Upper extremity repetitive motion disorders (RMDs) affecting the soft tissues of the neck, shoulders, arms, and hands are prevalent in the U.S. and throughout the world and impose a large economic burden for society. Unfortunately, effective treatments are still needed, especially preventive treatments as well as treatments to reverse tissue fibrosis. Fibrosis within and between the tissue structures in the upper limb is hypothesized to be a key factor in the motor dysfunction, increased discomfort, and pain and paresthesias observed in subjects with chronic RMDs. Therefore, our goal here is to use our well-established rodent model in which prolonged performance of high demand reaching and handle-pulling tasks initially induces early injury and inflammation, and later significant fibrosi in nerves, muscles and tendons, with persistent signs of pain and motor dysfunction, to investigate effective means of treatment. Manual therapy refers to a number of related therapies that are applied to patients using the practitioner's hands, such as massage, mobilization, and manipulation. Manual therapies are thought to prevent and/or disrupt fibrosis, thought to be causing the symptoms observed in people and rats with upper extremity MSDs, but there are little data to support these claims. Our preliminary experiments using a combination of modeled massage therapy (MMT) methods in our rat model revealed preventive effects on sensorimotor declines and fibrosis development. Here, we propose to further examine MMT with the goals of: 1) preventing, and 2) reversing the sensorimotor declines and fibrosis that develops in our model of work-related MSDs, 3) testing which components is this treatment are effective, and 4) understanding key neurobiological mechanisms of the observed effects. Specifically, our aims are: 1) Aim 1. Which component(s) of a modeled manual therapy (MMT) protocol lead to reductions in tissue fibrosis and sensorimotor declines in rats that performed a high repetition high force (HRHF) task across an 18 weeks period? 2) Will massage therapy reverse tissue fibrosis and sensorimotor declines that have already occurred in rats that have performed the HRHF task for 18 weeks? 3) How does the HRHF task, with or without MMT, impact discharge properties and sensitivities of nociceptors innervating the arm and hand? Our proposed study will be among the first to study manual therapy in an animal model of chronic RMDs and with scientific rigor. Our findings are expected to lead to novel and readily translatable therapeutic strategies for the clinical management of patients with RMDs. This work has strong potential for long-term, sustained impact on the field of preventive medicine and rehabilitative sciences.