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.

Degenerative lumbar disc disease: in vivo data support the rationale for the selection of appropriate animal models

“…The lesions can be induced either ventrally or dorsolaterally to the disc and the more extensive lesions require a large surgical approach, making the procedure relatively invasive, especially in small animal models. Multiple lesions ranging from simple annular puncture with a needle (Hsieh et al, 2009;Issy et al, 2013;Kim et al, 2005;Martin et al, 2013;Masuda et al, 2004;Michalek et al, 2010;Sobajima et al, 2005;Tian et al, 2018) to extensive incision of the AF with a scalpel or drill bit (Kääpä et al, 1994;Lipson and Muir, 1980;Lipson and Muir, 1981;Melrose et al, 2002;Olsewski et al, 1996;Osti et al, 1990;Rousseau et al, 2007;Schollum et al, 2010;Zhang et al, 2011) have been described. The annular puncture can easily be guided percutaneously by fluoroscopy or CT for rabbits (Chai et al, 2016;Kim et al, 2005) or larger animals and is less invasive (Zhou et al, 2013b).…”

“…These scales are well described in DDD rodent models (Lai et al, 2015;Mosley et al, 2017). In dogs, numerous techniques have been developed such as quality of life questionnaires, quantitative sensory testing, locomotor scoring systems and kinematic gait assessments (reviewed by Thompson et al, 2018, specifically for the clinical representation of CD dogs). Furthermore, pain scales are available and have been employed in canine patients suffering DDD, including the modified Canine Brief Pain Inventory (Brown et al, 2009), which was further modified and adapted for the chronic back pain canine patients (Suwankong et al, 2007).…”

“…Interestingly, client-owned dogs also suffer DDD that is very similar to clinical entities seen in humans at the level of clinical signs, diagnostics, therapeutic approaches, histology and biochemistry. As such, the inclusion of these dogs in veterinary clinical trials could be a valuable opportunity (Bach et al, 2014;Thompson et al, 2018).…”

Fibronectin Fragments and Inflammation During Canine Intervertebral Disc Disease

“…Lower back pain is the main cause of disability in humans and therefore has a tremendous socioeconomic impact. Similarly, in dogs, IVDD is a prevalent disorder and shares many similarities in the clinical presentation, but also potentially in its aetiopathogenesis (3,4). While the molecular disease mechanisms in humans, specifically the mechanisms of inflammation during disc aging and degeneration (= inflammaging) are well-investigated (5)(6)(7)(8), considerably less is known about the pathobiology of canine IVDD.…”

Asperosaponin VI promotes human mesenchymal stem cell differentiation into nucleus pulposus like- cells via up-regulation of ERK1/2 and Smad2/3 signaling pathways.

“…IVDD is related to age, load-bearing labor, trauma and heredity and leads to chronic low back pain and economic burden [2]. Although there are many factors that can lead to LBP, IVDD is considered as a major factor [3,4]. Treatment of IVDD remains a clinical challenge due to conservative treatment, in which only symptoms can be alleviated, while surgical treatment leads to complications and structural damage [5].…”