Summary: The medical records of 156 dogs with degenerative lumbosacral stenosis (DLS) that underwent decompressive surgery were reviewed for signalment, history, clinical signs, imaging and surgical findings. The German Shepherd Dog (GSD) was most commonly affected (40/156, 25.6%). Pelvic limb lameness, caudal lumbar pain and pain evoked by lumbosacral pressure were the most frequent clinical findings. Radiography showed lumbosacral step formation in 78.8% (93/118) of the dogs which was associated with elongation of the sacral lamina in 18.6% (22/118). Compression of the cauda equina was diagnosed by imaging (epidurography, CT, or MRI) in 94.2% (147/156) of the dogs. Loss of the bright nucleus pulposus signal of the L7-S1 disc was found on T2-weighted MR images in 73.5% (25/34) of the dogs. The facet joint angle at L7-S1 was significantly smaller, and the tropism greater in GSD than in the other dog breeds. The smaller facet joint angle and higher incidence of tropism seen in the GSD may predispose this breed to DLS. Epidurography, CT, and MRI allow adequate visualization of cauda equina compression. During surgery, disc protrusion was found in 70.5% (110/156) of the dogs. Overall improvement after surgery was recorded in the medical records in 79.0% (83/105) of the dogs. Of the 38 owners that responded to questionnaires up to five years after surgery, 29 (76%) perceived an improvement.

Introduction: Early degeneration of the intervertebral disc (IVD) involves a change in cellular differentiation from notochordal cells (NCs) in the nucleus pulposus (NP) to chondrocyte-like cells (CLCs). The purpose of this study was to investigate the gene expression profiles involved in this process using NP tissue from non-chondrodystrophic and chondrodystrophic dogs, a species with naturally occurring IVD degeneration. Methods: Dual channel DNA microarrays were used to compare 1) healthy NP tissue containing only NCs (NC-rich), 2) NP tissue with a mixed population of NCs and CLCs (Mixed), and 3) NP tissue containing solely CLCs (CLC-rich) in both non-chondrodystrophic and chondrodystrophic dogs. Based on previous reports and the findings of the microarray analyses, canonical Wnt signaling was further evaluated using qPCR of relevant Wnt target genes. We hypothesized that caveolin-1, a regulator of Wnt signaling that showed significant changes in gene expression in the microarray analyses, played a significant role in early IVD degeneration. Caveolin-1 expression was investigated in IVD tissue sections and in cultured NCs. To investigate the significance of Caveolin-1 in IVD health and degeneration, the NP of 3-month-old Caveolin-1 knock-out mice was histopathologically evaluated and compared with the NP of wild-type mice of the same age. Results: Early IVD degeneration involved significant changes in numerous pathways, including Wnt/β-catenin signaling. With regard to Wnt/β-catenin signaling, axin2 gene expression was significantly higher in chondrodystrophic dogs compared with non-chondrodystrophic dogs. IVD degeneration involved significant down-regulation of axin2 gene expression. IVD degeneration involved significant down-regulation in Caveolin-1 gene and protein expression. NCs showed abundant caveolin-1 expression in vivo and in vitro, whereas CLCs did not. The NP of wild-type mice was rich in viable NCs, whereas the NP of Caveolin-1 knock-out mice contained chondroid-like matrix with mainly apoptotic, small, rounded cells. Conclusions: Early IVD degeneration involves down-regulation of canonical Wnt signaling and Caveolin-1 expression, which appears to be essential to the physiology and preservation of NCs. Therefore, Caveolin-1 may be regarded an exciting target for developing strategies for IVD regeneration.

Canine degenerative lumbosacral stenosis (DLSS) is a syndrome of low back pain with or without neurologic dysfunction associated with compression of the cauda equina. Most commonly occurring in medium- to large-breed dogs of middle to older age, German shepherd and working dogs are predisposed. Diagnosis is based on a combination of clinical signs, advanced imaging and ruling out other differential diagnoses. The volume of the intervertebral foramina at the lumbosacral junction is naturally reduced on extension but degenerative changes lead to a more marked reduction that can impinge the L7 nerve roots. Evidence is lacking on which to base decision-making for treatment of dogs with DLSS. However, surgical intervention may be indicated in dogs that do not respond to conservative management, or for dogs in which there is a requirement to work that prevents lifestyle adjustments. Improvements in electrodiagnosis and novel intra-discal treatments may improve the management of DLSS in the future.

Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3-7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or lumbosacral spine at about 6-8 years of age. IVD degeneration is characterized by changes in the biochemical composition and mechanical integrity of the IVD. In the degenerated IVD, the content of glycosaminoglycan (GAG, a proteoglycan side chain) decreases and that of denatured collagen increases. Dehydration leads to tearing of the annulus fibrosus (AF) and/or disc herniation, which is clinically characterized by pain and/or neurological signs. Current treatments (physiotherapy, anti-inflammatory/analgesic medication, surgery) for IVD disease may resolve neurological deficits and reduce pain (although in many cases insufficient), but do not lead to repair of the degenerated disc. For this reason, there is interest in new regenerative therapies that can repair the degenerated disc matrix, resulting in restoration of the biomechanical function of the IVD. CD dogs are considered a suitable animal model for human IVD degeneration because of their spontaneous IVD degeneration, and therefore studies investigating cell-, growth factor-, and/or gene therapy-based regenerative therapies with this model provide information relevant to both human and canine patients. The aim of this article is to review potential regenerative treatment strategies for canine IVD degeneration, with specific emphasis on cell-based strategies.