Quantitative sensory testing in canine musculoskeletal pain: Findings from a systematic review, meta-analysis feasibility assessment, and limitations.

Quantitative sensory testing (QST) allows the study of pain mechanisms, patient phenotyping, and response to therapy. The goals of this study were to conduct a systematic review of the use of QST in dogs with musculoskeletal disease including osteoarthritis (OA), and to assess, by means of a meta-analysis, the ability of QST to differentiate affected dogs from healthy controls. The study protocol was registered; three bibliographic databases were screened. Studies involving QST in healthy dogs and those with musculoskeletal disease were included. Data were extracted using a standardized form. Assessment of quality and risk of bias were performed using the CAMARADES critical assessment tool. Twenty-nine articles met the inclusion criteria [systematic review (n = 11); meta-analysis (n = 28)]. In the systematic review, ten studies performed static QST: mechanical [punctate tactile (n = 6); mechanical pressure (n = 5)]; thermal [cold (n = 3); hot (n = 4)]; electrical (n = 1); and one study performed dynamic QST [conditioned pain modulation (n = 1)]. Most studies were of good scientific quality and showed low to moderate risk of bias. A meta-analysis was not possible due to numerous and severe issues of heterogeneity of data among studies. Methods to reduce risk of bias and use of reporting guidelines are some of the most needed improvements in QST research in dogs. Standardization of QST methodology is urgently needed in future studies to allow for data synthesis and a clear understanding of the sensory phenotype of dogs with and without chronic pain including OA.

An update on mobility assessment of dogs with musculoskeletal disease.

Mobility impairments associated with musculoskeletal diseases, such as osteoarthritis and degenerative joint disease, affect approximately 200,000 dogs annually and pose a notable challenge to canine health and welfare. Osteoarthritis causes the remodelling of synovial joints, alongside inflammation and impaired mechanical function which can be extremely debilitating. Secondary osteoarthritis commonly affects dogs and can be exacerbated by previous joint abnormalities, such as patellar luxation or cranial cruciate ligament rupture. Although musculoskeletal diseases can affect dogs of any age, the early subtle signs of gait abnormalities are perhaps missed by owners, thus, dogs may be in the latter stages of osteoarthritis progression when they are presented to veterinarians. Dogs showing subtle signs of gait abnormalities must be presented to veterinary practices for acute diagnosis to prevent long-term deterioration. Musculoskeletal diseases, such as osteoarthritis and degenerative joint disease, are commonly diagnosed via visible radiographic changes. However, veterinarians can use a combination of subjective and objective clinical scoring systems, such as clinical metrology instruments and gait assessment in conjunction with radiography to aid their diagnosis and longitudinal monitoring of musculoskeletal diseases. These scoring systems may be more sensitive to earlier signs of mobility impairments in dogs, ultimately, promoting increased canine health and welfare by enabling pain reduction, improvement of muscle strength and preservation of joint function. Current canine mobility scoring systems available to veterinarians will be discussed in turn throughout this review for implementation into clinical practice.

A pilot study of microRNA assessment as a means to identify novel biomarkers of spontaneous osteoarthritis in dogs.

MicroRNAs (miRNAs) are important regulators of intercellular signaling and are promising biomarkers in osteoarthritis (OA). In this study, comprehensive analysis was performed to identify miRNAs involved in the pathogenesis of spontaneous OA in dogs. Dogs diagnosed with OA based on radiography and arthroscopy of the stifle joint were included in the OA group. Dogs without any evidence of orthopedic disease were included in the unaffected group. To investigate miRNA expression levels, RNA sequencing analysis (RNA-seq) was performed in synovial tissue (OA group: n = 3, Unaffected group: n = 3) and RT-qPCR was performed in synovial tissue, synovial fluid and serum (OA group: n = 17, Unaffected group: n = 6), and compared between the two groups. The RNA-seq results showed that 57 miRNAs were significantly upregulated and 42 were significantly downregulated in the OA group. Specifically, miR-542 and miR-543 expression levels in the synovial tissue, synovial fluid, and serum were consistently higher in the OA group than in the unaffected group, suggesting that these miRNAs may be used as biomarkers for detecting canine OA. This is the first report to comprehensively analyze the expression patterns of miRNAs in the synovial tissue of dogs with spontaneous OA.

Results of using multiplanar reconstructed CT images for assessing elbow joint osteoarthritis in dogs are consistent with results of radiographic assessment.

OBJECTIVE: To compare osteoarthritis scores assigned through radiographic evaluation of 18 anatomic regions in the elbow joint with scores assigned through evaluation of 3-D maximum intensity projection (MIP), 3-D surface rendering (TSR), and multiplanar reconstructed (MPR) CT images, and to evaluate intraobserver and interobserver agreement of radiographic and CT scoring. SAMPLE: Radiographic and CT images of 39 elbow joints in 20 dogs. PROCEDURES: Images were anonymized and graded independently by 5 observers. One observer graded 12 elbow joints 3 times. Intraobserver consistency and repeatability, interobserver agreement, consistency among methods, and bias between methods were calculated. RESULTS: The most severe changes were observed at the proximal aspect of the anconeal process, and the medial and cranial aspects of the medial coronoid process. Intraobserver consistency was moderate or better for 11/16 regions with MIP images, 11/16 regions with TSR images, 17/18 regions with MPR images, and 14/18 regions with radiographic images. Interobserver agreement was moderate or better for 5/16 regions with MIP images, 9/16 regions with TSR images, 12/18 regions with MPR images, and 6/18 regions with radiographic images. Mean scores from CT-based methods were higher than mean radiographic scores. CLINICAL RELEVANCE: Assessments of osteoarthritis severity in the elbow joints of dogs obtained by examining radiographic images were generally consistent with assessments obtained by examining CT scans. MPR scores were more consistent and more comparable to radiographic scores than were MIP or TSR scores.

An assessment of the effectiveness of hyaluronic acid and polyacrylamide hydrogel in horses with osteoarthritis: Systematic review and network meta-analysis.

For several years, hyaluronic acid (HyA) and, more recently, polyacrylamide hydrogel (PHyd) have been used to reduce lameness and pain caused by osteoarthritis. However, there is still a lack of scientific evidence of the efficacy of these substances to allow veterinary experts to make decisions about their use in horses. The objective of this study was to evaluate, through a systematic review and network meta-analysis (NMA), the efficacy of HyA, associated or not with other drugs, and PHyd in relieving lameness in horses with osteoarthritis. The searches for primary studies were conducted on four search platforms. The efficacy of HyA and PHyd was estimated through the relative risk difference method. Heterogeneity was observed in the efficacy of HyA, indicating long-term ineffectiveness of this drug when associated or not with anti-inflammatory drugs. In contrast, the results indicate that PHyd is an effective alternative therapy, with a long period of action in reducing lameness in horses with osteoarthritis. This study provides evidence that the application of PHyd and HyA is effective in reducing lameness caused by osteoarthritis in horses at different time periods, where PHyd has a longer time of action.

"You can be blind because of loving them so much": the impact on owners in the United Kingdom of living with a dog with osteoarthritis.

BACKGROUND: There is growing awareness that caring for a chronically ill pet may have a detrimental impact on their owner's quality of life. Companion animal orthopaedic disease has received little research interest in this context. Canine osteoarthritis is known to negatively affect the welfare of many dogs in the United Kingdom, but its consequences for their owners has not previously been described. The aim of this study was to use a qualitative methodology to explore the impacts on a dog owner that occur following their dog's diagnosis with osteoarthritis. Owners of osteoarthritic dogs based in the United Kingdom (UK) were recruited through veterinary practices to participate in semi-structured interview about life with their dog. Interviews were transcribed verbatim and thematic analysis was used to construct key themes. This publication describes the theme that focused on the impact(s) that the dog's condition had had on the life of their owner. RESULTS: Forty owners of 35 dogs of a range of breeds and ages were interviewed. A wide range of negative impacts on the physical, mental and financial health of owners were described. Few had any prior experience of canine osteoarthritis, and owners of young dogs appeared to be particularly affected by the diagnosis. Owners detailed increasing worry over time about their pet's condition, frequently combined with a growing need to physically assist their dog. Sometimes this led them to seek information about, and purchase, adjunctive therapies and products. The dog's reduced mobility and need for medications progressively limited their own lifestyles and ability to have time away from their pet. Owners typically described a strong bond with their dog as a motivator to provide ongoing care. CONCLUSIONS: The negative impacts on owners of caring for an osteoarthritic dog appear multi-faceted and may be sustained over many years, particularly if the dog is young at diagnosis. Owners may be highly motivated to improve their dog's mobility and to reduce the impact the condition has on their own lives, yet they may be unsure how to achieve this. Veterinary professionals should inform and support these owners as much as possible.

Investigating the Probability of Response Bias in Owner-Perceived Pain Assessment in Dogs With Osteoarthritis.

Owners' ability to recognize signs of chronic pain in dogs undergoing pharmacologic and nonpharmacologic pain interventions during a period of physical rehabilitation is not known. This study aimed to compare dogs with and without chronic pain, and to assess the relationship between explanatory factors, including the probability of owners' response bias induced by pharmacologic and nonpharmacologic pain intervention, and chronic pain in dogs with osteoarthritis (OA). Seventy-one dogs with OA were included in this observational study. Owner-perceived pain interference was measured by Canine Brief Pain Inventory (CBPI) and owner-perceived pain behavior was assessed using Helsinki Chronic Pain Index. A dichotomous variable of Helsinki Chronic Pain Index was used in regression analysis to investigate the association between chronic pain and explanatory factors (body condition, anti-inflammatory medication, animal physiotherapy consultation once or more and owners' perception of pain interfering). Seventy-five percent of the dogs had ongoing anti-inflammatory medication, 51% of were overweight and 45% had a physiotherapy consultation. Higher levels of overt pain behaviors were reported in items addressing activities. Body condition, physiotherapy consultation and medication were not associated with chronic pain. Odds ratio (OR) and 95% confidence intervals of OR for the CBPI were 1.74 (1.23-2.47) and significantly associated with chronic pain. The adjusted OR of the CBPI did not differ from the crude OR. Owner-perceived pain behavior was not confounded by the dogs' medication. Results indicated that CBPI was not mediated by the medication. The CBPI pain interference score was not associated with response bias and may be used as clinical outcome measure of chronic pain and pain-related disability in dogs with OA along a period of physical rehabilitation comprising pharmacologic and nonpharmacologic pain interventions.

Assessment of the medium- to long-term radiographically confirmed outcome for juvenile dogs with hip dysplasia treated with double pelvic osteotomy.

OBJECTIVE: To assess the medium- to long-term radiographically confirmed outcomes in juvenile dogs with hip dysplasia (HD) that did and did not undergo double pelvic osteotomy (DPO). STUDY DESIGN: Retrospective case-controlled. ANIMALS: Twenty-six dogs with HD that were candidates for DPO; 22 dogs underwent DPO (16 bilateral, six unilateral); four dogs did not. METHODS: Initial and follow-up radiographs of DPO candidates (2011-2017) that did and did not undergo surgery were reviewed, and the British Veterinary Association and Kennel Club Hip Dysplasia Scheme score (BVA-HD), osteoarthritis score (OAS) and laxity index score (LI) were determined. Baseline and follow-up BVA-HD, OAS, and change in radiographically confirmed scores were compared by using analysis of variance for correlated samples. RESULTS: There was no significant difference in BVA-HD or OAS between surgically treated and nonsurgically treated cohorts at baseline. Follow-up radiographs (median, 49 months) revealed that most (34/38) hips had a BVA-HD ≤10 after DPO, while four of eight hips from the nonsurgical cohort had BVA-HD >10. Follow-up BVA-HD and OAS were lower in hips after surgery (BVA-HD median 2.15, interquartile range [Q1-Q3] 1.3-4.1; OAS median 1.9, Q1-Q3 1.1-4.1) compared with the nonsurgically treated cohort (BVA-HD median 11.4, Q1-Q3 8.1-17.5, P < .01; OAS median 7.0, Q1-Q3 5.1-13.4, P < .01). Seven hips with an LI >1 had no radiographically confirmed progression of osteoarthritis after DPO. CONCLUSION: Double pelvic osteotomy prevented radiographically confirmed progression of osteoarthritis in the medium- to long-term. Laxity index score > 1 was not a contraindication for DPO in this study. CLINICAL SIGNIFICANCE: Double pelvic osteotomy prevents progression of radiographically confirmed features of osteoarthritis in juvenile dogs with HD.

Histologic assessment of age-related changes in the temporomandibular joints of horses.

OBJECTIVE: To describe histologic changes in the temporomandibular joints (TMJs) of horses of various ages. SAMPLE: 22 TMJs from cadavers of 11 horses. PROCEDURES: Horses were categorized into 3 age groups (group 1, 2 to 10 years old [n = 3]; group 2, 11 to 20 years old [3]; and group 3, > 20 years old [5]). Each TMJ was sectioned into 5-mm slices, preserved in formalin, decalcified in formic acid, and routinely processed for histologic analysis. Joints were systematically assessed by use of previously described methods. Multilevel mixed-effects models were used to examine the data. RESULTS: The number of changes was significantly fewer and degree of changes was significantly less within the TMJs of group 1 horses, compared with those of group 3 horses. Comparison among groups revealed that the combination of temporal and mandibular scores for group 1 was significantly lower than for groups 2 or 3. Disk score did not differ significantly between groups 1 and 2, but disk scores of groups 1 and 2 were significantly lower than the disk score of group 3. CONCLUSIONS AND CLINICAL RELEVANCE: The assessed lesions were associated with osteoarthritis, and they accumulated in the TMJs as horses aged. In the absence of signs of pain manifested as changes in mastication, behavior, or performance, it would be difficult to determine the point at which accrued pathological changes represented the onset of clinically important osteoarthritis of the TMJs.

Three-dimensional assessment of the influence of juvenile pubic symphysiodesis on the pelvic geometry of dogs.

OBJECTIVE To evaluate the 3-D geometry of canine pelves and to characterize the long-term effects of juvenile pubic symphysiodesis (JPS) on pelvic geometry by comparing the pelvic configuration between littermates that did and did not undergo the procedure. ANIMALS 24 Labrador Retriever, Golden Retriever, or Labrador Retriever-Golden Retriever crossbred service dogs from 13 litters. PROCEDURES At 16 weeks old, puppies with a hip joint distraction index ≥ 0.5 were randomly assigned to undergo thermal JPS (n = 9), mechanical JPS (7), or a sham (control) surgical procedure (8). Ten years later, each dog underwent a CT scan of the pelvic region. Modeling software was used to create 3-D reconstructions from the CT scans, and various pelvic measurements were made and compared among the 3 treatments. RESULTS Compared with the control treatment, thermal and mechanical JPS increased the hemipelvis acetabular angle by 4°, the acetabular angle of lateral opening by 5°, and the orientation of the medial acetabular wall in a transverse plane by 6°, which indicated that JPS increased dorsal femoral head coverage by the acetabulum. Both JPS procedures decreased the pelvic canal area by approximately 20% and acetabular inclination by 6° but did not alter acetabular retroversion. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that thermal and mechanical JPS were equally effective in altering the 3-D pelvic geometry of dogs. These findings may help guide future studies of alternatives for optimizing canine pelvic anatomy to minimize the risk of hip dysplasia and associated osteoarthritis.

Assessment of the effects of gabapentin on activity levels and owner-perceived mobility impairment and quality of life in osteoarthritic geriatric cats.

OBJECTIVE Toevaluate effects of gabapentin on activity levels and owner-perceived mobility impairment and quality of life (QOL) in osteoarthritic geriatric cats. DESIGN Blinded, placebo-controlled, randomized crossover-design study. ANIMALS 20 osteoarthritic cats (≥ 10 years old). PROCEDURES Cats received gabapentin (10 mg/kg [4.5 mg/lb]) or placebo treatment, PO, every 12 hours for 2 weeks, followed by the alternate treatment (with no washout period). Activity was assessed with a collar-mounted accelerometer. A client-specific outcome measure (CSOM) questionnaire was used weekly to collect owner assessments of 3 selected activities in which their cats had impaired mobility; QOL ratings (worse, the same, or improved) following crossover to each treatment and for the overall study period were collected at the end of the investigation. Activity counts, CSOM and QOL data, and deterioration in impaired activities (ie, decrease of ≥ 2 points in CSOM scores) associated with treatment crossover were assessed statistically. Adverse events were recorded. RESULTS Gabapentin administration was associated with significantly lower mean daily activity counts (48,333 vs 39,038 counts/d) and significantly greater odds (approx 3-fold change) of CSOM ratings indicating improvement in impaired activities, compared with results for the placebo treatment. A greater proportion of cats had deterioration in impaired activities after the crossover from gabapentin to placebo than when the opposite occurred, but the proportion of cats with worsened QOL did not differ between sequences. Adverse events were noted for 10 cats (9 that completed the study) during gabapentin treatment (sedation, ataxia, weakness, and muscle tremors) and 1 cat during placebo treatment (lethargy). CONCLUSIONS AND CLINICAL RELEVANCE Gabapentin treatment was associated with improvement in owner-identified impaired activities of osteoarthritic cats. Activity levels were lower than those during placebo treatment, and sedation was the most common adverse effect.

Assessment of effectiveness and safety of repeat administration of proinflammatory primed allogeneic mesenchymal stem cells in an equine model of chemically induced osteoarthritis.

BACKGROUND: This study aimed at assessing the effectiveness and safety of repeated administrations of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) primed with tumor necrosis factor (TNF)-α and interferon-γ in an equine model of chemically-induced osteoarthritis. Arthritis was induced in both radio-carpal (RC)-joints by amphotericin-B in 18 ponies, divided into three groups depending on the treatment injected: MSC-naïve (n = 7), MSC-primed (n = 7) and control (n = 4). The study consisted of two phases and used one RC-joint of each animal in each phase, with four months time-lapse, in order to assess two end-points. Clinical, synovial, radiological and ultrasonographic follow-up was performed. At six months, animals were euthanized and both carpi were assessed by magnetic resonance imaging (MRI), gross anatomy, histopathology, histochemistry and gene expression. RESULTS: Clinical and synovial inflammatory signs were quicker reduced in MSC-treated groups and repeated allogeneic administration did not produce adverse reactions, but MSC-primed group showed slight and transient local inflammation after second injection. Radiology and MRI did not show significant differences between treated and control groups, whereas ultrasonography suggested reduced synovial effusion in MSC-treated groups. Both MSC-treated groups showed enhanced cartilage gross appearance at two compared to six months (MSC-naïve, p < 0.05). Cartilage histopathology did not reveal differences but histochemistry suggested delayed progression of proteoglycan loss in MSC-treated groups. Synovium histopathology indicated decreased inflammation (p < 0.01) in MSC-primed and MSC-naïve at two and six months, respectively. At two months, cartilage from MSC-primed group significantly (p < 0.05) upregulated collagen type II (COL2A1) and transforming growth factor (TGF)-ß1 and downregulated cyclooxygenase-2 and interleukin (IL)-1ß. At six months, MSC-treatments significantly downregulated TNFα (p < 0.05), plus MSC-primed upregulated (p < 0.05) COL2A1, aggrecan, cartilage oligomeric protein, tissue inhibitor of metalloproteinases-2 and TGF-ß1. In synovium, both MSC-treatments decreased (p < 0.01) matrix metalloproteinase-13 expression at two months and MSC-primed also downregulated TNFα (p < 0.05) and IL-1ß (p < 0.01). CONCLUSIONS: Both MSC-treatments provided beneficial effects, mostly observed at short-term. Despite no huge differences between MSC-treatments, the findings suggested enhanced anti-inflammatory and regulatory potential of MSC-primed. While further research is needed to better understand these effects and clarify immunogenicity implications, these findings contribute to enlarge the knowledge about MSC therapeutics and how they could be influenced.

Assessment of the effects of diet and physical rehabilitation on radiographic findings and markers of synovial inflammation in dogs following tibial plateau leveling osteotomy.

OBJECTIVE To determine the effects of an omega-3 fatty acid and protein-enriched diet, physical rehabilitation, or both on radiographic findings and markers of synovial inflammation in dogs following tibial plateau leveling osteotomy and arthroscopic surgery for treatment of cranial cruciate ligament disease. DESIGN Randomized, prospective clinical trial. ANIMALS 48 dogs with unilateral cranial cruciate ligament disease. PROCEDURES Dogs were randomly assigned to receive a dry omega-3 fatty acid and protein-enriched dog food formulated to support joint health (test food [TF]), a dry food formulated for adult canine maintenance (control food [CF]), TF plus rehabilitation, or CF plus rehabilitation after surgery. Synovial fluid prostaglandin (PG) E2 and interleukin-1ß concentrations, radiographic osteoarthritis scores, osteotomy site healing, and patellar ligament thickness were assessed at predetermined time points up to 6 months after surgery. RESULTS Dogs that received CF had significantly higher PGE2 concentrations over time following surgery than did dogs that received TF, regardless of rehabilitation status. Synovial fluid interleukin-1ß concentrations did not change over time in any groups. Diet and rehabilitation were both associated with osteoarthritis scores, with significantly lower scores over time for dogs that received TF versus CF and for dogs that underwent rehabilitation versus those that did not. Proportions of dogs with complete osteotomy healing 8 and 24 weeks after surgery were significantly lower for dogs that received TF than for dogs that received CF, regardless of rehabilitation status. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that feeding the TF can result in lower synovial fluid PGE2 concentrations and that both the TF and rehabilitation can reduce progression of osteoarthritis in the 6 months following tibial plateau leveling osteotomy; clinical relevance of slower osteotomy healing in dogs fed the TF was unclear.

Translational pain assessment: could natural animal models be the missing link?

Failure of analgesic drugs in clinical development is common. Along with the current "reproducibility crisis" in pain research, this has led some to question the use of animal models. Experimental models tend to comprise genetically homogeneous groups of young, male rodents in restricted and unvarying environments, and pain-producing assays that may not closely mimic the natural condition of interest. In addition, typical experimental outcome measures using thresholds or latencies for withdrawal may not adequately reflect clinical pain phenomena pertinent to human patients. It has been suggested that naturally occurring disease in veterinary patients may provide more valid models for the study of painful disease. Many painful conditions in animals resemble those in people. Like humans, veterinary patients are genetically diverse, often live to old age, and enjoy a complex environment, often the same as their owners. There is increasing interest in the development and validation of outcome measures for detecting pain in veterinary patients; these include objective (eg, locomotor activity monitoring, kinetic evaluation, quantitative sensory testing, and bioimaging) and subjective (eg, pain scales and quality of life scales) measures. Veterinary subject diversity, pathophysiological similarities to humans, and diverse outcome measures could yield better generalizability of findings and improved translation potential, potentially benefiting both humans and animals. The Comparative Oncology Trial Consortium in dogs has pawed the way for translational research, surmounting the challenges inherent in veterinary clinical trials. This review describes numerous conditions similarly applicable to pain research, with potential mutual benefits for human and veterinary clinicians, and their respective patients.

Radiographic, Surgeon and Owner Assessment of the BioMedtrix TATE(®) Elbow Arthroplasty.

OBJECTIVE: To report the long-term radiographic and clinical outcome of the BioMedtrix TATE elbow arthroplasty system in dogs. Assessment was via radiographs, a surgeon-based questionnaire, and owner assessment of outcome using the Liverpool osteoarthritis in dogs (LOAD) and canine brief pain inventory (CBPI) questionnaires. STUDY DESIGN: Retrospective multicenter, case series. ANIMALS: Client-owned dogs undergoing TATE elbow arthroplasty. METHODS: Questionnaires were distributed to surgeons in the United Kingdom performing TATE elbow arthroplasty and to the owners of the dogs operated on. Owners completed the LOAD and CBPI questionnaires. All completed questionnaires from surgeons and owners, and radiographs of the dogs were collated and analyzed. RESULTS: Surgeon questionnaires and radiographs were obtained for 33 elbows from 32 dogs, with owner questionnaires obtained for 19 dogs. Perioperative, short-term, and mid-term complication rates were 60%, 15%, and 15%, respectively. Radiographic assessment of component alignment showed 62% of cartridges were valgus or varus malaligned and 56% of cartridges were either translated medially or laterally relative to the long axis of the ulnar. There was no significant association between component alignment and final clinical outcome. Surgeon assessment reported 24% of dogs to have full, 52% acceptable, and 24% unacceptable outcome. Owner assessment showed significant decreases in pain severity and pain interference from preoperative to final status but no change in mobility scores. CONCLUSIONS: A high complication rate and variability in component placement was recorded with TATE athroplasty. However, component malalignment did not negatively impact clinical outcome. Final clinical outcome was favorable for most cases with significant reductions in pain severity and interference scores despite no changes in mobility scores.

Comparative study of equine mesenchymal stem cells from healthy and injured synovial tissues: an in vitro assessment.

BACKGROUND: Bone marrow and adipose tissues are known sources of mesenchymal stem cells (MSCs) in horses; however, synovial tissues might be a promising alternative. The aim of this study was to evaluate phenotypic characteristics and differentiation potential of equine MSCs from synovial fluid (SF) and synovial membrane (SM) of healthy joints (SF-H and SM-H), joints with osteoarthritis (SF-OA and SM-OA) and joints with osteochondritis dissecans (SF-OCD and SM-OCD) to determine the most suitable synovial source for an allogeneic therapy cell bank. METHODS: Expression of the markers CD90, CD105, CD44, and CD34 in SF-H, SM-H, SF-OA, SM-OA, SF-OCD and SM-OCD was verified by flow cytometry, and expression of cytokeratin, vimentin, PGP 9.5, PCNA, lysozyme, nanog, and Oct4 was verified by immunocytochemistry. MSCs were cultured and evaluated for their chondrogenic, osteogenic and adipogenic differentiation potential. Final quantification of extracellular matrix and mineralized matrix was determined using AxioVision software. A tumorigenicity test was conducted in Balb-C(nu/nu) mice to verify the safety of the MSCs from these sources. RESULTS: Cultured cells from SF and SM exhibited fibroblastoid morphology and the ability to adhere to plastic. The time elapsed between primary culture and the third passage was approximately 73 days for SF-H, 89 days for SF-OCD, 60 days for SF-OA, 68 days for SM-H, 57 days for SM-OCD and 54 days for SM-OA. The doubling time for SF-OCD was higher than that for other cells at the first passage (P < 0.05). MSCs from synovial tissues showed positive expression of the markers CD90, CD44, lysozyme, PGP 9.5, PCNA and vimentin and were able to differentiate into chondrogenic (21 days) and osteogenic (21 days) lineages, and, although poorly, into adipogenic lineages (14 days). The areas staining positive for extracellular matrix in the SF-H and SM-H groups were larger than those in the SF-OA and SM-OA groups (P < 0.05). The positive mineralized matrix area in the SF-H group was larger than those in all the other groups (P < 0.05). The studied cells exhibited no tumorigenic effects. CONCLUSIONS: SF and SM are viable sources of equine MSCs. All sources studied provide suitable MSCs for an allogeneic therapy cell bank; nevertheless, MSCs from healthy joints may be preferable for cell banking purposes because they exhibit better chondrogenic differentiation capacity.

Assessment of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells in osteoarthritic dogs using a double blinded force platform analysis.

BACKGROUND: Regenerative medicine using Mesenchymal Stem Cells (MSC) alone or combined with Plasma Rich in Growth Factors (PRGF) is a rapidly growing area of clinical research and is currently also being used to treat osteoarthritis (OA). Force platform analysis has been consistently used to verify and quantify the efficacy of different therapeutic strategies for the treatment of OA in dogs including MSC associated to PRGF, but never with AD-MSC alone. The aim of this study was to use a force platform to measure the efficacy of intraarticular ADMSC administration for limb function improvement in dogs with severe OA. RESULTS: Ten lame dogs with severe hip OA and a control group of 5 sound dogs were used for this study. Results were statistically analyzed to detect a significant increase in peak vertical force (PVF) and vertical impulse (VI) in treated dogs. Mean values of PVF and VI were significantly improved within the first three months post-treatment in the OA group, increasing 9% and 2.5% body weight, respectively, at day 30. After this, the effect seems to decrease reaching initial values. CONCLUSION: Intraarticular ADMSC therapy objectively improved limb function in dogs with hip OA. The duration of maximal effect was less than 3 months.

Comparison of force plate gait analysis and owner assessment of pain using the Canine Brief Pain Inventory in dogs with osteoarthritis.

BACKGROUND: Lameness assessment using force plate gait analysis (FPGA) and owner assessment of chronic pain using the Canine Brief Pain Inventory (CBPI) are valid and reliable methods of evaluating canine osteoarthritis. There are no studies comparing these 2 outcome measures. OBJECTIVE: Evaluate the relationship between CBPI pain severity (PS) and interference (PI) scores with the vertical forces of FPGA as efficacy measures in canine osteoarthritis. ANIMALS: Sixty-eight client-owned dogs with osteoarthritis (50 hind limb and 18 forelimb). METHODS: Double-blind, randomized. Owners completed the CBPI, and dogs underwent FPGA on days 0 and 14. Dogs received carprofen or placebo on days 1 through 14. The change in PS and PI scores from day 0 to 14 were compared to the change in peak vertical force (PVF) and vertical impulse (VI). RESULTS: PS and PI scores significantly decreased in carprofen- compared with placebo-treated dogs (P = .002 and P = .03, respectively). PVF and VI significantly increased in carprofen- compared with placebo-treated dogs (P = .006 and P = .02, respectively). There was no correlation or concordance between the PS or PI score changes and change in PVF or VI. CONCLUSIONS AND CLINICAL IMPORTANCE: In these dogs with hind limb or forelimb osteoarthritis, owner assessment of chronic pain using the CBPI and assessment of lameness using FPGA detected significant improvement in dogs treated with carprofen. The lack of correlation or concordance between the change in owner scores and vertical forces suggests that owners were focused on behaviors other than lameness when making efficacy evaluations in their dogs.

Assessment of veterinary practitioners in the British Isles' approaches towards the management of canine osteoarthritis.

The aim of this questionnaire-based retrospective study was to ascertain veterinary practitioners in the British Isles' approaches to osteoarthritis in dogs. The Mann-Whitney U test, Kruskal-Wallis test and multiple ordinal logistic regression were used to compare demographic data with treatment options. Questionnaires were returned by 228 practitioners (a response rate of 22.8 per cent). The majority of responses were from males (70 per cent). Eighty-six per cent (188 of 220) of the respondents had graduated from veterinary schools in the UK and Ireland. Veterinarians who had graduated less recently used exercise modulation less frequently (P<0.004, odds ratio [OR]=1.06) and ranked exercise modulation as less important (P=0.008, OR=1.04). Veterinarians who had graduated outside the UK or Ireland were less likely (P=0.033, OR=0.46) to use exercise modulation than those who had graduated in the UK or Ireland. Veterinarians who had graduated more recently were less likely (P=0.008, OR=0.95) to use medications. Female veterinary surgeons were less likely to rank medications as important (P<0.0001, OR=0.29) and less likely to rank corticosteroids as important (P=0.046, OR=0.42) than male veterinary surgeons. Practitioners who had graduated outside the UK or Ireland were less likely (P=0.01, OR=0.30) to rank corticosteroids as important. There was a significant mild negative correlation between the frequency of use of structure-modifying osteoarthritis drugs (SMOADs) and practitioners' opinions on rank importance (-0.32, P<0.0001). Medications such as SMOADs and nutraceuticals were ranked as not important but were used frequently. Overall, age, sex, the university of graduation and the number of canine consultations per day had an impact on the practitioners' treatment protocols.