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Margaret Gruen

Assoc Professor

CVM Main Building C289


Dr. Gruen completed her veterinary degree at the University of Illinois. She came to North Carolina State University for an internship followed by a residency in veterinary behavior. She completed a Masters in Veterinary Public Health and became a board-certified veterinary behaviorist. After a few years on the faculty at NCSU, she decided to pursue a PhD with a focus on understanding the behaviors associated with pain in cats with naturally-occurring arthritis. She then spent two years at Duke University, where she co-directed the Canine Cognition Center, and has now returned to North Carolina State University as an Associate Professor of Behavioral Medicine.

Area(s) of Expertise

Animal Behavior, Chronic Pain, Welfare, Cognition, Anxiety


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Date: 08/01/23 - 7/31/25
Amount: $109,129.00
Funding Agencies: American Kennel Club Canine Health Foundation

In the United States, roughly 68 million veterinary visits are adversely affected by fearful behavior annually with negative consequences for canine welfare. Dog characteristics account for only a small portion (<7%) of the fear experienced in the clinical environment. It is critical that we address this knowledge gap regarding what drives fearful behavior in the clinic. We postulate that pain catastrophizing may be the missing factor. Pain catastrophizing is a cognitive and emotional response toward actual or anticipated pain, often characterized in humans by verbal reports and behavioral changes. People who are high in pain catastrophizing are at higher risk of pain-related interference in activity, development of chronic pain, and have worse health outcomes across a spectrum of diseases. In pediatric medicine, pain catastrophizing occurs in children and results in higher reported pain intensity scores and greater anxiety. Additionally, childrens??? pain experience is affected by caregivers who catastrophize about their child???s pain. Using the pediatric/caregivers model, we hypothesize that pain catastrophizing can be quantified in dogs using our novel experimental paradigm and is positively associated with owner catastrophizing about their dog???s pain. Establishing a measure of pain catastrophizing in dogs and understanding the owner influence on the phenomenon would be a major advance for veterinary medicine ??? specifically in pain management and behavioral health and welfare. Ultimately, our work will improve health outcomes including surgical recovery and management of chronic pain conditions ??? both of which have been shown in humans to be negatively affected by pain catastrophizing.

Date: 07/01/23 - 6/30/25
Amount: $249,062.00
Funding Agencies: Morris Animal Foundation

Frailty is a clinical state in which reserves are limited, with poor response to stressors, increasing risk of death. In people it is defined by assessing 5 domains: unintentional weight loss, weakness, exhaustion, slow walking speed and low activity levels. While frailty is a central component of geriatric human patient assessment, the concept of frailty is underutilized in veterinary medicine. We have developed a simple frailty phenotype that uses owner questionnaires (given end of life decisions are made by owners) to assess frailty domains, and hands-on assessment of body and muscle condition score by a clinician. Our frailty phenotype is highly accurate at predicting 6-month death rate; dogs that are frail in 2 or more of the 5 domains have a 6-month mortality rate of >60%. We would like to leverage this phenotype to design clinical trials targeting frailty domains. However, there is a paucity of data on progression of frail dogs. Moreover, there are no data published that quantify the response of frail dogs to physical rehabilitation. The consequent knowledge gaps make trial design challenging. In this study we will follow a cohort of 30 dogs with frailty in one or more domains over a 6-month period, recording their frailty status, pain levels, attention span, body condition, stability when standing and walking speed at time 0, 1, 3 and 6 months. We will match these dogs to a 30-dog cohort with similar age and frailty status that receive a customized rehabilitation regimen with daily at home exercise combined with 3 months of once weekly in house exercise targeting aerobic capacity, strength and balance. All dogs will have pain control optimized at study start. Data collected from cohort 1 will describe rate of change within the frailty domains and the functional measures of cognition, stability and mobility. The progression of cohort 2 will be examined in the same way to identify domains with a response to exercise. The progression of both cohorts will be compared using repeated measures logistic regression. The overarching aim is to facilitate future clinical trials through generation of descriptive data on frailty progression, and identification of promising exercises.

Date: 02/01/19 - 1/31/25
Amount: $928,275.00
Funding Agencies: National Institutes of Health (NIH)

Increasingly, clinical studies show that service and companion dogs can have a significant positive impact on children, adolescents, and adults with physical and mental disabilities. Unfortunately, there is a finite supply of service dogs and the growth potential of this supply is limited. The main limitation is the 50-70% attrition rate of dogs bred, raised and trained to be companion or service animals. The high attrition rate makes these animals costly and leads to long waiting lists of those in need. There is a clear need for systematic research that helps identify why some dogs are successful while some are not, that then leads to a larger supply of certified dogs to meet the demand. A revolution in our understanding of dog cognition has occurred in the past decade, with previous work by our group linking individual differences in cognition to working dog performance in adults. We propose to combine the resources of the Duke Canine Cognition Center, the NC State College of Veterinary Medicine and Canine Companion for Independence (CCI) to characterize the development of the cognitive traits that our previous work has shown predicts success in service dogs. First, we will detail how these cognitive traits, and their physiologic correlates, develop in CCI dogs using a longitudinal design during the critical period of brain development from 8-20 weeks of age. Second, to test for the influence of different but common service dog rearing strategies on these skills we will test CCI puppies being reared in human homes or together with same age peers on a college campus. In studying the cognitive abilities of service dogs we will develop a better understanding of what psychological mechanism(s) successful service dogs rely on or are constrained by when helping humans. We can then use this information to better predict which puppies will be successful service dogs ?????????????????? improving the success of training while increasing the potential number of service dogs available.

Date: 06/04/21 - 12/31/24
Amount: $118,263.00
Funding Agencies: Boehringer Ingelheim Vetmedica, Inc. (BIVI)

To evaluate efficacy and safety of imepitoin in comparison to placebo for the control of anxiety and fear associated with noise phobia in dogs. The aim is to evaluate the efficacy of imepitoin treatment compared to placebo over a prolonged treatment period applying a dosing scheme with low dose start and potential dose increase

Date: 11/15/21 - 9/30/24
Amount: $451,044.00
Funding Agencies: Animal Biosciences

Hypothesis: Treatment of aging dogs by oral administration of a senolytic and NAR supplement will stabilize or improve their owner perceived quality of life (QOL), activity and mobility levels, muscle mass and attention span when compared to dogs receiving a placebo. Objectives 1. Recruit 40 dogs meeting inclusion criteria regarding age, presence of co-morbidities, and level of cognitive performance. 2. Obtain baseline data on QOL, physical examination, routine blood work and UA, activity, and attention span. 3. Randomize to one of 2 treatment groups and initiate treatment and adverse event monitoring. 4. Repeat testing at 1, 3 and 6 months post treatment. 5. Determine longitudinal changes in QOL, activity, attention span.

Date: 03/01/20 - 8/31/23
Amount: $104,147.00
Funding Agencies: American Kennel Club Canine Health Foundation

Our recent survey found that both veterinarians and members of the public believe that dog breeds differ in their sensitivity to pain. However, whether or not breed differences in pain sensitivity actually exist has never been investigated previously. These beliefs could negatively impact the recognition and treatment of pain in the dog population and result in unnecessary suffering, particularly for dog breeds that are viewed as less sensitive to pain. We believe that dogs have similar pain sensitivity thresholds, regardless of what breed they are, but that perceptions about breed-based differences in pain sensitivity affect ratings of pain and the clinical recognition and treatment of pain. To investigate this, we will use a novel and innovative three-pronged approach. First, we will review records from veterinary hospitals to identify differences in pain scores assigned to dogs of different breeds. Second, we will use a survey to evaluate whether conditions are rated as more or less painful, depending on the breed of dog. Third, we will use non-invasive sensory testing to directly measure pain sensitivity across different breeds, to determine whether breed differences in pain sensitivity actually exist. This work is critical because real differences in sensory thresholds between different breeds may exist; if so, this would lay the foundation for further work to understand genetic differences in pain sensitivity and further understanding of pain in dogs. However, if no differences exist, then the impact of the perception of breed differences must be understood so that we can ensure that dogs of every breed are getting appropriate pain management.

Date: 08/01/21 - 7/31/22
Amount: $74,186.00
Funding Agencies: National Institutes of Health (NIH)

Globally this year, there will be an estimated 650,000 new human head and neck cancer (HNC) diagnoses.1 Half of those people will be cured with intensive combinations of surgery, radiation therapy and chemotherapy. But along their path towards a cure, essentially all of those patients will experience oral mucositis (OM) and discomfort. Indeed, significant treatment-associated pain is reported by 70% of HNC patients undergoing definitive radiotherapy, and 60% of patients report persistent pain for at least six months following treatment.2,3 OM occurs in nearly all patients who receive radiotherapy, and, in 10-25%, an interruption or modification in treatment is required. These treatment delays worsen local tumor control and overall survival time.4 To improve comfort and avoid treatment delays, effective analgesics are needed. Development of effective and appropriately targeted analgesics will require deep knowledge of the underlying pain signaling mechanisms that are activated by HNC treatment; however, there has been essentially no research in this area. Anecdotally, some HNC patients report cold sensitivity or pain associated with the development of OM. This observation led to our preliminary studies and the discovery that a critical component of acute orofacial radiation-associated pain is a signaling pathway mediated by neurons that express the TRPM8 (transient receptor potential melastatin family member 8) ion channel. Previously, this pathway has been associated with ????????????????cold pain.??????????????? We have evidence from mouse models that: ???????????????? Oral irradiation causes local release of a neurotrophic factor called artemin (ARTN), ???????????????? ARTN binds its receptor (GFR????????3) on free nerve endings in the mouth, and ???????????????? GFR????????3 activates TRPM8 in trigeminal sensory neurons, thus resulting in cold sensitivity and pain.

Date: 04/01/19 - 12/31/20
Amount: $2,500.00
Funding Agencies: Fear Free, LLC

Cat owners often perceive that veterinary visits are stressful for their cats. This has led to fewer cats presenting to the veterinary clinic for routine examination. A fast-acting, short duration medication that can decrease anxiety would improve cat welfare and allow for less stressful veterinary evaluations necessary for monitoring health. Although there are some therapies that have been suggested for this purpose, they have limitations. The usefulness of the therapy may be variable, may cause serious side effects, or may cause unwanted sedation. A new formulation of a therapeutic intervention, dexmedetomidine oromucosal gel (Sileo?????????), is applied to the gums or in the cheek pouch. This FDA-approved product has shown promise in decreasing anxiety during veterinary examination in dogs. A study of this product in cats by our research team has shown that this drug is safe and well tolerated. The proposed study will assess this product??????????????????s effect on decreasing anxiety compared to a placebo control in client-owned cats. In addition, this study will measure this product??????????????????s effect on cat ability to be handled, aggression, sedation, and health measurements such as heart rate, breathing rate, body temperature and blood pressure. This new dexmedetomidine gel formulation may be an effective means to decrease anxiety in cats during veterinary examination, thereby improving feline health and welfare.

Date: 01/01/19 - 12/31/20
Amount: $74,194.00
Funding Agencies: Zoetis, LLC

The objectives of this project are to develop two critical instruments for the detection, monitoring, and treatment of cats with chronic musculoskeletal disease. The first objective is to produce a sensitive and specific checklist (FMPC) to identify cats suffering musculoskeletal pain. The FMPC will facilitate the identification of cats that are highly likely to be suffering musculoskeletal pain. It will be easily incorporated into practices, and will facilitate education and awareness of owners around musculoskeletal pain, and concurrently facilitate initiation of conversations around musculoskeletal health. To develop the FMPC, we will determine the behaviors of cats that are most associated with clinical pain and radiographic disease. These will then be incorporated into a user friendly screening checklist. The second objective is to develop the final version of the Feline Musculoskeletal Pain Index (FMPI). This will be a companion instrument, with questions and scoring to allow determination of severity, monitor progression, and evaluate response to treatment.??????????????????????????????????????????????????????

Date: 11/12/18 - 12/15/20
Amount: $23,585.00
Funding Agencies: Zoetis, LLC

Noise aversion can be a progressive condition if left untreated or treated inappropriately. To date, several medications demonstrate alleviation of the signs of noise aversion, but none have been shown to completely relieve the signs and reduce need for further treatment. The objective of this study is to assess the efficacy and safety SILEO when administered repeatedly over several adjacent noise events to relieve the signs of noise aversion and to determine, if repeated dosing will preclude the need for additional treatment. Types of` noises, duration, intensity, frequency, type of signs severity of signs, and various environmental factors will be recorded to determine what factors contribute to the response.

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