Margaret E Gruen

• DVM, MVPH, DACVB
• PhD Student at North Carolina State University

Cortisol is widely used in mammals as a measure of HPA axis response. To estimate response to an acute stressor, minimize pain and ease sample collection, salivary cortisol has become preferred over serum cortisol across a variety of species. This includes domestic dogs in which research with laboratory dogs initially demonstrated the predicted rel...

Background Accelerometry can be used to measure physical activity and is a validated objective measure for evaluating the impact of osteoarthritis (OA) pain in companion animals. However, several factors other than OA pain can affect physical activity in dogs, and relatively little is understood about their influence. Functional linear modeling (FL...

Introduction Human frailty has long been studied and dozens of “frailty scales” have been developed, but equivalent research is more limited in cats. This pilot study aimed to determine the feasibility of recruiting and retaining veterinary practices and owners, collecting study data, and analyzing results about frailty in older cats. Methods Part...

Cognitive test batteries suggest that adult dogs have different types of cognitive abilities that vary independently. In the current study, we tested puppies repeatedly over a crucial period of development to explore the timing and rate at which these different cognitive skills develop. Service dog puppies (n = 113), raised using two different soci...

Introduction Frailty is a well-defined clinical syndrome in humans caused by accumulation of impairments which result in loss of reserve capacity and increased vulnerability to disability, dependence, and death. Dogs are of particular interest in studies of frailty due to the similarities they share with people in their environment, lifestyles, and...

Advancements in veterinary medicine have resulted in increased life spans for dogs, necessitating a better understanding of quality of life for older dogs. This study aimed to evaluate quality of life (QoL) progression and its potential association with mortality in senior and geriatric dogs. The Canine Owner-Reported Quality of Life Questionnaire...

Presbycusis, or age-related hearing loss, affects both elderly humans and dogs, significantly impairing their social interactions and cognition. In humans, presbycusis involves changes in peripheral and central auditory systems, with central changes potentially occurring independently. While peripheral presbycusis in dogs is well-documented, resear...

Age-related decline in mobility and cognition are associated with cellular senescence and NAD + depletion in dogs and people. A combination of a novel NAD + precursor and senolytic, LY-D6/2, was examined in this randomized controlled trial. Seventy dogs with mild to moderate cognitive impairment were enrolled and allocated into placebo, low or full...

Cultural transmission of breed-specific beliefs about canine pain sensitivity occurs during veterinary education and training. However, breed-specific beliefs held by veterinarians do not align well with experimental measures of pain observed across dog breeds and are unlikely to be helpful in clinical decision making. The aim of the present study...

Practical relevance Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and are effective for the management of pain in cats. These Guidelines will support veterinarians in decision-making around prescribing NSAIDs in situations of chronic pain, to minimise adverse effects and optimise pain management. Information is provided on mechanis...

Age-related decline in mobility and cognition are associated with cellular senescence and NAD+ depletion in dogs and people. A combination of a novel NAD+ precursor and senolytic, LY-D6/2 was examined in this randomized controlled trial. Seventy dogs were enrolled and allocated into placebo, low or full dose groups. Primary outcomes were change in...

Simple Summary Imepitoin is a medication that can be used to treat anxiety in dogs. Previous studies have shown that imepitoin when given at a dose of 30 mg/kg PO BID (milligram per kilogram of body weight by mouth twice a day), can reduce noise-related anxiety in dogs. However, this dosage may be higher than needed for some dogs. We aimed to deter...

Simple Summary The prevalence of dental disease and cognitive decline in elderly dogs is extremely high, and, given the known relationship between dental disease and Alzheimer’s Disease in people, this study sought to describe the changes in oral microbiota in aged pet dogs over time. By sequencing oral swabs, we were able to identify bacterial and...

Dog breed stereotypes are frequently used to inform people’s expectations about canine behavior, despite evidence that breed is largely uninformative in predicting individual dog behavior. Further, these beliefs differ among populations. However, it remains unknown how ratings of warmth toward a breed are associated with ratings of other social beh...

Over 95% of veterinarians report believing that dog breeds differ in pain sensitivity. Ratings made by veterinarians differ from those of the general public, suggesting these beliefs may be learned during veterinary training or clinical experiences. Therefore, the current study’s primary objective was to evaluate dog breed pain sensitivity ratings...

Disturbances in the sleep–wake cycle are a debilitating, yet rather common condition not only in humans, but also in family dogs. While there is an emerging need for easy-to-use tools to document sleep alterations (in order to ultimately treat and/or prevent them), the veterinary tools which yield objective data (e.g. polysomnography, activity moni...

Background: Veterinarians hold distinct breed-specific pain sensitivity beliefs that differ from the general public but are highly consistent with one another. This is remarkable as there is no current scientific evidence for biological differences in pain sensitivity across dog breeds. Therefore, the present study evaluated whether pain sensitivi...

Introduction In humans, gait speed is a crucial component in geriatric evaluation since decreasing speed can be a harbinger of cognitive decline and dementia. Aging companion dogs can suffer from age-related mobility impairment, cognitive decline and dementia known as canine cognitive dysfunction syndrome. We hypothesized that there would be an ass...

Purpose To determine the association between age and retinal full-field electroretinographic (ERG) measures in companion (pet) dogs, an important translational model species for human neurologic aging. Methods Healthy adult dogs with no significant ophthalmic abnormalities were included. Unilateral full-field light- and dark-adapted electroretinog...

Introduction Sleep is fundamental for cognitive homeostasis, especially in senior populations since clearance of amyloid beta (key in the pathophysiology of Alzheimer's disease) occurs during sleep. Some electroencephalographic characteristics of sleep and wakefulness have been considered a hallmark of dementia. Owners of dogs with canine cognitive...

Here, we address Hansen Wheat et al.’s commentary in this journal in response to Salomons et al. Current Biology, 31(14), 3137–3144.E11, (2021). We conduct additional analyses in response to Hansen Wheat et al.’s two main questions. First, we examine the claim that it was the move to a human home environment which enabled the dog puppies to outperf...

Maintaining an active lifestyle is considered a hallmark of successful aging. Physical activity significantly reduces the risk of cognitive decline and Alzheimer’s disease in humans. However, pain and lack of motivation are important barriers to exercise. Dogs are a remarkable model for translational studies in aging and cognition as they are prone...

While much work has been done in the field of canine olfaction, there has been little exploration of hyposmia or anosmia. This is partly due to difficulties in reducing confounds like training history and environmental distraction. The current study describes a novel olfaction test using spontaneous search behavior in dogs to find a hidden food tre...

Poster presented at the ESVN-ECVN 34th Symposium. Mallorca Spain, September 2022

Poster presented at the 2022 Triangle SfN meeting

Background Elderly people with presbycusis are at higher risk for dementia and depression than the general population. There is no information regarding consequences of presbycusis in dogs. Objective Evaluate the relationship between cognitive function, quality of life, and hearing loss in aging companion dogs. Animals Thirty‐nine elderly compani...

Aging is associated with impairment in postural control in humans. While dogs are a powerful model for the study of aging, the associations between age and postural control in this species have not yet been elucidated. The aims of this work were to establish a reliable protocol to measure center of pressure excursions in standing dogs and to determ...

Biological aging is the single most important risk factor for disease, disability, and ultimately death in geriatric dogs. The effects of aging in companion dogs also impose significant financial and psychological burdens on their human caregivers. The underlying physiologic processes of canine aging may be occult, or early signs of aging may be ig...

Background Aging dogs may suffer from canine cognitive dysfunction syndrome (CCDS), a condition in which cognitive decline is associated with amyloid pathology and cortical atrophy. Presumptive diagnosis is made through physical examination, exclusion of systemic/metabolic conditions, and completion of screening questionnaires by owners. Objective...

Canine Cognitive Dysfunction Syndrome (CCDS) is a syndrome of progressive cognitive decline comparable to Alzheimer's Disease. The sustained gaze test captures attention loss associated with CCDS in laboratory settings, and adapting the sustained gaze test for use by owners at home could greatly increase the data generated on CCDS. We hypothesized...

Background Frunevetmab, a felinized antinerve growth factor monoclonal antibody, effectively decreases osteoarthritis (OA) pain in cats. Objective To evaluate the efficacy of frunevetmab given at monthly intervals in a randomized, placebo‐controlled, parallel‐group, double‐blind superiority study. Animals Two hundred seventy‐five client‐owned cat...

Although we know that dogs evolved from wolves, it remains unclear how domestication affected dog cognition. One hypothesis suggests dog domestication altered social maturation by a process of selecting for an attraction to humans.1, 2, 3 Under this account, dogs became more flexible in using inherited skills to cooperatively communicate with a new...

The loss of a companion animal results in millions of pet owners grieving annually. To date, little information has been synthesized on the grief response and coping mechanisms of bereaved pet owners. The aim of this review was to examine the relationship between pet loss and owner grief response. Major themes included: factors that influence the g...

Background: Pain management for cats with degenerative joint disease (DJD) remains a critical unmet need. Recent work has shown promise for a feline-specific anti-nerve growth factor monoclonal antibody (frunevetmab) to deliver safe and effective pain management. Our objectives were to evaluate the efficacy and safety of frunevetmab administered tw...

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 j...

The main objective of this pilot clinical trial was to evaluate outcome measures for the assessment of the nonsteroidal anti-inflammatory drug (NSAID) robenacoxib in cats with degenerative joint disease-associated pain (DJD-pain). Otherwise healthy cats (n = 109) with DJD-pain entered a parallel group, randomized, blinded clinical trial. Cats recei...

HIV rapidly infects the central nervous system (CNS) and establishes a persistent viral reservoir within microglia, perivascular macrophages and astrocytes. Inefficient control of CNS viral replication by antiretroviral therapy results in chronic inflammation and progressive cognitive decline in up to 50% of infected individuals with no effective t...

** Full-text view-only SharedIt link: https://rdcu.be/b9o1a ** While our understanding of adult dog cognition has grown considerably over the past 20 years, relatively little is known about the ontogeny of dog cognition. To assess the development and longitudinal stability of cognitive traits in dogs, we administered a battery of tasks to 160 cand...

Objectives To characterize sleep and circadian rhythms of a sample population of healthy, dog-owning adults from North Carolina, USA. Methods Actigraphy was used to analyze sleep-wake patterns in forty-two dog owners from the Raleigh area in North Carolina. Sleep quotas, including sleep duration, efficiency, and fragmentation were measured alongsi...

Background: While often grouped with other noise aversions, fearful behaviour during storms is considered more complex than noise aversion alone. The objective here was to assess the effect of imepitoin for the treatment of storm anxiety in dogs. Methods: In this double-blind, placebo-controlled randomised study, eligible dogs completed a baseli...

While we know that dogs evolved from wolves through a process of domestication, it remains unclear how this process may have affected dog cognitive development. Here we tested dog (N=44) and wolf (N=37) puppies, 5-18 weeks old, on a battery of temperament and cognition tasks. Dog puppies were more attracted to humans, read human gestures more skill...

The study of companion (pet) dogs is an area of great translational potential, as they share a risk for many conditions that afflict humans. Among these are conditions that affect sleep, including chronic pain and cognitive dysfunction. Significant advancements have occurred in the ability to study sleep in dogs, including development of non-invasi...

Animal-assisted interventions (AAIs) use human-animal interactions to positive effect in various contexts including cancer care. As the first installment of a 2-part series, this systematic literature review focuses on the research methods and quantitative results of AAI studies in oncology. We find methodological consistency in the use of canines...

To characterize the early ontogeny of dog cognition, we tested 168 domestic dog, Canis familiaris, puppies (97 females, 71 males; mean age = 9.2 weeks) in a novel test battery based on previous tasks developed and employed with adolescent and adult dogs. Our sample consisted of Labrador retrievers, golden retrievers and Labrador × golden retriever...

Animal-assisted interventions (AAIs) can improve patients’ quality of life as complementary medical treatments. Part I of this 2-paper systematic review focused on the methods and results of cancer-related AAIs; Part II discusses the theories of the field’s investigators. Researchers cite animal personality, physical touch, physical movement, distr...

HIV rapidly infects the central nervous system (CNS) and establishes a persistent viral reservoir within microglia, perivascular macrophages and astrocytes. Inefficient control of CNS viral replication by antiretroviral therapy results in chronic inflammation and progressive cognitive decline in up to 50% of infected individuals with no effective t...

This paper details the development of a novel wireless heart rate sensing system for puppies in training as guide dogs. The system includes a harness with on-board electrocardiography (ECG) front-end circuit, inertial measurement unit and a micro-computer with wireless capability where the major research focus of this paper was on the ergonomic des...

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 i...

We argue that there is currently an under-reporting of the ways in which pain can be associated with problem behavior, which is seriously limiting the recognition of this welfare problem. A review of the caseloads of 100 recent dog cases of several authors indicates that a conservative estimate of around a third of referred cases involve some form...

Animal-assisted interventions (AAI) use human-animal interactions to positive effect in various contexts including cancer care. This systematic literature review is the first part of a two-part paper series focusing on the research methods and quantitative results of AAI studies in oncology. We find methodological consistency in the use of canines...

Animal-assisted interventions (AAI) are a unique class of complementary medical treatments that can improve a patient’s quality of life, both physically and psychologically. Part I of this two-paper systematic literature review series focused on the study methods and quantitative results of researchers in this field. We continue this in-depth revie...

In humans, pain due to osteoarthritis has been demonstrated to be associated with insomnia and sleep disturbances that affect perception of pain, productivity, and quality of life. Dogs, which develop spontaneous osteoarthritis and represent an increasingly used model for human osteoarthritis, would be expected to show similar sleep disturbances. F...

Cognitive bias tests have been used to measure affective states in dogs. The results may also involve spatial learning and memory when location is used as the cue. In this study, we evaluated the performance of 16 Labrador retriever dogs with a cognitive bias test that used spatial location as the cue and compared the results to the dogs’ performan...

Environmental enrichment is critical for alleviating stress in laboratory felines. However, there is a paucity of information about suitable enrichment for cats. This study aimed to determine preferred enrichment options of individually-housed, castrated male domestic short hair cats (Felis catus) used in a longitudinal study of the effects of chro...

Animal-assisted therapies (AAT) are becoming increasingly common to help hospitalized patients, especially in oncology units. There is a critical need for methods and technologies that can enable a quantifiable understanding of AAT to objectively demonstrate its efficacy and improve its efficiency. In this paper, we present our preliminary efforts...

Indoor housing of cats is associated with a higher incidence of multiple diseases, including obesity. Increased exercise is often recommended as a method of creating or increasing the negative energy balance required for weight loss. Food-dispensing toys have been suggested as a method of increasing cat activity and providing environmental enrichme...

Challenges in the clinical assessment of feline osteoarthritis (OA)-related pain and disability impede diagnosis and treatment of the disease. A pain scale was developed for use by cat owners and caretakers, the Montreal Instrument for Cat Arthritis Testing - Caretaker/Owner (MI-CAT(C)). Following content validation and a pilot assessment (n=11 cat...

Aggressive behavior in dogs poses public health and animal welfare concerns, however the biological mechanisms regulating dog aggression are not well understood. We investigated the relationships between endogenous plasma oxytocin (OT) and vasopressin (AVP)—neuropeptides that have been linked to affiliative and aggressive behavior in other mammalia...

Trazodone hydrochloride is an atypical antidepressant that has entered clinical use for dogs and cats for a variety of indications. These include management of anxiety disorders, facilitation of travel and veterinary examinations, and facilitation of calm behavior in hospitalized and postoperative patients. Despite the increasingly common use of tr...

Safety pharmacology studies in dogs often integrate behavioral assessments made using video recording with physiologic measurements collected by telemetry. However, whether merely wearing the telemetry vest affects canine behavior and other parameters has not been evaluated. This pilot study assessed the effect of a telemetry vest on behavioral and...

Aggressive behavior in dogs poses public health and animal welfare concerns, however the biological mechanisms regulating dog aggression are not well understood. We investigated the relationships between endogenous plasma oxytocin (OT) and vasopressin (AVP) – neuropeptides that have been linked to affiliative and aggressive behavior in other mammal...

Safety pharmacology studies in dogs often integrate behavioral assessments made using video recording with physiologicmeasurements collected by telemetry. However, whether merely wearing the telemetry vest affects canine behavior and otherparameters has not been evaluated. This pilot study assessed the effect of a telemetry vest on behavioral and p...

A literature review identified six placebo-controlled studies of analgesics in client-owned cats with degenerative joint disease-associated pain. Five studies with 96 cats had available data. Caregiver responses on a clinical metrology instrument, Client-Specific Outcome Measure (CSOM), were compared to measured activity. Cats were categorised as ‘...

Introduction and objectives Accelerometry is used as an objective measure of physical activity in humans and veterinary species. In cats, one important use of accelerometry is in the study of therapeutics designed to treat degenerative joint disease (DJD) associated pain, where it serves as the most widely applied objective outcome measure. These a...

Activity (A) and intensity (B) profiles for cats in the two DJD groups. Log transformed activity for all cats is shown in gray with time (in hours) along the horizontal axis. The group mean for activity and intensity are shown for the Low-dose study (red) and FMPI study (yellow). (TIF)

Results of FPCA for Intensity for the Normal cats. (A) The top three eigenfunctions of intensity profiles for activity during the weekend (black) and weekday (blue). The first component describes approximately 40% of the total variance for both weekends and weekdays and picks up the two peaks seen in the activity profiles. (TIF)

Functional regression analysis for intensity in the DJD group. Depicted are the smooth effects of Age (years), BCS, AGE*BCS (standard deviations away from the mean), standardized TDJD score and TPain score on the intensity of DJD cats, when model (2) is assumed. Results are shown for weekends in the top row and weekdays in the bottom row, with func...

Results of FPCA for Intensity for the DJD cats. The top three eigenfunctions of intensity profiles for activity during the weekend (dark blue) and weekday (light blue). The first component describes approximately 34% of the total variance for the weekends and approximately 37% for the weekdays and picks up the two peaks seen in the activity profile...

Functional regression analysis for intensity in the Normal group. Depicted are the smooth effects of Age (years, left panels), BCS (middle panels) and AGE*BCS (standard deviations away from the mean, right panels) on the intensity of Normal cats, when model (1) is assumed. Results are shown for weekends in the top row and weekdays in the bottom row...

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 Prospective clinical study. Animals Fifty-four client owned dogs (OA, n = 31; Controls, n = 23). Methods Mechanical [(Electronic von Frey (...

OBJECTIVE To determine attitudes of small animal practitioners toward veterinary clinical trials and variables influencing their likelihood of participating in such trials. DESIGN Cross-sectional survey. SAMPLE Small animal practitioners with membership in 1 of 2 online veterinary communities (n = 163 and 652). PROCEDURES An online survey was devel...

Degenerative joint disease is common in cats, with signs of pain frequently found on orthopedic examination and radiographs often showing evidence of disease. However, understanding of the pathophysiology of degenerative joint disease and associated pain remains limited. Several cytokines have been identified as having a role in pain in humans, but...

Background: Degenerative joint disease (DJD) is highly prevalent in cats, and pain contributes to morbidity. In humans, alterations of cytokine concentrations have been associated with joint deterioration and pain. Similar changes have not been investigated in cats. Cytokine concentrations can be measured using multiplex technology with small samp...

OBJECTIVE To evaluate the efficacy of a single dose of trazodone for reducing anxiety in cats during transport to a veterinary hospital and facilitating handling during veterinary examination. DESIGN Double-blind, placebo-controlled, randomized crossover study. ANIMALS 10 healthy client-owned cats (2 to 12 years of age) with a history of anxiety du...

Background: Neutralizing antibodies against nerve growth factor (NGF) are analgesic in rodent models, naturally occurring degenerative joint disease (DJD) pain in dogs, and chronic pain in humans. Objectives: To evaluate the efficacy of a fully felinized anti-NGF antibody (NV-02) for the treatment of DJD pain and mobility impairment in cats. An...

Background: In veterinary clinical pain studies, there is a paucity of data on test-retest variability in Clinical Metrology Instruments (CMIs), and it is unknown whether CMIs should be administered using independent (respondents not permitted to see previous answers) or dependent (respondents shown previous answers) interviewing. Objectives: To...

Osteoarthritis (OA)-associated pain is a leading cause of disability. Central Sensitization (CS), as a result of OA, is recognized as an important facet of human patients' chronic pain and has been measured in people using quantitative sensory threshold (QST) testing. The spontaneous canine OA model has been suggested as a good translational model,...

A critical aspect of canine explosive detection involves the animal's ability respond to novel, untrained odors based on prior experience with training odors. In the current study, adult Labrador retrievers (N = 15) were initially trained to discriminate between a rewarded odor (vanillin) and an unrewarded odor (ethanol) by manipulating scented obj...

Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that can be used in the target population of client owned cats. The objectives of this study were to evaluate low-...