@article{stevens_norris_arbeeva_carter_enomoto_nelson_lascelles_2024, title={Gut Microbiome and Osteoarthritis: Insights From the Naturally Occurring Canine Model of Osteoarthritis}, volume={8}, ISSN={["2326-5205"]}, DOI={10.1002/art.42956}, abstractNote={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.}, journal={ARTHRITIS & RHEUMATOLOGY}, author={Stevens, Christina and Norris, Samantha and Arbeeva, Liubov and Carter, Scott and Enomoto, Masataka and Nelson, Amanda E. and Lascelles, B. Duncan X.}, year={2024}, month={Aug} } @article{enomoto_castro_hash_thomson_nakanishi-hester_perry_aker_haupt_opperman_roe_et al._2024, title={Prevalence of radiographic appendicular osteoarthritis and associated clinical signs in young dogs}, volume={14}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-024-52324-9}, abstractNote={AbstractThis 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.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Enomoto, Masataka and Castro, Nicholas and Hash, Jonathan and Thomson, Andrea and Nakanishi-Hester, Aoi and Perry, Erin and Aker, Savannah and Haupt, Emily and Opperman, Logan and Roe, Simon and et al.}, year={2024}, month={Feb} } @article{response to treatment with grapiprant as part of a standard multimodal regimen in young dogs with appendicular joint osteoarthritis associated pain_2024, DOI={10.17615/mwp9-y832}, journal={Frontiers}, year={2024} } @article{enomoto_hash_cole_sanchez_thomson_perry_aker_nakanishi-hester_haupt_opperman_et al._2024, title={Response to treatment with grapiprant as part of a standard multimodal regimen in young dogs with appendicular joint osteoarthritis associated pain}, volume={11}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2024.1461628}, abstractNote={The response to medical management of young dogs with osteoarthritis (OA) associated pain has not been evaluated. Using an open-label design, the effectiveness, over a 4-month period, of standardized management (grapiprant/fish oil/exercise) for treating OA pain in young dogs was evaluated.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Enomoto, Masataka and Hash, Jonathan and Cole, Tracey and Sanchez, Maria D. Porcel and Thomson, Andrea and Perry, Erin and Aker, Savannah and Nakanishi-Hester, Aoi and Haupt, Emily and Opperman, Logan and et al.}, year={2024}, month={Oct} } @article{wu_nichols_foster_martin_dieffenderfer_enomoto_lascelles_russenberger_brenninkmeyer_bozkurt_et al._2023, title={An Exploration of Machine Learning Methods for Gait Analysis of Potential Guide Dogs}, url={https://doi.org/10.1145/3637882.3637883}, DOI={10.1145/3637882.3637883}, abstractNote={Gait analysis is important for guide dog organizations, as ideal guide dogs have a smooth and efficient gait, where they can also easily shift between and maintain various gaits. Gait quality and natural traveling speed are two of the multiple factors important in matching a guide dog to its visually impaired handler. Gait evaluation typically includes subjective visual observation of the dog or objective assessments obtained from special-designed equipment. Guide dog organizations need a method to easily collect and analyze objective data of gait information. In this work, we explored how various machine learning models could learn and analyze gait patterns from inertial measurements data that were collected during two different data collection experiments using a wearable sensor device. We also evaluated how well each machine learning model could generalize behavior patterns from various dogs under different environments. Additionally, we compared how sensor placement locations could affect gait prediction performance by attaching the sensor device to the dog's neck and back area respectively. The tested machine learning models were able to classify different gaits in the range of 42% to 91% in terms of accuracy, and predict various gait parameters with an error rate ranging from 14% to 29% depending on the setup. Furthermore, we also observed that using behavior data collected from the neck region contains more movement information than the back area. By performing a cross-dataset generalization test on the machine learning models, we found that even with performance drop, the models were able to learn gait-specific behavior patterns that are generalizable for different dogs. Although the results were preliminary, the proposed gait analysis exploration still showed promising potential for studying behavior patterns of candidate guide dogs.}, journal={TENTH INTERNATIONAL CONFERENCE ON ANIMAL-COMPUTER INTERACTION, ACI 2023}, author={Wu, Yifan and Nichols, Colt and Foster, Marc and Martin, Devon and Dieffenderfer, James and Enomoto, Masataka and Lascelles, B. Duncan X. and Russenberger, Jane and Brenninkmeyer, Gerald and Bozkurt, Alper and et al.}, year={2023} } @article{nakanishi_lascelles_allen_case_gearing_enomoto_2022, title={A Pilot, Open-Label Study to Evaluate the Efficacy of Intra-Articular Administration of a Caninized TNF Receptor Fc Fusion Protein as a Treatment for Osteoarthritis-Associated Joint Pain}, volume={9}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2022.836709}, abstractNote={Tumor necrosis factor-α (TNF-α) is a potential target for osteoarthritis (OA) treatment. In several recent clinical studies in human OA, anti-TNF-α therapy showed promising results; however, these were open-label and based on patient-reported outcome measures. In this study, we developed a caninized TNF-α receptor-Fc (caTNFR-Fc) fusion protein and conducted a non-randomized, open-label, pilot study in dogs with OA using objectively measured ground reaction forces and activity. The aims of the study were to assess the efficacy of the intra-articular (IA) injection of the caTNFR-Fc fusion protein as a treatment for OA pain, and additionally to evaluate TNF concentrations in synovial fluid (SF) between joints with/without OA in dogs. Dogs (n = 12) with single-limb lameness due to single joint appendicular OA were recruited. All dogs received caTNFR-Fc fusion protein injection into the affected joint under sedation. Objective kinetic gait analysis using force plate was performed prior to (baseline), and at 14- and 28-days following treatment. Additionally, SF samples were collected from OA joints (n = 69) and non-OA joints (n = 79) in a different cohort of dogs and TNF-α were measured using enzyme-linked immunosorbent assay. No significant treatment effects on the limb use, activity, and the questionnaire were found. The concentration of TNF-α was significantly higher in OA joints than in healthy joints (p = 0.0019), but TNF-α was detected in only 10/69 OA samples. The IA injection of caTNFR-Fc fusion protein provided no benefit in terms of objective limb use and activity data in dogs with OA in this pilot study. Although the SF concentration of TNF-α was significantly higher in OA joints, few OA joints had measurable TNF-α. Collectively, the data indicate TNF-α may not be a good therapeutic target in canine OA.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Nakanishi, Aoi and Lascelles, B. Duncan X. and Allen, Julie and Case, Beth and Gearing, David and Enomoto, Masataka}, year={2022}, month={Jun} } @article{ortiz_belda_hash_enomoto_robertson_lascelles_2022, title={Initial exploration of the discriminatory ability of the PetPace collar to detect differences in activity and physiological variables between healthy and osteoarthritic dogs}, volume={3}, ISSN={["2673-561X"]}, url={http://dx.doi.org/10.3389/fpain.2022.949877}, DOI={10.3389/fpain.2022.949877}, abstractNote={BackgroundAccelerometry has been used to evaluate activity in dogs with osteoarthritis (OA) pain, especially in relation to effect of treatment; however no studies have compared accelerometry-measured activity in dogs with OA-pain and healthy dogs. The aims of this study were to (1) compare activity output from the PetPace collar with the validated Actical monitor and (2) determine if PetPace collar outputs (overall activity, activity levels, body position, and vital signs) differed between healthy dogs and dogs with OA-pain.MethodsThis was an observational, non-interventional study in healthy dogs and dogs with OA-pain. All dogs were outfitted with the PetPace collar and the Actical monitor simultaneously for 14 days. Output from these devices was compared (correlations), and output from the PetPace device was used to explore differences between groups across the activity and vital sign outputs (including calculated heart rate variability indices).ResultsThere was moderate correlation between the PetPace collar and Actical monitor output (R2 = 0.56, p < 0.001). Using data generated by the PetPace collar, OA-pain dogs had lower overall activity counts and spent less time standing than healthy dogs. Healthy dogs spent more time at higher activity levels than OA-pain dogs. Certain heart rate variability indices in OA-pain dogs were lower than in healthy dogs.Conclusions and clinical relevanceThe results of this study suggest that the PetPace collar can detect differences between healthy dogs and those with OA-pain, and that OA-pain negatively impacts overall activity levels in dogs, and especially higher intensity activity.}, journal={FRONTIERS IN PAIN RESEARCH}, publisher={Frontiers Media SA}, author={Ortiz, Avery Rowlison and Belda, Beatriz and Hash, Jon and Enomoto, Masataka and Robertson, James and Lascelles, B. Duncan X.}, year={2022}, month={Sep} } @article{wu_holder_foster_williams_enomoto_lascelles_bozkurt_roberts_2022, title={Spatial and Temporal Analytic Pipeline for Evaluation of Potential Guide Dogs Using Location and Behavior Data}, url={https://doi.org/10.1145/3565995.3566033}, DOI={10.1145/3565995.3566033}, abstractNote={Training guide dogs for visually-impaired people is a resource-consuming task for guide dog schools. This task is further complicated by a dearth of capabilities to objectively measure and analyze candidate guide dogs’ temperaments as they are placed with volunteer raisers away from guide dog schools for months during the raising process. In this work, we demonstrate a preliminary data analysis workflow that is able to provide detailed information about candidate guide dogs’ day to day physical exercise levels and gait activities using objective environmental and behavioral data collected from a wearable collar-based Internet of Things device. We trained and tested machine learning models to analyze different gait types including walking, pacing, trotting and mixture of walk and trot. By analyzing data both spatially and temporally, a location and behavior summary for candidate dogs is generated to provide insight for guide dog training experts, so that they can more accurately and comprehensively evaluate the future success of the candidate. The preliminary analysis revealed movement patterns for different location types which reflected the behaviors of candidate guide dogs.}, journal={NINTH INTERNATIONAL CONFERENCE ON ANIMAL-COMPUTER INTERACTION, ACI 2022}, author={Wu, Yifan and Holder, Timothy and Foster, Marc and Williams, Evan and Enomoto, Masataka and Lascelles, B. Duncan X. and Bozkurt, Alper and Roberts, David L.}, year={2022} } @article{estes_enomoto_moutos_carson_toth_eggert_stallrich_willard_veis_little_et al._2021, title={Biological resurfacing in a canine model of hip osteoarthritis}, volume={7}, ISSN={["2375-2548"]}, url={https://doi.org/10.1126/sciadv.abi5918}, DOI={10.1126/sciadv.abi5918}, abstractNote={A 3D woven scaffold seeded with MSCs was used to resurface the canine hip, reducing pain and improving joint function.}, number={38}, journal={SCIENCE ADVANCES}, publisher={American Association for the Advancement of Science (AAAS)}, author={Estes, Bradley T. and Enomoto, Masataka and Moutos, Franklin T. and Carson, Megan A. and Toth, Jeffrey M. and Eggert, Peter and Stallrich, Jonathan and Willard, Vincent P. and Veis, Deborah J. and Little, Dianne and et al.}, year={2021}, month={Sep} } @article{enomoto_baines_roe_marcellin-little_lascelles_2021, title={Defining the rate of, and factors influencing, radiographic progression of osteoarthritis of the canine hip joint}, volume={189}, ISSN={["2042-7670"]}, url={https://doi.org/10.1002/vetr.516}, DOI={10.1002/vetr.516}, abstractNote={AbstractBackgroundThis study aimed to define the rate of progression of radiographic osteoarthritis (OA) of the canine hip joint and to describe factors affecting this progression.MethodsDogs that underwent unilateral total hip replacement (THR) were reviewed for the evaluation of radiographic appearance of the non‐operated hip joint over time. Standard extended ventrodorsal hip radiographs were taken preoperatively and postoperatively. All images were anonymized, randomized and scored using three different methods. The mean daily change between evaluations was calculated in each individual dog, and the effect of sex, age, body weight, open/closed status of the proximal femoral physis, preoperative severity of OA, time after surgery and their interactions, were investigated as potential influencing factors.ResultsAfter reviewing the medical records, 163 dogs (468 images) met the inclusion criteria. Consistent across the three scoring systems, radiographic progression of OA was greater in younger (open physis) and spayed female dogs. A subset of seven patients (4.3%) had a faster progression of OA and was considered outliers. No dog was rated as outlier by all three scoring systems.ConclusionThe rate of progression of radiographically assessed coxofemoral OA varies greatly, but is faster in younger, spayed female dogs. Unusually fast progression occasionally occurs.}, number={10}, journal={VETERINARY RECORD}, publisher={Wiley}, author={Enomoto, Masataka and Baines, Elizabeth A. and Roe, Simon C. and Marcellin-Little, Denis J. and Lascelles, B. Duncan X.}, year={2021}, month={Jun} } @article{enomoto_lascelles_robertson_gruen_2021, title={Refinement of the Feline Musculoskeletal Pain Index (FMPI) and development of the short-form FMPI}, volume={24}, ISSN={["1532-2750"]}, url={https://doi.org/10.1177/1098612X211011984}, DOI={10.1177/1098612X211011984}, abstractNote={Objectives The aim of this study was to investigate the reliability and responsiveness of the Feline Musculoskeletal Pain Index (FMPI) using the collective results of multiple clinical studies and iteratively refine the FMPI for future use. Methods Data were compiled from previously conducted studies involving client-owned cats with degenerative joint disease (DJD) and which used the FMPI. The reliability of the FMPI was assessed using the data from the initial visits of those studies. For the assessment of responsiveness of the FMPI, only placebo-controlled studies that used analgesic treatments were included. Treatment groups from each study were combined and categorized as ‘placebo’ group and ‘analgesic’ group. Then, the mean change from baseline in score of each FMPI item and across all items within and between these groups were assessed. Based on the results of the reliability and responsiveness of the FMPI, stepwise elimination was used to remove the items that were least able to distinguish between the placebo and analgesic groups. Finally, after the stepwise elimination, a proposed new FMPI-short form (FMPI-sf) was constructed and its reliability was reassessed using the data sets described above. Individual and combined data sets of the studies were also used to compare the responsiveness of the original FMPI and the FMPI-sf. Results The data from 180 cats from four studies were included. The original FMPI had a reasonable reliability, but low/no responsiveness. The elimination process of FMPI items refined the responsiveness of the instrument while maintaining its reliability. When the responsiveness was compared between the original FMPI (17 items) and the FMPI-sf (nine items), the treatment effect between groups was always greater when the FMPI-sf was used. Conclusions and relevance The proposed FMPI-sf may be able to better distinguish between placebo and analgesic effects in cats with DJD. }, number={2}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, publisher={SAGE Publications}, author={Enomoto, Masataka and Lascelles, B. Duncan X. and Robertson, James B. and Gruen, Margaret E.}, year={2021}, month={May} } @article{correlation of artemin and gfrα3 with osteoarthritis pain: early evidence from naturally occurring osteoarthritis-associated chronic pain in dogs_2020, url={http://dx.doi.org/10.3389/fnins.2020.00077}, DOI={10.3389/fnins.2020.00077}, abstractNote={Arthritis, including osteoarthritis (OA) and other musculoskeletal-associated pain, is a worldwide problem, however, effective drug options are limited. Several receptors, neurotransmitters, and endogenous mediators have been identified in rodent models, but the relevance of these molecules in disease-associated pain is not always clear. Artemin, a neurotrophic factor, and its receptor, glial-derived neurotrophic factor (GDNF) family receptor alpha-3 (GFRα3), have been identified as involved in pain in rodents. Their role in OA-associated pain is unknown. To explore a possible association, we analyzed tissue from naturally occurring OA in dogs to characterize the correlation with chronic pain. We used behavioral assessment, objective measures of limb use, and molecular tools to identify whether artemin and GFRα3 might be associated with OA pain. Our results using banked tissue from well-phenotyped dogs indicates that artemin/GFRα3 may play an important, and hitherto unrecognized, role in chronic OA-associated pain. Elevated serum levels of artemin from osteoarthritic humans compared to healthy individuals suggest translational relevance. Our data provide compelling evidence that the artemin/GFRα3 signaling pathway may be important in OA pain in both non-humans and humans and may ultimately lead to novel therapeutics.}, journal={Frontiers in Neuroscience}, year={2020}, month={Feb} } @article{enomoto_lascelles_gruen_2020, title={Development of a checklist for the detection of degenerative joint disease-associated pain in cats}, url={https://doi.org/10.1177/1098612X20907424}, DOI={10.1177/1098612X20907424}, abstractNote={Objectives The aim of this study was to develop an evidence-based, clinically expedient checklist to identify cats likely to have degenerative joint disease (DJD)-associated pain. Methods Data were compiled from previously conducted studies that employed a standardized subjective outcome measure consisting of a series of questions. These studies included a prevalence study (with DJD non-informed owners) and therapeutic trials (with DJD-informed owners). For each cat, and each question, response scores were converted to ‘impaired’ and ‘unimpaired’. Cats were categorized as ‘DJD pain’ and ‘non-DJD’ based on orthopedic pain and radiographic DJD scores. These binary data were compared between cat phenotypes (non-DJD and DJD pain) for each question. Sensitivity and specificity of each question were calculated using the binary data; based on this, potential questions for the checklist were selected. Sensitivity and specificity across this group of questions were calculated, and questions sequentially removed to optimize length, sensitivity and specificity. Finally, the proposed checklist was applied to a novel data set to evaluate its ability to identify cats with DJD pain. Results In total, 249 DJD pain cats and 53 non-DJD cats from five studies were included. Nine questions with adequate sensitivity and specificity were initially identified. Following sequential removal of questions, a checklist with six binary questions was proposed. Based on the data from the cohorts of DJD-informed and DJD non-informed owners, the sensitivity and specificity of the proposed checklist were approximately 99% and 100%, and 55% and 97%, respectively. Conclusions and relevance The proposed checklist represents a data-driven approach to construct a screening checklist for DJD pain in cats. This checklist provides a clinically expedient tool likely to increase veterinarians’ ability to screen for DJD pain in cats. The identified behaviors comprising the checklist may further provide a foundation for increasing awareness of DJD pain among cat owners. }, journal={Journal of Feline Medicine and Surgery}, author={Enomoto, Masataka and Lascelles, B Duncan X and Gruen, Margaret E}, year={2020}, month={Dec} } @article{pet dogs with subclinical acute radiodermatitis experience widespread somatosensory sensitization_2019, url={http://dx.doi.org/10.1667/rr15468.1}, DOI={10.1667/rr15468.1}, abstractNote={Radiation-induced dermatitis (RID) is a common and painful complication of radiotherapy. When severe, radiation-associated pain (RAP) can reduce the efficacy of radiotherapy by limiting the radiation dose given, and/or necessitating breaks in treatment. Current RAP mitigation strategies are of limited efficacy. Our long-term goal is to develop a comparative oncology model, in which novel analgesic interventions for RAP can be evaluated. The aim of this study was to validate quantitative end points indicative of RAP in pet dogs with subclinical and low-grade RID. Extremity soft tissue sarcomas were treated with post-operative irradiation (54 Gy in 18 fractions). Visual toxicity scores, questionnaire-based pain instruments and objective algometry [mechanical quantitative sensory testing (mQST)], were evaluated regularly. Breed-matched control populations were also evaluated to address the effect of potential confounders. Skin biopsies from within the irradiated field were collected at baseline and after 24 Gy irradiation, for analysis of pain-related genes using the nanoString nCounter platform. Relative to control populations, mechanical thresholds decreased in irradiated test subjects as the total radiation dose increased, with the most pronounced effect at the irradiated site. This was accompanied by increased mRNA expression of GFRα3, TNFα, TRPV2 and TRPV4. In a separate set of dogs with moderate-to-severe RID, serum concentrations of artemin (the ligand for GFRα3) were elevated relative to controls (P = 0.015). Progressive reduction in mechanical thresholds, both locally and remotely, indicates widespread somatosensory sensitization during radiation treatment. mQST in pet dogs undergoing radiation treatment represents an innovative tool for preclinical evaluation of novel analgesics.}, journal={Radiation Research}, year={2019}, month={Dec} } @article{muller_enomoto_buono_steiner_lascelles_2019, title={Placebo-controlled pilot study of the effects of an eggshell membrane-based supplement on mobility and serum biomarkers in dogs with osteoarthritis}, volume={253}, DOI={10.1016/j.tvjl.2019.105379}, abstractNote={Osteoarthritis (OA) is a debilitating disease in dogs. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat OA; however, many dogs do not obtain adequate pain relief with an NSAID alone. This pilot study evaluated the systemic anti-inflammatory and mobility enhancing effects of an eggshell membrane-based nutritional supplement in dogs with OA-associated pain and mobility impairment. Twenty-seven dogs with OA-associated pain were enrolled into a randomized, double-masked, placebo-controlled, proof of principle pilot study and received either placebo or an eggshell membrane-based nutritional supplement over a 12-week period. Inflammatory biomarkers (IL-2, IL-6, IL-8, tumor necrosis factor-α, C-reactive protein, S100A12, and N-methylhistamine) were measured at Day 0 and Day 84. Owner questionnaires (CBPI and LOAD) were completed at Day 0, Day 42, and Day 84. Differences between groups over time were calculated. Twenty-two dogs completed the pilot study. Inflammatory biomarker IL-2 decreased in the supplement group, compared to the placebo group. Although small, the difference was statistically significant at an alpha of 0.1 (P=0.069). LOAD scores were numerically lower in the supplement group, but not significantly different from the placebo group at Day 0. Day 84 LOAD scores were significantly lower in the supplement group compared to the placebo group (P=0.034). CBPI results did not show the same pattern. The changes in biomarkers and LOAD scores were small, and do not provide definitive evidence of positive effects. However, these pilot results provide a rationale for performing a larger placebo-controlled study of the potential effects of the eggshell membrane-based nutritional supplement.}, journal={The Veterinary Journal}, publisher={Elsevier BV}, author={Muller, C. and Enomoto, M. and Buono, A. and Steiner, J.M. and Lascelles, B.D.X.}, year={2019}, month={Nov}, pages={105379} } @article{enomoto_mantyh_murrell_innes_lascelles_2019, title={Anti-nerve growth factor monoclonal antibodies for the control of pain in dogs and cats}, volume={184}, DOI={10.1136/vr.104590}, abstractNote={Nerve growth factor (NGF) is essential for the survival of sensory and sympathetic neurons during development. However, in the adult, NGF and its interaction with tropomyosin receptor kinase A receptor (TrkA) has been found to play a critical role in nociception and nervous system plasticity in pain conditions. Thus, various monoclonal antibody (mAb) therapies targeting this pathway have been investigated in the development of new pharmacotherapies for chronic pain. Although none of the mAbs against NGF are yet approved for use in humans, they look very promising for the effective control of pain. Recently, species‐specific anti‐NGF mAbs for the management of osteoarthritis (OA)‐associated pain in dogs and cats has been developed, and early clinical trials have been conducted. Anti‐NGF therapy looks to be both very effective and very promising as a novel therapy against chronic pain in dogs and cats. This review outlines the mechanism of action of NGF, the role of NGF in osteoarthritis, research in rodent OA models and the current status of the development of anti‐NGF mAbs in humans. Furthermore, we describe and discuss the recent development of species‐specific anti‐NGF mAbs for the treatment of OA‐associated pain in veterinary medicine.}, number={1}, journal={Vet Rec}, publisher={BMJ}, author={Enomoto, M. and Mantyh, P.W. and Murrell, J. and Innes, J.F. and Lascelles, B.D.X.}, year={2019}, month={Jan}, pages={14} } @article{hunt_goff_jenkins_harris_knowles_lascelles_enomoto_mendl_whay_murrell_et al._2018, title={Electrophysiological characterisation of central sensitisation in canine spontaneous osteoarthritis}, volume={159}, ISSN={["1872-6623"]}, url={https://dx.doi.org/10.1097/j.pain.0000000000001336}, DOI={10.1097/j.pain.0000000000001336}, abstractNote={Abstract In man, central sensitisation (CS) contributes to the pain of osteoarthritis (OA). Dogs with spontaneous OA may also exhibit CS. Electrophysiological reflex measurements are more objective than behavioural assessments and can be used to evaluate CS in preclinical and clinical studies. It was hypothesised that dogs suffering from OA would exhibit electrophysiological characteristics indicative of CS, associated with reduced diffuse noxious inhibitory controls (DNICs). One hundred and seventeen client-owned dogs were recruited to the study. Hind limb nociceptive withdrawal reflex thresholds, stimulus response, and temporal summation characteristics were recorded, during alfaxalone anaesthesia, from 46 OA dogs, 29 OA dogs receiving nonsteroidal anti-inflammatory drugs (OANSAIDs), and 27 breed- and weight-matched control dogs. Efficacy of DNIC was evaluated in 12 control and 11 of the OA dogs, by application of a mechanical conditioning stimulus to the contralateral forelimb. Nociceptive withdrawal reflex thresholds were higher in OA compared with control dogs (P = 0.02). Stimulus response characteristics demonstrated an augmented response in OANSAID dogs compared with OA (P < 0.001) and control (P < 0.001) dogs. Temporal summation demonstrated exaggerated C-fibre-mediated responses in both OA (P < 0.001) and OANSAID (P = 0.005) groups, compared with control animals. Conditioning stimulus application resulted in inhibition of test reflex responses in both OA and control animals (P < 0.001); control animals demonstrated greater inhibition compared with OA (P = 0.0499). These data provide evidence of neurophysiological changes consistent with CS in dogs with spontaneous OA and demonstrate that canine OA is associated with reduced DNIC.}, number={11}, journal={PAIN}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Hunt, James R. and Goff, Megan and Jenkins, Helen and Harris, John and Knowles, Toby G. and Lascelles, B. Duncan X. and Enomoto, Masataka and Mendl, Michael and Whay, Helen R. and Murrell, Joanna C. and et al.}, year={2018}, month={Nov}, pages={2318–2330} } @article{belda_enomoto_case_lascelles_2018, title={Initial evaluation of PetPace activity monitor}, volume={237}, url={https://doi.org/10.1016/j.tvjl.2018.05.011}, DOI={10.1016/j.tvjl.2018.05.011}, abstractNote={Mobility is considered a vital component of health and quality of life in humans and companion animals. Wearable devices for pets that can monitor activity and other aspects of health are increasingly being marketed to veterinarians and owners, with claims around their ability to monitor aspects of health. However, there is little scientific evidence to support the validity of these claims. To address this, the objective of this study was to assess the correlation of the activity measurement from the PetPace device compared to activity output from Actigraph and the validated Actical device. Ten client-owned, healthy dogs were used for the study. The three devices were mounted simultaneously on a dedicated collar and activity was recorded during a period of 7 days. There were moderate correlations between the Actical and the PetPace (r 2 =0.59, P=<0.001). There was high correlation between the PetPace and the Actigraph (r 2 =0.85, P=<0.001) and between the Actical and the Actigraph (r 2 =0.72, P=<0.001). If the Actical activity counts were limited under 50,000 per hour, there was strong correlation between the Actical and the PetPace (r 2 =0.71, P=<0.001) and between the Actical and the Actigraph (r 2 =0.86, P=<0.001). PetPace has a moderate correlation with the most validated activity monitor that has been used in veterinary medicine. Its real-time data acquisition, user friendly interface for owners and cost make this device an attractive tool for monitoring activity in dogs. Further studies maybe needed to evaluate its performance, validity and clinical utility in the field.}, journal={Vet J}, publisher={Elsevier BV}, author={Belda, B. and Enomoto, M. and Case, B.C. and Lascelles, B.D.X.}, year={2018}, month={Jul}, pages={63–68} } @article{muller_enomoto_steiner_lascelles_2018, title={Randomized Pilot Trial of the Effects of an Egg-Shell Membrane-Based Supplement (Movoflextm) on Mobility and Serum Biomarkers of Inflammation in Dogs with Osteoarthritis}, volume={31}, ISSN={0932-0814 2567-6911}, url={http://dx.doi.org/10.1055/S-0038-1668204}, DOI={10.1055/s-0038-1668204}, abstractNote={Introduction: Despite increasing interest in nutritional supplements, evidence of analgesic efficacy is lacking beyond the omega-3 fatty acids. The purpose of this pilot study was to evaluate the mobility enhancing and systemic anti-inflammatory effects of an eggshell membrane-based nutritional supplement (Movoflex) in dogs with osteoarthritis (OA)-associated pain and mobility impairment.}, number={S 02}, journal={Veterinary and Comparative Orthopaedics and Traumatology}, publisher={Georg Thieme Verlag KG}, author={Muller, Carrie and Enomoto, Masataka and Steiner, Joerg and Lascelles, B.}, year={2018}, month={Jul}, pages={A1–A25} } @article{enomoto_lascelles_gerard_2017, title={Defining local nerve blocks for feline distal pelvic limb surgery: a cadaveric study}, volume={19}, ISSN={["1532-2750"]}, url={https://dx.doi.org/10.1177/1098612x17690652}, DOI={10.1177/1098612x17690652}, abstractNote={Objectives Anatomical and methodological detail is lacking regarding local anesthetic peripheral nerve block techniques for distal pelvic limb surgery in cats. The aim of this study was to develop, describe and test nerve block methods based on cadaveric dissections and dye injections. Methods Ten pairs of feline pelvic limbs (n = 20) were dissected and the tibial nerve (T n.), common fibular (peroneal) nerve (CF n., and its two branches, the superficial fibular [peroneal] nerve [SpF n.] and the deep fibular [peroneal] nerve [DpF n.]) and the saphenous nerve (Sa n.) were identified. Based on these dissections, a ‘distal crus block’ (selective blockade of the CF n., T n. and Sa n.) and a ‘distal pes block’ (selective blockade of the SpF n., DpF n., T n. and Sa n.) were developed for surgical procedures in two different regions of the distal pelvic limb. Techniques were tested using new methylene blue (NMB) dye injections in feline pelvic limbs (n = 12). Using a 25 G × 5/8 inch needle and 1 ml syringe, 0.1 ml/kg of NMB dye solution was injected at the site of the CF n., and 0.05 ml/kg was injected at the sites of the SpF n., DpF n., Sa n. and T n. The length and circumference (fully or partially stained) of each stained nerve were measured. Results Positive staining of nerves was observed in 12/12 limbs. The lengths stained for the CF n., DpF n., SpF n., Sa n. and T n. were 27.19 ± 7.13, 20.39 ± 5.57, 22.82 ± 7.13, 30.89 ± 6.99 and 25.16 ± 8.09 mm, respectively. The nerves were fully stained in 12, 12, 10, 11 and 11 out of 12 limbs, respectively. Conclusions and relevance These two, three-point injection methods may be an effective perioperative analgesia technique for feline distal pelvic limb procedures. }, number={12}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, publisher={SAGE Publications}, author={Enomoto, Masataka and Lascelles, B. Duncan X. and Gerard, Mathew P.}, year={2017}, month={Dec}, pages={1215–1223} } @article{enomoto_kigin_bledsoe_slone_hash_smith_lascelles_2017, title={Pilot evaluation of a novel unilateral onychectomy model and efficacy of an extended release buprenorphine product}, volume={13}, journal={BMC Veterinary Research}, author={Enomoto, M. and Kigin, P. D. and Bledsoe, D. and Slone, R. and Hash, J. and Smith, C. E. and Lascelles, B. D. X.}, year={2017} } @article{enomoto_kigin_bledsoe_slone_hash_smith_lascelles_2016, title={Pilot evaluation of a novel unilateral onychectomy model and efficacy of an extended release buprenorphine product}, volume={13}, DOI={10.1186/s12917-017-0943-5}, abstractNote={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.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.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.}, number={1}, journal={BMC Veterinary Research}, publisher={Springer Nature}, author={Enomoto, Masataka and Kigin, Patricia D. and Bledsoe, David and Slone, Robyn and Hash, Jonathan and Smith, Charles E. and Lascelles, B. Duncan X.}, year={2016} } @article{enomoto_lascelles_gerard_2016, title={Defining the local nerve blocks for feline distal thoracic limb surgery: a cadaveric study}, volume={18}, ISSN={["1532-2750"]}, url={https://dx.doi.org/10.1177/1098612x15597967}, DOI={10.1177/1098612x15597967}, abstractNote={Objectives Though controversial, onychectomy remains a commonly performed distal thoracic limb surgical procedure in cats. Peripheral nerve block techniques have been proposed in cats undergoing onychectomy but evidence of efficacy is lacking. Preliminary tests of the described technique using cadavers resulted in incomplete staining of nerves. The aim of this study was to develop nerve block methods based on cadaveric dissections and test these methods with cadaveric dye injections. Methods Ten pairs of feline thoracic limbs (n = 20) were dissected and superficial branches of the radial nerve (RSbr nn.), median nerve (M n.), dorsal branch of ulnar nerve (UDbr n.), superficial branch of palmar branch of ulnar nerve (UPbrS n.) and deep branch of palmar branch of ulnar nerve (UPbrDp n.) were identified. Based on these dissections, a four-point block was developed and tested using dye injections in another six pairs of feline thoracic limbs (n = 12). Using a 25 G × 5/8 inch needle and 1 ml syringe, 0.07 ml/kg methylene blue was injected at the site of the RSbr nn., 0.04 ml/kg at the injection site of the UDbr n., 0.08 ml/kg at the injection site of the M n. and UPbrS n., and 0.01 ml/kg at the injection site of the UPbrDp n. The length and circumference of each nerve that was stained was measured. Results Positive staining of all nerves was observed in 12/12 limbs. The lengths stained for RSbr nn., M n., UDbr n., UPbrS n. and UPbrDp n. were 34.9 ± 5.3, 26.4 ± 4.8, 29.2 ± 4.0, 39.1 ± 4.3 and 17.5 ± 3.3 mm, respectively. The nerve circumferences stained were 93.8 ± 15.5, 95.8 ± 9.7, 100 ± 0.0, 100 ± 0.0 and 93.8 ± 15.5%, respectively. Conclusions and relevance This described four-point injection method may be an effective perioperative analgesia technique for feline distal thoracic limb procedures. }, number={10}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, publisher={SAGE Publications}, author={Enomoto, Masataka and Lascelles, B. Duncan X. and Gerard, Mathew P.}, year={2016}, month={Oct}, pages={838–845} }