R01AR086796

LEVERAGING INTER-INDIVIDUAL DIFFERENCES IN WALKING PAIN AND IMPAIRMENT TO ELUCIDATE WHOLE-PERSON MECHANISMS OF KNEE OSTEOARTHRITIS - PROJECT SUMMARY/ABSTRACT KNEE OSTEOARTHRITIS (OA) IS A COMMON AND DEBILITATING CONDITION, AFFECTING MILLIONS IN THE UNITED STATES OF AMERICA. FROM 1990 TO 2020, OA RANKED AS THE 14TH HIGHEST CAUSE OF AGE-ADJUSTED YEARS LIVED WITH DISABILITY AND IS A SERIOUS DISEASE DUE TO DISABILITY, WHICH INCREASES MORTALITY. ALTHOUGH THE IMPACT OF KNEE OA ON THE POPULATION LEVEL IS TREMENDOUS, THERE ARE SIGNIFICANT INTER-INDIVIDUAL DIFFERENCES IN PAIN AND FUNCTIONAL IMPAIRMENT. WEIGHT- BEARING, MOVEMENT-EVOKED PAIN EXPERIENCED DURING WALKING RANGES FROM MINIMAL TO SEVERE. SOME PATIENTS MAINTAIN MOVEMENT, EXPERIENCING A RANGE OF PAIN INTENSITIES, WHILE OTHERS ARE IMMOBILIZED DUE TO PAIN. FACTORS CONTRIBUTING TO INTER-INDIVIDUAL DIFFERENCES ARE UNCLEAR, IN PART DUE TO THE LACK OF STUDIES EXAMINING THE “WHOLE PERSON,” INCLUDING BIOLOGICAL, PSYCHOLOGICAL, AND SOCIAL FACTORS RANGING FROM THE KNEE AND NERVOUS SYSTEM TO SOCIAL ENGAGEMENT. IDENTIFYING BIOPSYCHOSOCIAL MECHANISMS UNDERLYING INTER-INDIVIDUAL DIFFERENCES IN PAIN AND MOVEMENT IS A CRITICAL UNMET NEED IN KNEE OSTEOARTHRITIS. THESE MECHANISMS REPRESENT OPPORTUNITIES FOR NOVEL TREATMENT TARGETS, PERSONALIZED TREATMENTS, AND AN AVENUE TO IMPROVE OVERALL HEALTH BY MAINTAINING OR IMPROVING PHYSICAL ACTIVITY KNOWN TO REDUCE MORBIDITY AND MORTALITY. THIS APPLICATION’S OBJECTIVE IS TO ELUCIDATE “WHOLE PERSON” BIOPSYCHOSOCIAL MECHANISMS OF MOVEMENT-EVOKED PAIN AND PAIN LIMITATIONS ON FUNCTION IN KNEE OA. INFORMED BY A THEORETICAL FRAMEWORK OF MOVEMENT-EVOKED PAIN, PRELIMINARY DATA DEMONSTRATE THAT SENSORY PROCESSING AND PAIN PREDICTION FACTORS CONTRIBUTE TO WALKING PAIN IN KNEE OA, MEASURED USING THE 6-MINUTE WALK TEST (6MWT). OVERLAPPING AND DISTINCT FACTORS PREDICTED FUNCTIONAL IMPAIRMENT, DEFINED AS DISTANCE WALKED ON THE 6MWT. USING CONCURRENT AMBULATORY BRAIN IMAGING AND GAIT BIOMECHANICS DURING 6MWT, PATTERNS OF PAIN WITH WALKING AND PAIN-LIMITING WALKING PERFORMANCE EMERGED. THESE PRELIMINARY DATA SUGGEST THAT THE LAB-BASED APPROACH TO UNDERSTAND FUNDAMENTAL “WHOLE-PERSON” MECHANISMS OF MOVEMENT EVOKED PAIN AND FUNCTIONAL IMPAIRMENT SHOWS PROMISE. IN THE PROPOSED OBSERVATIONAL STUDY, THE FIRST SPECIFIC AIM IS A COMPREHENSIVE DATA COLLECTION IN A LARGE SAMPLE OF KNEE OA PATIENTS, INCLUDING KNEE JOINT MRI AND DETAILED BIOMECHANICS ASSESSMENTS. THE SECOND AIM WILL IDENTIFY KEY FACTORS ASSOCIATED WITH KNEE PAIN INCREASES DURING WALKING ON THE 6MWT AND FOLLOWING EXERCISES EMULATING INITIAL PT EVALUATION. THE THIRD AIM WILL IDENTIFY KEY FACTORS ASSOCIATED WITH REDUCED FUNCTION ON THE 6MWT AND IDENTIFY HOW PAIN AND GAIT RELATE OVER TIME DURING PHYSICAL ACTIVITY. PARAMETRIC HYPOTHESIS TESTING AND DATA-DRIVEN, MACHINE-LEARNING METHODS WILL BE APPLIED TO THIS RICH DATASET. PAIN PREDICTION MECHANISMS ARE ANTICIPATED TO PLAY A LARGE ROLE AND REPRESENT A NOVEL TREATMENT TARGET. OVERALL, IDENTIFICATION OF KEY FACTORS UNDERLYING INTER-INDIVIDUAL DIFFERENCES IN MOVEMENT-EVOKED PAIN IN KNEE OA WILL REDUCE PAIN, FUNCTIONAL IMPAIRMENT, AND MORBIDITY AND MORTALITY, BROADLY ALIGNING WITH THE MISSION OF THE NIH AND SPECIFICALLY THE GOAL OF NIH HEAL INITIATIVE TO ENHANCE PAIN MANAGEMENT.

University Of Pittsburgh - Of The Commonwealth System Of Higher Education

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 INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM 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.

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]

Pittsburgh, Pennsylvania 152221808 United States

Single Zip Code

HEAL Initiative: Understanding Individual Differences in Human Pain Conditions (R01 - Clinical Trial Optional) (RFA-NS-25-020)