DESCRIPTION: Chronic pain originating from the musculoskelatal system is a dominant cause of sick-leave in modem industry and can be a very disabling and troublesome condition for the individual. Although the cause of this problem in skeletal muscle is unknown, one of the most frequent situations in which muscle pain is experienced is in industrial workers who have to move repeatedly and/or forcibly. The cumulative trauma disorder (CTD) which results from repetitive movements is of special interest because these repeat-motion injuries are one of the most difficult to anticipate and prevent. Our studies in humans have shown that exposure to a single bout of repeated strains can lead to myofiber and fascial rupture without bleeding but accompanied by muscle pain, restricted motion, and loss of strength and power. Little is known about the effect of repeated strains on muscles or the dynamic components of repeated use such as velocity and acceleration, which produce injury resulting in CTD or CTD risk. Since variations in human exposure and response together with the necessity for repeated tissue sampling makes man unsuitable as a research subject, we have developed a rat model of repeated strain injury (CTD). Using this model, the present study is designed: (1) to produce muscle strain injury in rats with and without fatigue using a custom-built dynamometer which can result in pathologic fibers, (2) to measure TGF-beta and bradykinin in response to muscle injury with and without pathology, (3) to assess the role of TGF-beta in collagen production and 4) to assay for TGF-beta in the blood of strain injured rats. Pathologic muscle fibers associated with TGF-beta will be identified using immunohistochemical techniques. Collagen content will be measured by HPLC. Active and latent forms of TGF-beta 1 and TGF-beta2 and type I and III collagens will be quantified by Western blots. Insight into the factors and conditions producing muscle injury with pathology should provide a better understanding of the healing (adaptive) or failed-healing (pathologic) processes of muscle and aid in the design of preventative regimens for individuals in specific industrial settings.