This project will use a novel in vivo injury model for cumulative trauma disorder in the rat that encompasses the investigation of injury of tendosynovial, musculoskeletal and nerve tissues in the context of a repetitive, posturally constrained, voluntary hand and wrist-intensive motor behavior. This application proposes the use of this model to examine the exposure-response relationship between motor task repetition rate and physiological and behavioral indicators of injury. Such a model will be used in future studies of therapeutic interventions and preventive strategies for the management of cumulative trauma disorders. The proposed study has two specific aims: 1) To investigate the inflammatory and microtraumatic responses in the peripheral tissues both local and distant to the flexors of the paw and wrist (primary exposure site) under conditions of varied exposure intensities in a rat model of repetitive motion injury. The inflammatory changes to be investigated include production of inflammatory mediators, such as cytokines and COX2, and increases in inflammatory cells, such as macrophages. The microtraumatic changes to be investigated include fibrosis, compositional and structural alterations in tendosynovial and musculoskeletal tissues, presence of stress proteins, such as hsp 70, degradation of myelin, and a decrease in nerve conduction velocity of the median nerve. 2) To investigate motor performance responses under conditions of varied exposure intensities in a rat model of repetitive motion injury and their chronological relationship to the inflammatory and microtraumatic changes observed. The motor performance changes to be investigated include the ability of animals to maintain target repetition rate over time, their success in retrieving food pellets, maximum grip force, and forelimb movement patterns of reaching and grasping during food pellet retrieval. Adult Sprague-Dawley rats will be trained to repetitively retrieve food pellets with one forelimb by reaching through a narrow opening to a shelf at two target rates: a high repetition rate (15 seconds per reach, n=54) and a low repetition rate (45 seconds per reach, n=54). This task will be performed 2 hr/day, 3 day/wk for up to 8 weeks. Video recordings of the task will be made and reach movement patterns will be determined using a notation system and frame-by-frame trajectory reconstruction method. Reach repetition rate (RR) and success of pellet retrieval will be automatically recorded. At weeks 3 and weekly thereafter, subsamples of experimental and control animals (n=6-9) will undergo motor testing for grip strength, and will then be anesthetized for median nerve NCV testing or euthanized for microscopic examination of tendosynovial, musculoskeletal and peripheral nerve tissues both local and distant to the flexor aspect of the distal forelimb using haematoxylin and immunohistochemical staining. Comparisons in motor performance (i.e. reach movement patterns, RR, success and grip strength), NCV, and tissue morphology will be made between experimental and control animals. In addition, comparisons of NCV, grip strength and tissue morphology will be made between trained and untrained forelimbs of experimental animals. The relationship of these changes to task repetition rate will be analyzed across time.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR046426-02
Application #
6171487
Study Section
Special Emphasis Panel (ZAR1-AAA-A (M1))
Program Officer
Panagis, James S
Project Start
1999-09-01
Project End
2002-08-31
Budget Start
2000-09-01
Budget End
2002-08-31
Support Year
2
Fiscal Year
2000
Total Cost
$75,000
Indirect Cost
Name
Temple University
Department
Other Health Professions
Type
Schools of Allied Health Profes
DUNS #
057123192
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
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Reno, Philip L; Horton Jr, Walter E; Elsey, Ruth M et al. (2007) Growth plate formation and development in alligator and mouse metapodials: evolutionary and functional implications. J Exp Zool B Mol Dev Evol 308:283-96
Barr, Ann E (2006) Tissue pathophysiology, neuroplasticity and motor behavioural changes in painful repetitive motion injuries. Man Ther 11:173-4
Barbe, Mary F; Barr, Ann E (2006) Inflammation and the pathophysiology of work-related musculoskeletal disorders. Brain Behav Immun 20:423-9
Reno, Philip L; McBurney, Denise L; Lovejoy, C Owen et al. (2006) Ossification of the mouse metatarsal: differentiation and proliferation in the presence/absence of a defined growth plate. Anat Rec A Discov Mol Cell Evol Biol 288:104-18
Al-Shatti, Talal; Barr, Ann E; Safadi, Fayez F et al. (2005) Increase in inflammatory cytokines in median nerves in a rat model of repetitive motion injury. J Neuroimmunol 167:13-22
Barr, Ann E; Barbe, Mary F; Clark, Brian D (2004) Systemic inflammatory mediators contribute to widespread effects in work-related musculoskeletal disorders. Exerc Sport Sci Rev 32:135-42
Barr, Ann E; Barbe, Mary F (2004) Inflammation reduces physiological tissue tolerance in the development of work-related musculoskeletal disorders. J Electromyogr Kinesiol 14:77-85
Barr, Ann E; Barbe, Mary F; Clark, Brian D (2004) Work-related musculoskeletal disorders of the hand and wrist: epidemiology, pathophysiology, and sensorimotor changes. J Orthop Sports Phys Ther 34:610-27
Clark, Brian D; Barr, Ann E; Safadi, Fayez F et al. (2003) Median nerve trauma in a rat model of work-related musculoskeletal disorder. J Neurotrauma 20:681-95

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