R01AR085335

Innovative modeling of the biopsychosocial model in animals: Validation of outcomes for assessing emotional and cognitive domains affected by naturally-occurring chronic pain in dogs - Project abstract

Osteoarthritis (OA) is a major and growing public health problem that negatively impacts quality of life.

The prevalence of painful arthritis in the U.S. likely approaches ~90 million adults and clinical sequela of OA-associated pain include decreased mobility and compromised activity.

Importantly, the chronic pain experience in humans frequently includes profound and debilitating effects on the emotional state, with significant negative impacts on quality of life and function.

Consequences also include impaired performance on cognitive tasks, particularly those requiring working memory or attentional switching.

These effects compound the clinical picture, contributing to the pain-related depression, anxiety, and emotional distress (the 'experience' of chronic pain).

Research relying on rodent models is not translating into new, effective treatments.

One reason for the lack of translational success is that despite the clear importance of emotion and cognition in the human chronic pain experience, current models of chronic pain in animals frequently ignore these critical domains.

The major goal of the proposed studies is to bridge this 'model gap' and significantly advance translational research capability by developing and rigorously validating a battery of assays for assessment of emotions and cognitive function in the pet dog model of persistent OA pain.

Pet dogs with naturally occurring persistent OA pain are already considered a good model of the sensory-discriminative aspects of OA pain in humans; enhancing the capability of this model will allow researchers, for the first time, to access a clinically relevant full biopsychosocial animal model of persistent pain.

We will achieve this through developing, refining and rigorously validating (test-retest, structural, discriminative, responsiveness, and criterion validity) a battery of emotional and cognitive domain tests, benchmarking against validated measures of pain and the impact of pain.

Applying advanced statistical techniques, we will create a concise battery that can be feasibly performed in clinical research settings.

We bring together diverse expertise with proven track records of collaboration and established facility resources to successfully address this critical gap in modeling the pain experience of humans.

Successful completion of this proposed work will validate a highly clinically relevant biopsychosocial animal model of persistent musculoskeletal pain that has the potential to radically increase the translation of pre-clinical knowledge into effective, non-addictive analgesic treatments for humans suffering from persistent musculoskeletal pain.

North Carolina State University

THE NATIONAL INSTITUTE OF AND MUSCULOSKELETAL AND SKIN DISEASES (NIAMS) MISSION IS TO SUPPORT RESEARCH INTO THE CAUSES, TREATMENT, AND PREVENTION OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES, TRAINING OF BASIC AND CLINICAL SCIENTISTS TO CARRY OUT THIS RESEARCH, AND DISSEMINATION OF INFORMATION ON RESEARCH PROGRESS IN THESE DISEASES. THE EXTRAMURAL PROGRAM PROMOTES AND SUPPORTS BASIC, TRANSLATIONAL, AND CLINICAL STUDIES OF SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES, SKIN BIOLOGY AND DISEASES, BONE BIOLOGY AND DISEASES, MUSCLE BIOLOGY AND DISEASES, AND JOINT BIOLOGY AND DISEASES AND ORTHOPAEDICS. NIAMS SYSTEMIC RHEUMATIC AND AUTOIMMUNE DISEASES PROGRAMS ADDRESS BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH, INCLUDING CLINICAL TRIALS AND OBSERVATIONAL AND MECHANISTIC STUDIES, FOCUSED ON IMMUNE-MEDIATED ARTHRITIS AND AUTOIMMUNE-RELATED ACUTE AND CHRONIC DISORDERS IN ADULTS AND CHILDREN. NIAMS SKIN BIOLOGY AND DISEASES PROGRAMS SUPPORT BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH IN SKIN, INCLUDING BOTH COMMON AND RARE SKIN DISEASES. THESE PROGRAMS INCLUDE INVESTIGATIONS OF THE BASIC MOLECULAR, CELLULAR, AND DEVELOPMENTAL BIOLOGY OF SKIN, AS WELL AS STUDIES OF SKIN AS AN IMMUNE, SENSORY, ENDOCRINE, AND METABOLIC ORGAN. NIAMS BONE BIOLOGY AND DISEASES PROGRAMS SUPPORT RESEARCH ON THE CONTROL OF BONE FORMATION, RESORPTION, AND MINERALIZATION AS WELL AS THE EFFECTS OF SIGNALING MOLECULES ON BONE CELLS. THEY SUPPORT CLINICAL STUDIES OF INTERVENTIONS TO PREVENT FRACTURES ASSOCIATED WITH OSTEOPOROSIS AND RESEARCH INTO LESS COMMON BONE DISEASES. NIAMS MUSCLE BIOLOGY AND DISEASES PROGRAMS ENCOURAGE RESEARCH ON MUSCLE DEVELOPMENTAL BIOLOGY, GROWTH, MAINTENANCE, AND HYPERTROPHY, PHYSIOLOGY OF CONTRACTION, STRUCTURAL BIOLOGY OF THE CONTRACTILE APPARATUS, DISEASE MECHANISMS, BIOMARKERS AND OUTCOME MEASURES, AND DEVELOPMENT AND CLINICAL TESTING OF THERAPIES FOR CONDITIONS INCLUDING THE MUSCULAR DYSTROPHIES. NIAMS JOINT BIOLOGY, DISEASES, AND ORTHOPAEDICS PROGRAMS SUPPORT A BROAD SPECTRUM OF RESEARCH CENTERED ON THE INTERPLAY AMONG THE BODY'S MUSCLES, BONES, AND CONNECTIVE TISSUES. THEY ENCOURAGE TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH, MOLECULAR BIOLOGY, IMAGING, AND CLINICAL RESEARCH, AND THE TREATMENT AND PREVENTION OF ORTHOPAEDIC CONDITIONS. NIAMS PARTICIPATES IN THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAMS. THE SBIR PROGRAM IS INTENDED TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE STTR PROGRAM IS INTENDED TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INST

93.279 - Drug Abuse and Addiction Research Programs

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [HHS - NIH]

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Raleigh, North Carolina 27695 United States

Single Zip Code

HEAL Initiative: Development and Validation of Non-Rodent Mammalian Models of Pain(R01 Clinical Trial Not Allowed) (RFA-NS-22-070)