Emerging Evidence of Artemin/GFRα3 Signaling in Musculoskeletal Pain.

Chronic musculoskeletal pain is highly prevalent and poses a significant personal, societal, and economic burden. Management of chronic musculoskeletal pain remains a challenge. Long-term use of common analgesic medications such as nonsteroidal anti-inflammatory drugs and opioids is associated with adverse events, and in the case of opioids, drug addiction. Additionally, many individuals do not experience sufficient pain relief with these therapeutic approaches. Thus, there is an urgent need to develop clinically efficacious and safe therapeutics for musculoskeletal pain. Recent advances in our understanding of musculoskeletal pain neurobiology have helped identify the role of neurotrophic factors, specifically, the GDNF Family of Ligands (GFL) and their associated signaling pathways. This review outlines our current understanding of the GFL signaling systems, discusses their role in inflammatory and chronic musculoskeletal pain and sensitivity, and comments on the analgesic therapeutic potential of targeting the GFL signaling system.

Long-term follow up of 44 cats undergoing total hip replacement: Cases from a feline hip registry (2010-2020).

OBJECTIVE: To report indications, complications, and long-term outcomes following feline total hip replacement (THR) using a client-based clinical metrology questionnaire, the Feline Musculoskeletal Pain Index (FMPI), and owner satisfaction. STUDY DESIGN: Multi-institutional retrospective cohort study. ANIMALS: Cats (n = 44) that underwent THR (n = 56). METHODS: Feline THRs submitted to a registry over a 10-year period were reviewed. The FMPI and owner satisfaction surveys were used to assess outcome. RESULTS: Forty-four cats met the inclusion criteria. Median age was 2 years (range: 0.9-11), and median bodyweight 5 kg (range: 3.3-7.6). British Shorthair and Domestic Shorthair were the most frequent breeds. Most cats were neutered males (33/44) and slipped capital femoral epiphysis (SCFE) was the most common surgical indication (34/56). All implants were cemented micro and nano hip implants. Overall complications (11/56) included 9 major complications. The median duration of follow up was 752 days (range: 102-3089). No association was found between clinical variables and complications. The FMPI score improved from 0.111 (range: 0-1.222) to 2.111 (range: 0.888-3.666) postoperatively (P < .001). Owner satisfaction was reported as "very good" in 30/33 cases (90.9%). CONCLUSION: A validated client metrology questionnaire showed clinical improvement in cats following THR. The most common indication for THR in cats was SCFE occurring in young male neutered cats. Complication rates were comparable to previous reports. CLINICAL SIGNIFICANCE: Total hip replacement appears to be a successful surgical treatment for feline hip disease with very good owner satisfaction and acceptable complication rates.

2022 AAHA Pain Management Guidelines for Dogs and Cats.

These updated guidelines present a practical and logical approach to the assessment and management of acute and chronic pain in canine and feline patients. Recognizing pain is fundamental to successful treatment, and diagnostic guides and algorithms are included for assessment of both acute and chronic pain. Particularly for chronic pain, capturing owner evaluation is important, and pain-assessment instruments for pet owners are described. Expert consensus emphasizes proactive, preemptive pain management rather than a reactive, "damage control" approach. The guidelines discuss treatment options centered on preemptive, multimodal analgesic therapies. There is an extensive variety of pharmacologic and nonpharmacologic therapeutic options for the management of acute and chronic pain in cats and dogs. The guidelines include a tiered decision tree that prioritizes the use of the most efficacious therapeutic modalities for the treatment of acute and chronic pain.

Early radiation-induced oral pain signaling responses are reduced with pentoxifylline treatment.

Radiation-induced acute oral mucositis is associated with inflammation and pain. In other realms of pain research, nociceptors are known to be activated by inflammatory cytokines; for example, tumor necrosis factor alpha (TNF-α) can activate transient receptor potential ion channels on sensory neurons. But there is an unclear relationship between inflammatory cytokines and molecular mediators of pain in radiation-induced mucositis (RIM) and radiation-associated pain (RAP). In this prospective, analytical, experimental pilot study, a common drug (pentoxifylline [PTX]) was used with the goal of inhibiting TNF-α signaling in mice that underwent lingual irradiation to induce severe acute oral RIM/RAP. Body weight and glossitis scores were recorded daily. Eye wiping behaviors were assayed as a surrogate measure of oral discomfort (which is possible due to cross-sensitization of the mandibular and ophthalmic branches of the trigeminal nerve). Quantitative real-time reverse transcription polymerase chain reaction was performed on irradiated tongue tissue to measure changes in expression of TNF-α, its receptor, nuclear factor kappa-light-chain-enhancer of activated B cells, transient receptor potential vanilloid type 1 (TRPV1), and transient receptor potential vanilloid type 4 (TRPV4). Responsiveness of afferent sensory trigeminal neurons to TNF-α, a TRPV1 agonist (capsaicin), and a partial TRPV4 agonist (histamine) was measured via calcium imaging. Although PTX treatment did not reduce glossitis severity or mitigate weight loss in mice with RIM/RAP, it did inhibit the upregulation of TNF-α's receptor that normally accompanies RIM, and it also reduced neuronal responsiveness to each of the aforementioned chemical stimuli. These results provide provisional evidence that inhibition of TNF-α signaling with PTX treatment may serve as a useful tool for reducing pain in head and neck cancer patients.

Local Administration of Carboplatin in Poloxamer 407 After an Ulnar Osteosarcoma Removal in a Dog.

An 8 yr old male castrated hound presented for a left distal ulnar osteosarcoma. Staging (computed tomography and nuclear scintigraphy) did not reveal any metastases. A limb-sparing ulnectomy with local adjunctive carboplatin in a poloxamer copolymer gel (poloxamer 407) was performed. The patient recovered without complications after surgery. No wound healing complications or adverse effects occurred after local use of carboplatin in poloxamer 407. The local recurrence-free interval was 296 days from surgery, and the survival time was 445 days from initial diagnosis. This is the first report in the veterinary literature of using poloxamer 407 as a carrier for local delivery of chemotherapeutic drugs in a clinical patient.

The effectiveness of marine based fatty acid compound (PCSO-524) and firocoxib in the treatment of canine osteoarthritis.

BACKGROUND: NSAIDs are accepted as the most predictably efficacious medical treatment of the clinical signs of osteoarthritis (OA). The marine-based fatty-acid compound PCSO-524 has been proposed as an adjunctive treatment for canine OA, however benefits of this agent is still controversial. The purpose of this study was to evaluate and compare the effectiveness of PCSO-524 combined with the NSAID firocoxib using force plate gait analysis, orthopedic assessment score (OAS) and canine brief pain inventory score (CBPI) in dogs with OA. A prospective, randomized, double-blinded study was conducted. Seventy-nine dogs that had hip and/or stifle OA were assigned randomly into three treatment groups: firocoxib, PCSO-524 and combination of firocoxib and PCSO-524, orally for 4 weeks. Peak vertical force (PVF, expressed as a percentage of bodyweight), OAS, CBPI, serum prostaglandin E2 concentration, hematology and blood chemistry values were evaluated before treatment (Day0), as well as at the second (Day14) and fourth week (Day28) during treatment. RESULTS: Within group analysis revealed significant increases in PVF over the 4-week treatment period for firocoxib, PCSO-524 and the combination (p < 0.05). Mean increases in PVF were 3.25 ± 4.13, 2.01 ± 3.86, 4.11 ± 4.69%BW (mean ± SD) respectively. The OAS showed non-significant change in all treatment groups. There were significant decreases in CBPI pain severity score (PSS) and CBPI pain interference scores (PIS) within some groups over time, however no significant differences were found between the groups. Significantly decreased serum PGE2 concentration (p < 0.05) was found in the combination group. Significant increases in BUN and creatinine (p < 0.05) compared to pre-treatment values were found in the firocoxib and combination groups but not in the PCSO-524 group at day28, but all values in all dogs remained within the normal ranges. CONCLUSIONS: The results of this study suggested combination of both PCSO-524 and firocoxib is more effective in alleviation of inflammation and improvement of weight bearing ability when compared to the uses of either PCSO-524 or firocoxib alone. Further clinical studies are needed to confirm this, and to determine if there is any benefit of PCSO-524 over placebo.

Clinical measurements performed during alfaxalone total intravenous anaesthesia for radiography and neurophysiological investigations in dogs.

OBJECTIVE: To describe clinically relevant, physiological measurements collected during a 3 hour duration of alfaxalone total intravenous anaesthesia. STUDY DESIGN: Case series. ANIMALS: A total of 112 client-owned middle-aged or older dogs. METHODS: Dogs were premedicated with intramuscular acepromazine (0.03 mg kg-1). Anaesthesia was induced and subsequently maintained for up to 3 hours with alfaxalone administered intravenously. Dogs breathed 100% oxygen via an endotracheal tube. Heart rate, respiratory rate and blood pressure were evaluated 30 minutes after administration of acepromazine and used as baseline values for comparisons of intra-anaesthetic data. Blood glucose was measured 1 week prior to anaesthesia and every hour during alfaxalone anaesthesia. Quality and duration of recovery were recorded. Mean data for physiological variables were compared over three time points-before induction of anaesthesia, for the first hour of anaesthesia and from 60 minutes to discontinuation of anaesthesia. RESULTS: Mean induction dose of alfaxalone was 1.4 mg kg-1 [95% confidence interval (CI) 1.3-1.5). Post induction apnoea for >60 seconds occurred in 13 (11.6%) dogs. Mean alfaxalone infusion rate during the first 60 minutes of anaesthesia was 0.099 mg kg-1 minute-1; mean infusion rate was 0.092 mg kg-1 minute-1 from 60 minutes until discontinuation of anaesthesia. Heart rate was well maintained; hypotension (mean arterial blood pressure < 60 mmHg) was encountered in 23 (21%) dogs. Blood glucose levels did not alter during anaesthesia. Median time between discontinuation of alfaxalone infusion and extubation was 17 (7-35 minutes), time to assuming sternal recumbency was 75 (58-110 minutes), and time to standing was 109 (88-140 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone infusion provided effective anaesthesia in this population. In a minority of cases, respiratory and haemodynamic support of the patient was required.

Assessment of a novel nanoparticle hyperthermia therapy in a murine model of osteosarcoma.

OBJECTIVE: To evaluate the effects of nanoparticle hyperthermia therapy on monocyte function and tumor-derived factors associated with macrophage polarization in a murine osteosarcoma model. STUDY DESIGN: Experimental study. ANIMALS: Female C3H mice. METHODS: Peripheral blood monocyte cell surface phenotype, monocyte chemotaxis, tumor messenger RNA expression, and survival were compared among osteosarcoma (OS)-bearing mice treated with nanoparticle hyperthermia therapy, OS-bearing mice with osteomyelitis, OS-bearing mice, vehicle control mice, and normal control mice. RESULTS: OS-bearing mice with osteomyelitis had a higher proportion of "nonclassical" monocytes (Ly6Clo ) compared with all other experimental groups. There were alterations in monocyte expression of multiple chemokine receptors among experimental groups including CXCR2, CCR2, and CXCR4. Monocytes from OS-bearing mice treated with hyperthermia therapy exhibited greater chemotaxis compared with monocytes from OS-bearing mice with osteomyelitis. CONCLUSION: OS likely induced alterations in monocyte phenotype and function. Nanoparticle hyperthermia therapy increased in vitro monocyte chemotaxis. CLINICAL IMPACT: Enhancing monocyte/macrophage function in dogs with OS may enhance antitumor immunity.

Pilot evaluation of a novel unilateral onychectomy model and efficacy of an extended release buprenorphine product.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs), transdermal fentanyl patches, and transmucosal buprenorphine are probably the most commonly used options for providing post-operative analgesia in the early at-home period. However, these require daily administration or are associated with abuse concerns. One of the significant unmet needs in veterinary surgery and pain management is for longer acting opioids for cats to effectively bridge the gap between the in-hospital and at-home recovery periods. A proof of concept study of an extended release formulation of buprenorphine HCL (ER-Bup) was conducted using objective kinetic measures and a unilateral onychectomy model. Using a blinded, randomized, two period crossover design, four cats were allocated to control (saline) or ER-Bup (0.6 mg/kg, subcutaneously [SC]) treatment groups. All animals underwent a unilateral forelimb onychectomy per period with a washout/recovery period in between. Observational pain scores and kinetic data (using a pressure sensitive walkway [PSW]) were collected prior to (baseline) and at intervals for 72 h following surgery. Symmetry indices were derived for kinetic variables (peak vertical force [PVF]; vertical impulse [VI]) of each forelimb for landing following a jump and for walking. A rescue analgesic protocol was in place. Effect of surgery and treatment were evaluated using a mixed model statistical approach. RESULTS: No cats required rescue analgesics based on subjective pain score. ER-Bup had a positive influence on subjective pain scores during the 72 h postsurgery (p = 0.0473). PVF and VI of the operated limb were significantly decreased for both landing (p < 0.0001 and p < 0.0001) and walking (p < 0.0001 and p < 0.0001 respectively) compared to control. ER-Bup resulted in significantly decreased asymmetry in limb use during landing (PVF, p < 0.0001; VI, p < 0.0001) and walking (PVF, p = 0.0002, VI, p < 0.0001). The novel use of data collected following a jump from an elevated platform appeared to provide all desired information and was easier to collect than walking data. CONCLUSION: This study demonstrates that SC administration of ER-Bup may be an effective analgesic for a 72 h period postoperatively. Furthermore, landing onto a PSW from an elevated perch may be a useful and efficient way to assess analgesics in cats using a unilateral model of limb pain.

Replicate effects and test-retest reliability of quantitative sensory threshold testing in dogs with and without chronic pain.

OBJECTIVE: To evaluate replicate effects and test-retest reliability of mechanical and thermal quantitative sensory testing (QST) in normal dogs and dogs with osteoarthritis (OA)-associated pain. STUDY DESIGN: A prospective clinical study. ANIMALS: A total of 54 client owned dogs (OA, n=31; controls, n=23). METHODS: Mechanical [electronic von Frey (EVF) and blunt pressure] and thermal (hot and cold) sensory thresholds were obtained in dogs with OA-associated pain and control dogs at two visits, 7 days apart, to assess test-retest reliability. Thresholds were measured at the OA-affected joint (hip or stifle), over the tibial muscle and over the midpoint of the metatarsals. Five replicates were obtained for each modality at each site bilaterally. RESULTS: Overall, there was no significant effect of replicates on QST response. EVF thresholds were significantly lower at the second visit in OA dogs at the affected and metatarsal sites (p=0.0017 and p=0.0014, respectively). Similarly for control dogs, EVF thresholds were significantly lower at the second visit at the metatarsal site (p=0.001). Significantly higher hot thermal latencies were seen in OA dogs at the affected and tibial testing sites (p=0.014 and p=0.012, respectively), and in control dogs at the tibial site (p=0.004). CONCLUSIONS: In QST, a replicate does not show a strong effect. However, QST results show variability over time, particularly for EVF and hot thermal stimuli. CLINICAL RELEVANCE: If QST is to be used clinically to evaluate a sensitized state, the variability over time needs to be accounted for in the study design.

Pilot, randomized, placebo-controlled clinical field study to evaluate the effectiveness of bupivacaine liposome injectable suspension for the provision of post-surgical analgesia in dogs undergoing stifle surgery.

BACKGROUND: Local anesthetics are an important component of perioperative pain management, but the duration of action of available products is limited. We hypothesized that a single local infiltration of a novel bupivacaine liposome injectable suspension (AT-003) would provide clinically effective analgesia over a 72-h period. In a masked, randomized, placebo-controlled, multi-center pilot field study, dogs undergoing lateral retinacular suture placement for cranial cruciate insufficiency were randomly assigned to surgical site infiltration with AT-003 (5.3 mg/kg) or an equivalent volume of saline. Infiltration of the surgical site was done prior to closure. Primary outcome measure was the Glasgow Composite Measure Pain Scale (CMPS-SF) assessed prior to surgery and at 2, 4, 8, 12, 24, 30, 36, 48, 54, 60 and 72 h following surgery by trained individuals. Provision for rescue analgesia was employed. Repeated measures analysis of variance were utilized to test for possible differences between treatment groups and a success/failure analysis was also employed, based on the need for rescue analgesia. RESULTS: Forty-six dogs were enrolled and evaluated. For CMPS-SF scores there was a significant overall treatment effect (p = 0.0027) in favor of AT-003. There were significantly more successes in the AT-003 group compared to placebo over each time period (p = 0.0001 for 0-24 h, p = 0.0349 for 0-48 h, and p = 0.0240 for 0-72 h). No significant adverse events were seen. CONCLUSIONS: AT-003 (bupivacaine liposome injectable suspension) provided measurable local analgesia over a 72-h period following post-stifle surgery surgical site tissue infiltration. Further work is indicated to develop this product for clinical use.

A canine-specific anti-nerve growth factor antibody alleviates pain and improves mobility and function in dogs with degenerative joint disease-associated pain.

BACKGROUND: There is a critical need for proven drugs other than non-steroidal anti-inflammatory drugs for treatment of degenerative joint disease (DJD) pain in dogs. Antibodies against nerve growth factor (NGF) are analgesic in rodent models and in humans with DJD. This pilot study aimed to evaluate the efficacy of a novel caninised anti-NGF antibody (NV-01) for the treatment of DJD pain in dogs. In a randomized, parallel group, stratified, double masked, placebo controlled, proof of principle clinical pilot study design, 26 dogs with DJD received NV-01 (200 mcg/kg IV) or placebo on day 0 (D0). In addition to objective accelerometry measures, owners completed clinical metrology instruments (Client-Specific Outcome Measures [CSOM], Canine Brief Pain Inventory [CBPI] and Liverpool Osteoarthritis in Dogs Index [LOAD]) on D0, D14 and D28. CBPI subscales (pain severity [PS] and pain interference [PI]), CSOM and LOAD scores were evaluated within and between groups for change over time. Recognized success/failure criteria were applied and success compared between groups. RESULTS: CBPI PS and PI scores significantly improved in the NV-01 group (PS: D0-14, P = 0.012 and D0-28, P = 0.019; PI: D0-14, P = 0.012 and D0-28, P = 0.032) but not in the placebo group. CSOM scores showed similar patterns with a significant difference between within-group changes at D14 and D28 (P = 0.038 and P = 0.009, respectively), and significantly more successes at D28 (P = 0.047). LOAD scores significantly improved in the NV-01 group (D0-14, P = 0.004 and D0-28, P = 0.002) but not in the placebo group. There were significant differences between the groups for change in LOAD score at D14 (P = 0.014) and D28 (P = 0.033). No side effects were noted. Activity in the NV-01 group increased over the study period compared to placebo (P = 0.063) and the difference between the groups for change in activity over the time period 9am-5pm (8 hours) was significant (P = 0.006). CONCLUSIONS: These pilot data demonstrate a positive analgesic effect of anti-NGF antibody in dogs suffering from chronic pain. The magnitude of the effect appeared identical to that expected with an NSAID.

Relationship between mechanical thresholds and limb use in dogs with coxofemoral joint oa-associated pain and the modulating effects of pain alleviation from total hip replacement on mechanical thresholds.

OBJECTIVES: To compare von Frey mechanical quantitative sensory thresholds (mQSTvF ) between pelvic limbs in dogs before unilateral total hip replacement (THR) surgery; to correlate ground reaction forces (GRF) with mQSTvF ; to assess changes in mQSTvF after THR surgery. STUDY DESIGN: Prospective clinical study. ANIMALS: Dogs (n = 44). METHODS: mQSTvF and GRF measured using a pressure sensitive walkway were evaluated before, and 3, 6, and 12 months after, unilateral THR. Measurements were recorded from the affected (operated) pelvic limb (APL) and the non-operated pelvic limb (NPL). Random effects analysis and forwards stepwise linear regression models were used to evaluate the influence of time since surgery and patient factors on mQSTvF thresholds. RESULTS: There were no significant correlations between mQSTvF data and age, bodyweight or the GRF variables. Preoperative mQSTvF measured at the APL and NPL did not differ (P = .909). mQSTvF thresholds increased significantly after 12 months in NPL (P = .047) and APL (P = .001). In addition to time, APL mQSTvF values were significantly affected by sex (higher in males, P = .010) and body condition score (higher in leaner dogs, P = .035) and NPL mQSTvF values by sex (P = .038). CONCLUSION: Successful unilateral THR results in decreased central sensitization after 12 months.

Learning confounds algometric assessment of mechanical thresholds in normal dogs.

OBJECTIVE: To perform algometric readings in normal dogs in a design that would assess possible confounding factors. STUDY DESIGN: Prospective study. ANIMALS: Skeletally mature spayed female, intact male and castrated male retriever or retriever mix dogs without orthopedic or neurologic disease (n = 19). METHODS: Twelve common surgical sites were selected for algometric pressure testing. Threshold response was defined as a conscious recognition of the stimulus, and recorded in Newtons. Sites were tested in the same order, and the testing sequence repeated 3 times on each side of the dog. Dogs were tested in the morning and evening of the same day and was repeated 10-14 days later, allowing 4 separate data collections for each dog. RESULTS: Data were analyzed using ANOVA or ANCOVA. When all the data were included in the analysis, dog (P < .0001), order (P < .0001), site (P < .0001), site order (P = .0217), time (P < .0001), day (P < .0001) and repetition (P < .0001) all significantly affected the algometer readings. When only the first reading for each site was included in the analysis, dog (P < .0001), site (P < .0001) and sex (P < .0001) all significantly affected algometer readings. CONCLUSION: These results suggest that learning occurred over repeated collection time points, with dogs anticipating the stimulus and reacting at lower thresholds.

Biomechanical evaluation of the influence of an intramedullary pin on the stability of a feline ilial fracture model stabilized with a bone plate.

OBJECTIVE: To compare the mechanical properties of feline ilial fractures stabilized with either a plate (P), or a plate and IM pin (P + P). STUDY DESIGN: Mechanical study. SAMPLE POPULATION: Cadaveric cat pelvii (n = 10). METHODS: Feline ilial fractures (n = 20) stabilized with either P or P + P were subjected to 100 nondestructive load cycles, then loaded to failure. Deformation after cycling, yield load and displacement, stiffness and load at 2 mm of displacement were compared between groups. RESULTS: There were no significant differences between groups for any of the parameters. Variability of data was much larger for the P + P group. CONCLUSIONS: No biomechanical advantage was demonstrated. The P + P constructs were not significantly stronger than plates alone in this acutely loaded cadaveric model.

Current attitudes regarding the use of perioperative analgesics in dogs and cats by Brazilian veterinarians.

OBJECTIVE: To correlate the demographic data of Brazilian veterinarians with their use of, attitudes towards, knowledge of and preference for continuing education regarding use of analgesics in small animal practice. STUDY DESIGN: Prospective survey. METHODS: The questionnaire was composed of sections pertaining to demographics, personal data, use of analgesics in general and specific procedures, analgesia used, and attitudes towards the assessment and relief of pain. The descriptive statistics with frequency analysis was performed using sas for Windows 9.1.3. Chi-square for simple comparisons test was used. RESULTS: Questionnaires were obtained from 1298 small animal veterinarians. Women and younger graduates attributed higher pain scores than men and older graduates but the frequency and duration of analgesic treatment did not differ between genders. The most commonly used opioids were tramadol (79%) and morphine (51%). NSAIDs of choice were meloxicam (81%) and ketoprofen (70%). Cats received lower pain scores for laparotomy, orchiectomy and dental procedures than dogs. Practical experience (64%) and national (47%) and regional meetings (43%) were the main sources of information for identifying and treating pain in small animals. CONCLUSIONS: Although the number of Brazilian veterinarians believed that their knowledge in the area was lower than in other countries, the focus in pain management was similar or higher than in other countries, showing a good attitude in pain relief in animals.

Conservative management of canine cleft palate can be a viable treatment option: 65 cases (2006-2023).

OBJECTIVE: To evaluate nonsurgical management outcomes of cleft palate (CP) in dogs and identify any association between cleft size, prevalence of clinical signs, and quality of life (QoL). METHODS: 65 dogs treated conservatively for CP from January 2006 through December 2023 were retrospectively identified. Diet, activity, medical history, and QoL were recorded for dogs that survived to the transition to solid food. Results were compared to those from 24 control dogs. Measurements of cleft area, width, and percentage of the hard palate occupied by the cleft were made with the use of calibrated photographs. Clefts were divided into 3 types: wide throughout, wide rostrally, and slit throughout. RESULTS: Sneezing was the most frequent clinical sign (43 of 65 over the past month, 34 of 65 when most affected). There was a greater frequency of material lodging in the cleft in the wide-throughout clefts (13 of 16 dogs) compared to the slit-throughout clefts (7 of 19 dogs). Veterinary removal of material was required in 10 of 68 episodes (7 of 31 dogs). There was no correlation between cleft size and prevalence of clinical signs or QoL. Sixty-three percent of dogs had a perfect QoL on a weighted scale, while 83.3% had a perfect score on a visual analog scale. Sixty-four of 65 owners would adopt another dog with a CP. CONCLUSIONS: Measures of QoL were favorable among dogs treated conservatively for CP. CLINICAL RELEVANCE: Conservative management appears to be a viable option for treatment of CPs in some dogs.

Gut Microbiome and Osteoarthritis: Insights From the Naturally Occurring Canine Model of Osteoarthritis.

OBJECTIVE: The purpose of this study was to enhance the current knowledge of the relationship between the gut microbiome and osteoarthritis (OA) and associated pain using pet dogs as a clinically relevant translational model. METHODS: Fecal samples were collected from 93 owned pet dogs. Dogs were designated as either clinically healthy or OA pain using validated methods. Metagenomic profiling was performed through shotgun sequencing using the Illumina NovaSeq platform. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance. Comparisons between healthy and OA-pain groups were performed individually for each taxa using nonparametric tests following Benjamini and Hochberg adjustment for multiple comparisons. Permutation analysis of variance was performed using Bray-Curtis distance matrices. All downstream analyses were completed in R. RESULTS: No significant differences between healthy and OA-pain dogs were observed for alpha and beta diversity. We found 13 taxa with nominally significant (P < 0.05) associations with OA case status, but none of the associations remained significant after adjustment for multiple comparisons. No differences in alpha or beta diversities or the Firmicutes to Bacteroidetes ratio were found regarding pain severity, mobility or activity level, age, or body composition score. CONCLUSION: Similar to recent studies in humans, the present study did not demonstrate a significant difference in the fecal microbial communities between dogs with OA pain and healthy control dogs. Future research in this naturally occurring model should expand on these data and relate the gut microbiome to gut permeability and circulating proinflammatory and anti-inflammatory molecules to better understand the influence of the gut microbiome on OA and OA pain.

Prevalence of radiographic appendicular osteoarthritis and associated clinical signs in young dogs.

This study aimed to determine the prevalence of osteoarthritis (OA) and associated clinical signs in young dogs. Owners of dogs aged 8 months-4 years from a single practice, were contacted in random order, to participate in a general health screen. Clinical and orthopedic examinations were performed. Each joint was scored for pain reactions (0-4). Orthogonal radiographs of all joints were made under sedation. Each joint was scored for radiographic OA (rOA) severity on an 11-point scale. Clinical OA (cOA) was defined as an overlap of rOA and joint pain in ≥ 1 joint. Owners completed OA questionnaires. The owners of 123 dogs agreed to participate. Overall, 39.8% (49/123) of dogs had rOA in ≥ 1 joint, and 16.3% (20/123) or 23.6% (29/123) dogs had cOA, depending on the cut-off value of joint pain; moderate (2), or mild (1), respectively. Owners of dogs with cOA observed signs of impairment in approximately 30% of cases. Only 2 dogs with cOA were receiving OA pain management. The most commonly affected joints in descending order of frequency were elbow, hip, tarsus, and stifle. Radiographically visible OA is common in young dogs, and 40-60% of dogs with rOA had cOA. However, OA-pain appears underdiagnosed and undertreated in young dogs.