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Margaret Gruen DVM

Associate Professor of Behavioral Medicine

CVM Main Building C289

Bio

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

SPONTANEOUS ANIMAL DISEASE MODELS
Animal Behavior, Chronic Pain, Welfare, Cognition, Anxiety

Publications

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Grants

Date: 06/04/21 - 12/31/23
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 - 9/30/23
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 - 2/28/23
Amount: $104,147.00
Funding Agencies: American Kennel Club Canine Health Foundation, Inc.

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: 02/01/19 - 1/31/23
Amount: $748,494.00
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: 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 (GFRα3) on free nerve endings in the mouth, and ● GFRα3 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.

Date: 07/01/18 - 9/30/19
Amount: $209,455.00
Funding Agencies: US Dept. of Energy (DOE)

Investigators at Oak Ridge National Lab (ORNL) are interested in measuring physiological characteristics of dogs as they are exposed to environmental stimuli. We will develop 1) custom wearable sensing units capable of aggregating measurements from working dogs in controlled environments during experiments, 2) corpora of data from experiments conducted by ORNL in a format amenable for statistical analysis from ORNL, and 3) software to enable ORNL to extract and process the data describing those physiological measurements automatically. We will provide input into experimental design to facilitate effective use of sensing devices for analyzing physiological responses.

Date: 05/15/19 - 8/15/19
Amount: $5,000.00
Funding Agencies: Morris Animal Foundation

Canine cognitive dysfunction (CCD) is a neurobehavioral syndrome occurring in a significant portion of geriatric dogs and is attributed to pathological neurodegeneration of the brain1. In humans, neurodegeneration of the brain most commonly leads to a disorder known as Alzheimer's disease (AD). CCD shares many clinical and neuropathological characteristics with AD serving as a naturally-occurring model for AD2. Currently, diagnosis of CCD is dependent on recognition of behavioral signs and exclusion of other disease processes that may cause cognitive dysfunction. Moreover, not all senior dogs show behavioral changes consistent with CCD but may possess subclinical cognitive deficits that will progress to development of clinical CCD making diagnosis of the CCD even more arduous3. Considering the affected population, dogs affected with CCD are likely to have mobility impairments due to comorbidities that arise with aging. A glaring barrier for cognitive testing of geriatric dogs is that the current cognitive tests implemented on client-owned dogs rely on the patient to be ambulatory, which may not be possible for patients with impaired to no mobility. Currently a longitudinal clinical trial evaluating brain aging in geriatric dogs has been established and seeks to identify clinical biomarkers reflective of pathologic neurodegeneration which may be utilized for earlier diagnosis of CCD. A cognitive test will be developed and utilized in the longitudinal study to quantify and define cognitive deficits in dogs with limited to absent mobility. Use of this novel test will be beneficial for both the researcher and patient by eliminating unneeded stress and pain induced by movement, which will further reduce possibility for patient noncompliance. Data collected throughout the trial will be critical for greater understanding of the clinical manifestation and neuropathology of CCD as well as non-pathological neurological aging in geriatric dogs. Additionally, this study may provide novel methods for earlier diagnosis and quantification of disease progression in dogs affected with CCD. Ultimately, we hope our findings may provide a means to monitoring therapeutic response in clinical trials for dogs affected with CCD and distinguishing normal aging from pathological neurodegeneration.


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