The National Occupational Research Agenda stresses the importance of identifying work-related musculoskeletal disorder (WMSD) risk factors, understanding their exposure dependent nature, and identifying strategies to reduce their incidence and severity. We first examined behavioral changes after exposure to a low repetition low force (LRLF) reaching task for 12 weeks in young rats. We observed increased movement reversals in LRLF - week 8, indicative of a decline in fine motor control, and a small decrease in voluntary task participation in LRLF - week 12, compared to controls. This decline was associated temporally with a low-grade increase of macrophages in peripheral nerve and distal forelimb bones that correlated with nociceptive neurochemical increases in the spinal cord. We next examined motor behavior changes in young rats exposed to either a food retrieval high repetition negligible force (HRNF) task or a lever pulling high repetition low force (HRLF) reaching task. We found that both tasks led to motor declines, with more marked declines in fine motor control in the HRNF group. Thus, repetition, rather than the difference in force magnitude between the 2 tasks, appears to be the key factor in the induction of motor declines associated with repetitive motion injuries (RMIs). Also, these findings indicate that activities involving negligible force do not necessarily pose a lower risk than activities involving low force. Factors such as fine motor coordination requirements may even pose greater risks. Also, compared to the LRLF task, the high repetition tasks resulted in more motor performance declines, thus confirming exposure-dependency in the context of RMI. We also explored the effects of HRNF and HRLF tasks on supraspinatus tendon of young adult rats in 6 and 12 weeks. We found a small but non-significant elevation of ED1+ macrophages in 6 weeks. The supraspinatus tendon does not appear to develop as many pathological changes as forelimb flexor tendons (Barbe, et al., 2003) with task performance. Lastly, we examined the effects of performing HRLF tasks in aged rats. We found that aged rats demonstrate both declines in motor performance and pathological tissue changes over the course of 12 weeks of exposure to the HRLF lever pulling task. The observed declines in grip strength in aged trained control and HRLF rats over time suggest that both age and cumulative exposure to the repetitive task are factors in the development of WMSDs. Our findings suggest that additional study of exposure-dependency and risk factors is warranted. Deeper understanding of the relative contributions of various risk factors can help inform prophylactic programs and/or interventions for individuals who are at risk for, or suffer from, WMSDs.