Forced Treadmill Running Reduces Systemic Inflammation Yet Worsens Upper Limb Discomfort in a rat model of Work-Related Musculoskeletal Disorders

Abstract

Background: Musculoskeletal disorders can result from prolonged repetitive and/or forceful movements. Performance of an upper extremity high repetition high force task increases serum pro-inflammatory cytokines and upper extremity sensorimotor declines in a rat model of work-related musculoskeletal disorders. Since one of the most efficacious treatments for musculoskeletal pain is exercise, this study investigated the effectiveness of treadmill running in preventing these responses. Methods: Twenty-nine young adult female Sprague-Dawley rats were used. Nineteen were trained for 5 weeks to pull a lever bar at high force (15 min/day). Thirteen went on to perform a high repetition high force reaching and lever-pulling task for 10 weeks (10-wk HRHF; 2 hrs/day, 3 days/wk). From this group, five were randomly selected to undergo forced treadmill running exercise (TM) during the last 6 weeks of task performance (10-wk HRHF+TM, 1 hr/day, 5 days/wk). Results were compared to 10 control rats and 6 rats that underwent 6 weeks of treadmill running following training only (TR-then-TM). Voluntary task and reflexive sensorimotor behavioral outcomes were assessed. Serum was assayed for inflammatory cytokines and corticosterone, reach limb median nerves for CD68+ macrophages and extraneural thickening, and reach limb flexor digitorum muscles and tendons for pathological changes. Results: 10-wk HRHF rats had higher serum levels of IL-1α, IL-1β and TNFα, than control rats. In the 10-wk HRHF+TM group, IL-1β and TNFα were lower, whereas IL-10 and corticosterone were higher, compared to 10-wk HRHF only rats. Unexpectedly, several voluntary task performance outcomes (grasp force, reach success, and participation) worsened in rats that underwent treadmill running, compared to untreated 10-wk HRHF rats. Examination of forelimb tissues revealed lower cellularity within the flexor digitorum epitendon but higher numbers of CD68+ macrophages within and extraneural fibrosis around median nerves in 10-wk HRHF+TM than 10-wk HRHF rats. Conclusions: Treadmill running was associated with lower systemic inflammation and moderate tendinosis, yet higher median nerve inflammation/fibrosis and worse task performance and sensorimotor behaviors. Continued loading of the injured tissues in addition to stress-related factors associated with forced running/exercise likely contributed to our findings.

Free gait in a shallow pool accelerates recovery after exercise in model mice with fibromyalgia

“…Second, serotonergic neurons may be activated, and serotonin release might be enhanced in the brain ( Otsuka et al, 2016 ; Yoshitake et al, 2004 ); however, the serotonin release may have involved a temporary rather than a continuous elevation after exercise. Third, pain inhibition through training might be diminished due to exercise-induced pain enhancement ( Smith et al, 2020 ; Staud et al, 2005 ). Fourth, we considered the evaluation of pain in this study.…”