Surveillance of Ancylostoma caninum in naturally infected dogs in Quebec, Canada, and assessment of benzimidazole anthelmintics reveal a variable efficacy with the presence of a resistant isolate in imported dogs.

Ancylostoma caninum is a widely prevalent parasitic nematode in dogs across the world. There has been a notable increase in reports of anthelmintic resistance in A. caninum within the United States of America in recent years, which has led us to investigate the potential of this scenario in Canada. The study objectives were to assess the prevalence of A. caninum in two different groups, including a colony of rescued dogs in Canada and three imported Greyhound dogs from USA, and to evaluate the efficacy of two benzimidazole (BZ) anthelmintics against A. caninum, complemented with a molecular genetic analysis adapted to low prevalence. Fecal samples were collected at pre- and post-treatment with fenbendazole for the native shelters-origin group, and a combination of anthelmintic formulations, including the pro-BZ febantel for the USA-origin group. The coprology analyses found several genera of internal parasites. Canine ancylostomiasis was the most prevalent parasitosis with 30.77% in the native group and 100% in the USA group, but with overall low average of A. caninum eggs per gram. Through the fecal egg count reduction test (FECRT), applying a cut-off at 90% as baseline of egg reduction for successful efficacy, BZ showed variable efficacy. Furthermore, molecular analysis confirmed the presence of A. caninum in both groups of dogs and found differences in the genetics linked to BZ resistance on the A. caninum ß-tubulin isotype 1 gene. In the isolate from the native group, both codons 167 and 200 were homozygous without the presence of single nucleotide polymorphism (SNP). In contrast, the selected isolate from the USA group, showed a homozygous allele at position 200 and a heterozygous SNP at position 167. The latter was congruent with the low efficacy in FECRT and agrees with the recent findings of USA A. caninum isolate resistant phenotype to the BZ anthelmintics. The limitations of the study include an overall low eggs-per-gram in both canine groups, and the shortage of additional fecal samples from the USA group, restraining the molecular analysis only to one out of the three Greyhounds. This study provided some insights on the efficacy of BZs against A. caninum and revealed the presence of BZ resistant isolates in imported dogs in Quebec, Canada. All this information should be considered, for choosing the best strategy in the control of A. caninum using anthelmintic drugs.

Concurrent Validation of MI-CAT(V), a Clinical Metrology Instrument for Veterinarians Assessing Osteoarthritis Pain in Cats, through Testing for Firocoxib Analgesic Efficacy in a Prospective, Randomized, Controlled, and Blinded Study.

Veterinarians face the lack of a rapid, reliable, inexpensive, and treatment-sensitive metrological instrument reflecting feline osteoarthritis (OA) pain. The Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians (MI-CAT(V)) has been refined in 4 sub-sections, and we proposed its concurrent validation. Cats naturally affected by OA (n = 32) were randomly distributed into 4 groups of firocoxib analgesic (Gr. A: 0.40; B: 0.25; C: 0.15, and P: 0.00 mg/kg bodyweight). They were assessed during Baseline, Treatment, and Recovery periods using MI-CAT(V) and objective outcomes (effort path, stairs assay compliance, and actimetry). The MI-CAT(V) total score correlated to the effort path and actimetry (RhoS = -0.501 to -0.453; p < 0.001), also being sensitive to treatment responsiveness. The pooled treatment group improved its total, gait, and body posture scores during Treatment compared to the Baseline, Recovery, and placebo group (p < 0.05). The MI-CAT(V) suggested a dose-(especially for Gr. B) and cluster-response. Cats in the moderate and severe MI-CAT(V) clusters responded to firocoxib with a remaining analgesic effect, while the mild cluster seemed less responsive and experienced a negative rebound effect. The MI-CAT(V) was validated for its OA pain severity discriminatory abilities and sensitivity to firocoxib treatment, providing a new perspective for individualized care.

Comparison of intradermal and serum testing for environmental allergen-specific immunoglobulin E determination in a laboratory colony of cats with naturally acquired atopic syndrome.

BACKGROUND: Allergen testing is used to select antigens included in the desensitisation vaccine. Intradermal skin test (IDT) is the gold standard in cats, yet allergen-specific immunoglobulin (Ig)E serological testing (ASIS) is often used. Feline data are lacking regarding the agreement between IDT and ASIS results. HYPOTHESIS/OBJECTIVES: The first objective of the study was to establish a colony of cats with naturally acquired feline atopic syndrome (FAS). Further objectives were to define their hypersensitivity disorder to detail the allergen tests results, and to assess similarity between the allergen tests. ANIMALS: Thirty-five cats with FAS and 10 control cats. MATERIALS AND METHODS: Enrolled cats went through a five phase-screening and quarantine process before joining the colony. An elimination diet trial was performed on all FAS cats. ASIS and IDT were consecutively performed on all cats under sedation. RESULTS: Reactions to 34 allergens were compiled for the 45 cats. Global sensitivity and specificity of ASIS were 34.7% and 78.9%, respectively. Only flea (ICC = 0.26, p = 0.040) and Dermatophagoides pteronyssinus (ICC = 0.48, p < 0.001) allergens had a significant intraclass correlation (weak agreement). Two FAS cats had negative tests including one cat with a concomitant food allergy. CONCLUSIONS AND CLINICAL RELEVANCE: This study depicts the first reported colony of cats with naturally acquired FAS. This is the first feline study to compare and show the poor agreement between allergen tests with a panel of 34 allergens. This colony also harbours two cats with FAS with negative allergen tests. These may represent the first described cats with an intrinsic form of atopic syndrome.

Development of Two Innovative Performance-Based Objective Measures in Feline Osteoarthritis: Their Reliability and Responsiveness to Firocoxib Analgesic Treatment.

The metrological properties of two performance-based outcome measures of feline osteoarthritis (OA), namely Effort Path (Path) and Stairs Assay Compliance (Stairs), were tested. Cats naturally affected by OA (n = 32) were randomly distributed into four groups (A: 0.40, B: 0.25, C: 0.15, or D: 0.00 mg firocoxib/kg bodyweight) and assessed during baseline, treatment, and recovery periods. For Path, from an elevated walking platform, the cats landed on a pressure-sensitive mattress and jumped up onto a second elevated platform. Analysis included velocity, time to completion, peak vertical force (PVF), and vertical impulse. For Stairs, the number of steps and time to completion were recorded for 16 steps up and down in a 4 min period. Reliability was moderate to very good for Path and poor to good for Stairs. Different normalization methods are described in the manuscript. The placebo group remained stable within-time in Path, whereas treated cats trotted faster on the ramp (p < 0.0001), improved their PVF (p < 0.018) and completed the task quicker (p = 0.003). The percentage of cats completing the Stairs finish line was higher under treatment (p < 0.036), with huge effect size, the placebo group results being stable within-time. Both are promising performance-based outcome measures to better diagnose and manage feline OA pain.

A 2022 Systematic Review and Meta-Analysis of Enriched Therapeutic Diets and Nutraceuticals in Canine and Feline Osteoarthritis.

With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.

Estrogenic impregnation alters pain expression: analysis through functional neuropeptidomics in a surgical rat model of osteoarthritis.

PURPOSE: Several observational studies suggest that estrogens could bias pain perception. To evaluate the influence of estrogenic impregnation on pain expression, a prospective, randomized, controlled, blinded study was conducted in a Sprague-Dawley rat model of surgically induced osteoarthritis (OA). METHODS: Female rats were ovariectomized and pre-emptive 17ß-estradiol (0.025 mg, 90-day release time) or placebo pellets were installed subcutaneously during the OVX procedures. Thirty-five days after, OA was surgically induced on both 17ß-estradiol (OA-E) and placebo (OA-P) groups. Mechanical hypersensitivity was assessed by static weight-bearing (SWB) and paw withdrawal threshold (PWT) tests. Mass spectrometry coupled with high-performance liquid chromatography (HPLC-MS) was performed to quantify the spinal pronociceptive neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), bradykinin (BK), somatostatin (SST), and dynorphin-A (Dyn-A). RESULTS: Compared to control, ovariectomized rats presented higher SP (P = 0.009) and CGRP (P = 0.017) concentrations. OA induction increased the spinal level of SP (+ 33%, P < 0.020) and decreased the release of BK (- 20%, (P < 0.037)). The OA-E rats at functional assessment put more % body weight on the affected hind limb than OA-P rats at D7 (P = 0.027) and D56 (P = 0.033), and showed higher PWT at D56 (P = 0.009), suggesting an analgesic and anti-allodynic effect of 17ß-estradiol. Interestingly, the 17ß-estradiol treatment counteracted the increase of spinal concentration of Dyn-A (P < 0.016) and CGRP (P < 0.018). CONCLUSION: These results clearly indicate that 17ß-estradiol interfers with the development of central sensitization and confirm that gender dimorphism should be considered when looking at pain evaluation.

Using Ambient Assisted Living to Monitor Older Adults With Alzheimer Disease: Single-Case Study to Validate the Monitoring Report.

BACKGROUND: Many older adults choose to live independently in their homes for as long as possible, despite psychosocial and medical conditions that compromise their independence in daily living and safety. Faced with unprecedented challenges in allocating resources, home care administrators are increasingly open to using monitoring technologies known as ambient assisted living (AAL) to better support care recipients. To be effective, these technologies should be able to report clinically relevant changes to support decision making at an individual level. OBJECTIVE: The aim of this study is to examine the concurrent validity of AAL monitoring reports and information gathered by care professionals using triangulation. METHODS: This longitudinal single-case study spans over 490 days of monitoring a 90-year-old woman with Alzheimer disease receiving support from local health care services. A clinical nurse in charge of her health and social care was interviewed 3 times during the project. Linear mixed models for repeated measures were used to analyze each daily activity (ie, sleep, outing activities, periods of low mobility, cooking-related activities, hygiene-related activities). Significant changes observed in data from monitoring reports were compared with information gathered by the care professional to explore concurrent validity. RESULTS: Over time, the monitoring reports showed evolving trends in the care recipient's daily activities. Significant activity changes occurred over time regarding sleep, outings, cooking, mobility, and hygiene-related activities. Although the nurse observed some trends, the monitoring reports highlighted information that the nurse had not yet identified. Most trends detected in the monitoring reports were consistent with the clinical information gathered by the nurse. In addition, the AAL system detected changes in daily trends following an intervention specific to meal preparation. CONCLUSIONS: Overall, trends identified by AAL monitoring are consistent with clinical reports. They help answer the nurse's questions and help the nurse develop interventions to maintain the care recipient at home. These findings suggest the vast potential of AAL technologies to support health care services and aging in place by providing valid and clinically relevant information over time regarding activities of daily living. Such data are essential when other sources yield incomplete information for decision making.

Early clinical management of severe burn patients using telemedicine: a pilot study protocol.

BACKGROUND: Emergency physicians are responsible for assessing the severity of a patient's burns, which determines whether the patient needs to be transferred to a burn center. Such a proper assessment represents a daunting task because severe burn injuries are rare. Inaccurate estimates often result in unjustified and costly transfers and unneeded fluid resuscitation and assisted ventilation procedures. Telemedicine offers a solution to these challenges. The present pilot study aims to investigate the feasibility, acceptability, and potential value of a large telemedicine initiative at the University of Montreal Health Center's burn center and its network of referring hospitals. METHODS: A three-stage study protocol is proposed to achieve this objective. First, a proof of concept phase will assess the technical feasibility of telemedicine at one referring hospital with a high volume of patient transfers. Second, the organizational and human feasibility of the project will be evaluated in four referring medical centers. All teleconsultation sessions will be analyzed using the WHO's telemedicine implementation model. The third phase will consist of evaluating the potential impacts of telemedicine in a subset of 10 referring hospitals. The quality of communications between referring physicians and specialists will be assessed using semi-structured interviews. A pre-test/post-test with a comparison group design will be used to assess the effects of telemedicine on patient transfers, ventilation procedures, patient complications, mortality, length of ICU stay, and additional surgical procedures. The economic viability of telemedicine will be assessed using a cost-minimization approach. DISCUSSION: The telemedicine initiative is expected to yield positive and significant outcomes that are relevant to a wide range of medical centers that already use or are considering using a similar technology. The contribution of this pilot study lies in its ability to reveal technological, organizational, and human barriers and provide a preliminary assessment of the clinical and economic value of a large-scale telemedicine initiative in the context of burn medicine.

Sensitivity of functional targeted neuropeptide evaluation in testing pregabalin analgesic efficacy in a rat model of osteoarthritis pain.

The monosodium iodoacetate (MIA)-induced joint degeneration in rats is the most used animal model to screen analgesic drugs to alleviate osteoarthritis (OA) pain. This study aimed to evaluate the analgesic efficacy of pregabalin (PGB) in an MIA-induced OA model in rodents by using functional and neuroproteomic pain assessment methods. Treatment group included PGB in curative intent over 9 days compared to gold standard therapy (positive controls) and placebo (negative control). Functional assessments of pain (quantitative sensory testing and operant test) were performed concomitantly with spinal neuropeptides quantification. At day 21 post-OA induction, PGB in MIA rats reduced tactile allodynia (P = 0.028) and improved the place escape/avoidance behaviour (P = 0.04) compared to values recorded at last time-point before initiating analgesic therapy. All spinal neuropeptide concentrations, such as substance P, calcitonin gene-related peptide, bradykinin and somatostatin, came back to normal (non-affected) rat values, compared to their increase observed in MIA rats receiving the placebo (P < 0.0001). Initiated 13 days after chemical OA induction, repeated medication with PGB provided analgesia according to quantitative sensory testing, operant test and targeted neuropeptides pain assessment methods. This report highlights the interest of using reliable and sensitive methods like targeted neuropeptide quantification to detect the analgesic effects of a test article with concomitant functional assessments of pain when studying OA pain components.

Pain characterization and response to palliative care in dogs with naturally-occurring appendicular osteosarcoma: An open label clinical trial.

This study aimed to characterize bone cancer pain (quantitative sensory testing (QST), stance asymmetry index, actimetry, scores of pain and quality of life (QoL)) in dogs with appendicular osteosarcoma (OSA), and to evaluate a stepwise palliative analgesic treatment. The pain profile of thirteen client-owned dogs with OSA was compared with seven healthy dogs. Dogs with OSA were then enrolled in a prospective, open-label, clinical trial. Outcome measures included: primary and secondary mechanical thresholds (MT), conditioned pain modulation (CPM), stance asymmetry index, actimetry (most and least active periods), visual analog scales and QoL. After baseline assessments, stepwise treatment comprised orally administered cimicoxib (2 mg/kg q 24h), amitriptyline (1-1.5 mg/kg q 24h) and gabapentin (10 mg/kg q 8h); re-evaluations were performed after 14 (D14), 21 (D21) and 28 (D28) days, respectively. Statistics used mixed linear models (α = 5%; one-sided). Centralized nociceptive sensitivity (primary and secondary MT, and dynamic allodynia) was recorded in OSA dogs. Healthy dogs had responsive CPM, but CPM was deficient in OSA dogs. Construct validity was observed for the QST protocol. Asymmetry index was significantly present in OSA dogs. The CPM improved significantly at D14. When compared with baseline (log mean ± SD: 4.1 ± 0.04), most active actimetry significantly improved at D14 (4.3 ± 0.04), D21 and D28 (4.2 ± 0.04 for both). When compared with baseline, least active actimetry significantly decreased after treatment at all time-points indicating improvement in night-time restlessness. No other significant treatment effect was observed. Except for tactile threshold and actimetry, all outcomes worsened when gabapentin was added to cimicoxib-amitriptyline. Dogs with bone cancer are affected by widespread somatosensory sensitivity characterized by peripheral and central sensitization and have a deficient inhibitory system. This severe pain is mostly refractory to palliative analgesic treatment, and the latter was only detected by specific and sensitive outcomes.

Peak vertical force in a stabilized canine cranial cruciate deficient stifle model: A one-year follow-up.

This study aimed to describe the peak vertical force (PVF) over a 1-year period in a stabilized canine cranial cruciate deficient stifle model. Our hypothesis was that PVF would be restored to Baseline (intact) at the end of the follow-up. Fifteen (> 20 kg) mixed-breed dogs were included in this study. Cranial cruciate ligament was transected on Day (D) 0 followed by lateral suture stabilization at D28. Peak vertical force was acquired at D-1, D14, D26, D91, D210 and D357. When compared to Baseline, the PVF was significantly decreased at D14, D26, and D91. Values at D210 and D357 were not statistically different to Baseline. This study suggests a return to normal baseline peak vertical force in a canine cranial cruciate deficient stifle model when lateral suture stabilization has been performed 28 days after surgical transection.

Le but de cette étude était de rapporter, chez un modèle canin stabilisé suite à une déficience du genou induite par section transversale du ligament croisé crânial (LCC), l'évolution du pic de force vertical (PFV) sur une année. Notre hypothèse était que le PFV serait normalisé à la fin de la période de suivi.Quinze (> 20 kg) chiens croisés ont été inclus dans l'étude. L'instabilité du genou a été induite par section transversale du ligament croisé crânial au Jour (J) 0, suivie par la stabilisation par suture latérale à J28. Le PFV a été acquis à J−1, J14, J26, J91, J210, et J357.Lorsque comparé à J0, le PFV était significativement diminué à J14, J26 et J91. Les valeurs du PFV à J210 et J357 n'étaient pas différentes qu'à J0.Cette étude suggère le retour des valeurs normales du pic de force verticale chez un modèle d'instabilité induite du genou lorsque la stabilisation a été réalisée 28 jours après la section transversale du ligament croisé crânial.(Traduit par les auteurs).

Refinement of the Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians: detection of naturally occurring osteoarthritis in laboratory cats.

Objectives Feline osteoarthritis causes pain and disability. Detection and measurement is challenging, relying heavily on owner report. This study describes refinement of the Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians. Methods A video analysis of osteoarthritic (n = 6) and non-osteoarthritic (n = 4) cats facilitated expansion of scale items. Three successive therapeutic trials (using gabapentin, tramadol and oral transmucosal meloxicam spray) in laboratory cats with and without natural osteoarthritis (n = 12-20) permitted construct validation (assessments of disease status sensitivity and therapeutic responsiveness) and further scale refinements based on performance. Results Scale osteoarthritic sensitivity improved from phase I to phase III; phase III scale total score ( P = 0.0001) and 4/5 subcategories - body posture ( P = 0.0006), gait ( P = 0.0031), jumping (0.0824) and global distance examination ( P = 0.0001) - detected osteoarthritic cats. Total score inter-rater (intra-class correlation coefficients [ICC] = 0.64-0.75), intra-rater (ICC = 0.90-0.91) and overall internal consistency (Cronbach's alpha = 0.85) reliability were good to excellent. von Frey anesthesiometer-induced paw withdrawal threshold increased with gabapentin in phase I, in osteoarthritic cats ( P <0.001) but not in non-osteoarthritic cats ( P = 0.075). Night-time activity increased during gabapentin treatment. Objective measures also detected tramadol and/or meloxicam treatment effects in osteoarthritic cats in phases II and III. There was some treatment responsiveness: in phase I, 3/10 subcategory scores improved ( P <0.09) in treated osteoarthritic cats; in phase II, 3/8 subcategories improved; and in phase III, 1/5 subcategories improved ( P <0.096). Conclusions and relevance The revised scale detected naturally occurring osteoarthritis, but not treatment effects, in laboratory cats, suggesting future potential for screening of at-risk cats. Further study is needed to confirm reliability, validity (disease sensitivity and treatment responsiveness) and clinical feasibility, as well as cut-off scores for osteoarthritic vs non-osteoarthritic status, in client-owned cats.

Capsular Biofilm Formation at the Interface of Textured Expanders and Human Acellular Dermal Matrix: A Comparative Scanning Electron Microscopy Study.

BACKGROUND: Despite benefits in reducing capsular contractures, textured implants have been associated with significant pitfalls, such a propensity for biofilm formation. Few studies have investigated whether the use of acellular dermal matrix on textured implants produces similar findings. This study aims to characterize biofilm formation at the capsular-acellular dermal matrix interface with scanning electron microscopy. METHODS: The authors performed a prospective observational pilot study in patients undergoing two-stage expander-to-permanent implant exchange. Patients were inflated with Biocell or Siltex expanders, and specimens from the capsular-pectoralis interface and capsular-acellular dermal matrix interface were obtained and examined under scanning electron microscopy for capsular ingrowth and biofilm formation using the Van Herdeen Biofilm Grading System and the Biofilm Thickness Grading Scale. RESULTS: Nine patients including 14 breasts (28 capsular samples in total) were examined. Thick biofilm formation was observed in all specimens from the capsular-acellular dermal matrix interface with Biocell and 25 percent of capsule-pectoralis interface, whereas no biofilm formation was found in Siltex implants. For Biocell implants, a significant difference in biofilm coverage between the upper and lower poles was observed using the Van Herdeen Biofilm Grading System (p = 0.0028) and the Biofilm Thickness Grading Scale (p = 0.0161). CONCLUSIONS: Biocell implants produce a significant rate of biofilm formation over acellular dermal matrix-covered capsules, which is not present in the muscular region or in Siltex implants. Further randomized controlled trials will further elucidate the clinical impact of using acellular dermal matrices with macrotextured implants. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Therapeutic response analysis in dogs with naturally occurring osteoarthritis.

OBJECTIVE: Reporting the rate of positive (+) and negative (-) responders based on an objective outcome measure of pain-related functional disability/lameness in dogs with naturally occurring osteoarthritis (OA), and the relationship between initial lameness severity and the odds of being a (+) responder. STUDY DESIGN: Retrospective analysis of published peer-reviewed clinical trials in dogs with naturally occurring OA. ANIMALS: Dogs (n = 213) with hip and/or stifle afflicted-joints. METHODS: A responder analysis was undertaken using a previously determined cut-off value of ±2.0% of body weight using the peak of vertical force (PVF). Among the selected trials, PVF was acquired under similar conditions. Therapeutic approaches were therapeutic diets, natural health products and nonsteroidal anti-inflammatory drugs. RESULTS: Among dogs receiving a therapeutic approach as described above (n = 121), 62.8% [95% confidence interval, 53.9-70.9] were defined as (+) responders, whereas 11.6% [7.0-18.5] were (-) responders, accounting for a net (+) response rate by 51.2% [42.0-60.4]. In dogs receiving a negative control (n = 92), the net (+) response rate was 1.1% [0.0-5.9]. The number needed to treat was 4, and the effect size 0.7 [0.4-1.0]. The odds ratio of being a (+) responder under the therapeutic approaches was 2.85 [1.57-5.17] (p < 0.001). For every less severe lameness manifested with an increment in PVF by 1% body weight, the chance of being a (+) responder following treatment decreased by 9% (odds ratio 0.91 [0.86-0.97], p = 0.006). CONCLUSION AND CLINICAL RELEVANCE: The rate of (+) responder optimizes decision making for the management of pain-related clinical signs of OA. Evidence-based medicine was further supported by clinical metrics based on an objective outcome measure of pain-related functional disability/lameness. This study also revealed that dogs with a mild lameness are less prone to be improved, emphasizing the need to carefully manage OA dogs in spite of a more subtle affliction.

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.

Spinal neuropeptide modulation, functional assessment and cartilage lesions in a monosodium iodoacetate rat model of osteoarthritis.

BACKGROUND AND AIMS: Characterising the temporal evolution of changes observed in pain functional assessment, spinal neuropeptides and cartilage lesions of the joint after chemical osteoarthritis (OA) induction in rats. METHODS AND RESULTS: On day (D) 0, OA was induced by an IA injection of monosodium iodoacetate (MIA). Rats receiving 2mg MIA were temporally assessed at D3, D7, D14 and D21 for the total spinal cord concentration of substance P (SP), calcitonin gene related-peptide (CGRP), bradykinin (BK) and somatostatin (STT), and for severity of cartilage lesions. At D21, the same outcomes were compared with the IA 1mg MIA, IA 2mg MIA associated with punctual IA injection of lidocaine at D7, D14 and D21, sham (sterile saline) and naïve groups. Tactile allodynia was sequentially assessed using a von Frey anaesthesiometer. Non-parametric and mixed models were applied for statistical analysis. Tactile allodynia developed in the 2mg MIA group as soon as D3 and was maintained up to D21. Punctual IA treatment with lidocaine counteracted it at D7 and D14. Compared to naïve, [STT], [BK] and [CGRP] reached a maximum as early as D7, which plateaued up to D21. For [SP], the increase was delayed up to D14 and maintained at D21. No difference in levels of neuropeptides was observed between MIA doses, except for higher [STT] in the 2mg MIA group (P=0.029). Neuropeptides SP and BK were responsive to lidocaine treatment. The increase in severity of cartilage lesions was significant only in the 2mg MIA groups (P=0.01). CONCLUSION: In the MIA OA pain model, neuropeptide modulation appears early, and confirms the central nervous system to be an attractive target for OA pain quantification. The relationship of neuropeptide release with severity of cartilage lesions and functional assessment are promising and need further validation.

Comparison of lidocaine and lidocaine-epinephrine for the paravertebral brachial plexus block in dogs.

OBJECTIVE: To compare the motor and sensory block efficacy and duration of a modified paravertebral brachial plexus block (PBPB) after administration of lidocaine alone (LI) or combined with epinephrine (LE). STUDY DESIGN: Prospective, randomized, blinded, crossover study. ANIMALS: A total of eight healthy female Beagle dogs. METHODS: Under general anesthesia, modified PBPB was performed on the left thoracic limb using neurostimulation and/or ultrasound guidance to administer lidocaine (2 mg kg-1; 0.2 mL kg-1) either alone (treatment LI, n = 10) or with epinephrine (1:100,000; treatment LE, n = 9). Sensory block was evaluated through reaction to a painful mechanical stimulus applied at five sites on the limb. Motor block effect was evaluated according to visual gait assessments and thoracic limb vertical force measurements under dynamic and static conditions. Data were analyzed using repeated-measures generalized estimating equations. All statistical tests were performed two-sided at the α = 0.05 significance threshold. RESULTS: The duration of sensory block did not differ significantly between treatments. Visible gait impairment was more persistent in LE than in LI (118 ± 63 minutes for LI and 163 ± 23 minutes for LE; mean ± standard deviation) (p = 0.027). At nadir value, dynamic peak vertical force was lower in LE than in LI (p = 0.007). For both dynamic and static evaluations, the nadir and the return to baseline force were delayed in LE (return to normal at 180-200 minutes) when compared with LI (130-140 minutes) (p < 0.005). CONCLUSIONS AND CLINICAL RELEVANCE: The addition of epinephrine to lidocaine prolonged the duration and increased the intensity of the regional block, as verified by visual gait assessment and kinetic analysis. No significant difference was noted between treatments regarding sensory blockade. Kinetic analysis could be useful to evaluate regional anesthetic effect in dogs.

Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis.

OBJECTIVES: This study aimed to (1) compare outcome assessments in normal and osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled, crossover design. METHODS: Twenty cats were included after clinical examination, blood work and full body radiographs were performed. In Phase 1, outcome assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg) orally for 19 days, with a 3-month washout period between treatments. Evaluations were performed in normal and OA cats at baseline and consisted of: 1) peak vertical force (PVF) after staircase exercise; 2) telemetered night-time motor activity (NMA); and 3) response to mechanical temporal summation (RMTS). After treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were analysed with mixed model methods with an alpha-threshold of 5%. RESULTS: Phase 1: 1) PVF (% of body weight; mean ± SD) was higher in normal (59 ± 10.5) than in OA cats (50.6 ± 5.7) (p = 0.005); 2) NMA (no unit) was not different between groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5 (23.5-30)] than in OA cats [14 (8.5-28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively). No clinically important adverse-effects were observed. CONCLUSION: Outcome assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS) are discriminant of OA status. Mobility measured by NMA was not discriminant of OA status, however it increased in OA cats with tramadol treatment. Nociceptive hypersensitivity quantified by RMTS was evident in OA cats and was responsive to tramadol treatment.

Analgesic efficacy of an oral transmucosal spray formulation of meloxicam alone or in combination with tramadol in cats with naturally occurring osteoarthritis.

OBJECTIVE: To evaluate the analgesic efficacy of meloxicam oral transmucosal spray (OTMS) alone and with tramadol in cats with osteoarthritis (OA). STUDY DESIGN: Randomized, blinded study. ANIMALS: Fifteen geriatric cats weighing 4.5 ± 1.0 kg. METHODS: Healthy cats with OA were randomly administered a placebo (every 12 hours orally) and meloxicam OTMS (approximately 0.05 mg kg-1 every 24 hours) (group M, n = 7), or tramadol (3 mg kg-1 every 12 hours orally) and meloxicam OTMS (group TM, n = 8) for 25 days. Evaluations performed before treatment (D0) and at week 3 (W3) consisted of peak vertical force, motor activity and response to mechanical temporal summation of pain (RMTS). Data were analyzed with mixed models and Fisher's exact test. RESULTS: Mean ± standard deviation peak vertical force (percentage of body weight) increased significantly in both groups (p = 0.02), from 47.7 ± 6.5% to 60.5 ± 9.4% in group M, and from 51.8 ± 5.0% to 64.1 ± 6.5% in group TM, with no difference between groups. Motor activity increased in M (from 43 ± 12 to 56 ± 13; p = 0.02), but not in TM. The number of stimulations from RMTS increased in TM only. Cut-off values were reached in a larger number of cats (n = 5) in TM than M (n = 1) (p < 0.05). Gastrointestinal adverse effects were self-limiting in six cats, including five in TM. CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam OTMS had similar effects on peak vertical force, motor activity and pain sensitization as previously reported for oral meloxicam in OA cats. The tramadol-meloxicam combination provided no evident benefit over meloxicam alone, except for central hypersensitivity (assessed with RMTS). Further assessment of the potential toxicity of the combination is required prior to clinical use. Gingival administration was well accepted overall.

Preliminary Validation and Reliability Testing of the Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians, in a Colony of Laboratory Cats.

Subtle signs and conflicting physical and radiographic findings make feline osteoarthritis (OA) challenging to diagnose. A physical examination-based assessment was developed, consisting of eight items: Interaction, Exploration, Posture, Gait, Body Condition, Coat and Claws, (joint) Palpation-Findings, and Palpation-Cat Reaction. Content (experts) and face (veterinary students) validity were excellent. Construct validity, internal consistency, and intra- and inter-rater reliability were assessed via a pilot and main study, using laboratory-housed cats with and without OA. Gait distinguished OA status in the pilot ( p = 0.05) study. In the main study, no scale item achieved statistically significant OA detection. Forelimb peak vertical ground reaction force (PVF) correlated inversely with Gait (Rho s = -0.38 ( p = 0.03) to -0.41 ( p = 0.02)). Body Posture correlated with Gait, and inversely with forelimb PVF at two of three time points (Rho s = -0.38 ( p = 0.03) to -0.43 ( p = 0.01)). Palpation (Findings, Cat Reaction) did not distinguish OA from non-OA cats. Palpation-Cat Reaction (Forelimbs) correlated inversely with forelimb PVF at two time points (Rho s = -0.41 ( p = 0.02) to -0.41 ( p = 0.01)), but scores were highly variable, and poorly reliable. Gait and Posture require improved sensitivity, and Palpation should be interpreted cautiously, in diagnosing feline OA.