Serum cytokines induced by performance of repetitive tasks and their relationship to sickness responses

Work-related repetitive strain injury (RSI), one of the work-related musculoskeletal disorders, is the most commonly reported occupational illness, yet the pathophysiological mechanisms are not yet clear. Using our unique RSI animal model, pathophysiological tissue responses can be examined simultaneously with behavioral responses that serve as indicators of sensorimotor function. Studies in humans and with this animal model have shown that prolonged performance of repetitive tasks leads to declines in grip strength and increased of serum pro-inflammatory cytokines, both valuable biomarkers of underlying tissue injuries. Identification of biomarkers would help to elucidate the time course of the inflammatory stage of these disorders and disease progression.;Sickness responses/behaviors, normal responses and behaviors occurring as a consequence of infection or illness, are responsible for re-organizing perceptions and actions to enable individuals to respond appropriately to the infection, injury and other illnesses. These behaviors can include malaise, fatigue, increased irritability and social withdrawal, behaviors that can be beneficial when ill for avoiding others and enhancing wellness. However, sickness behaviors can also include depression, sleep disorders and an enhanced perception of illness. Although recent studies have shown that circulating pro-inflammatory cytokines in serum may trigger sickness behaviors, only a few studies have examined if there is an association between work-related musculoskeletal disorders and subsets of sickness behavior; no one to date has elucidated any plausible biological cause of this association. Also, the combined effects of both aging and performance of repetitive tasks needs more evaluation since several epidemiological studies have shown a relationship between advancing age and susceptibility to musculoskeletal disorders.;Therefore, using female Sprague-Dawley rats, the aims of this dissertation project are to: 1) To determine if a systemic inflammatory response is maintained long-term in rats exposed to a moderate demand lever-pulling task with high repetition, low force (HRLF) requirements; if aging enhances this systemic inflammatory response and if this response correlates with functional motor declines; 2) To determine if performance of repetitive upper extremity tasks leads to the development of sickness behaviors (weight loss, decreased social interaction and increased aggression); 3) To determine if a relationship between repetitive upper extremity tasks lead to the development of dose- and age-dependent sickness behaviors, and, to determine if increased serum or brain inflammatory cytokines are plausible mechanisms for the induction of sickness behaviors in this model; and, lastly, 4) To determine if prophylactic or secondary systemic treatments with anti-inflammatory drugs (anti--tumor necrosis factor alpha or ibuprofen) reduces sickness behaviors in rats performing a high demand high repetition high force (HRHF) reaching and handle pulling task. This finding would be in further support of an underlying task-induced inflammatory mechanism contributing to these sickness behaviors. (Abstract shortened by UMI.).