cells and broken aggrecan and collagen II in the degenerate nucleus pulposus (NP)

Figure 4

Cells within the degenerate canine intervertebral disc (IVD) where nucleus pulposus (NP) tissue was surgically removed from herniated canine IVDs (A‐D); schematic of herniated IVD (a); safranin O fast staining of cell clusters in diseased disc (B) and hematoxylin and eosin staining of red blood cells in granulation tissue suggestive of angiogenesis (C); giemsa staining of mast cells (dark blue/purple, ×40) (D)