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.
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