Peripheral neuritis and increased spinal cord neurochemicals are induced in a model of repetitive motion injury with low force and repetition exposure.

Performance of high repetition tasks with or without force is associated with peripheral tissue inflammation, decreased nerve function and motor dysfunction. Here, we examined whether a low repetition task with negligible force (LRNF) produces fewer tissue and behavioral pathologies than previously observed with high repetition tasks using our rat model of repetitive motion injury (RMI). Thirty-seven rats were randomized into control or LRNF groups, the latter reaching and grasping a 45 mg food pellet at a rate of 3 reaches/min. This task was performed in 4, 0.5 5 h sessions with 1.5 5 h rest periods for 3 days/week for up to 12 weeks. Examination of distal median nerve, forelimb flexor tendons and bones for ED1-positive cells (macrophages and osteoclasts) revealed increases in nerve and bone in week 12. The nerve also contained increased TNF-alpha expressing cells in week 12. Examination of spinal cord dorsal horns revealed increased immunoexpression of Substance P in week 8 and neurokinin-1 in weeks 8 and 12 in the superficial lamina. Motor behavioral analyses showed no changes in reach rate across weeks, slightly reduced task duration (a measurement of voluntary task participation) in week 12, but significantly increased extra arm movement reversals during reaching in week 8. These extra movement reversals were corrections for missed food pellets during a reach. Thus, performance of even a low repetition, negligible force upper extremity task for 3 months can induce mild peripheral tissue inflammation, neurochemical increases in spinal cord dorsal horns, and declines in fine motor control.

Increase in inflammatory cytokines in median nerves in a rat model of repetitive motion injury.

We examined cytokines in rat median nerves following performance of a high repetition reaching and grasping task at a rate of 8 reaches/min for up to 8 weeks. IL-1alpha, IL-1beta, TNF-alpha, IL-6 and IL-10 were analyzed by immunohistochemistry. Double-labeling immunohistochemistry for ED1, a marker of phagocytic macrophages, was also performed. We found increased immunoexpression of IL-6 by week 3, increases in all 5 cytokines by week 5. This response was transient as all cytokines returned to control levels by 8 weeks of performance of a high repetition negligible force task. Cytokine sources included Schwann cells, fibroblasts and phagocytic macrophages (ED1-immunopositive). These findings suggest that cytokines are involved in the pathophysiology of repetitive motion injuries in peripheral nerves.

Performance of a high-repetition, high-force task induces carpal tunnel syndrome in rats.

STUDY DESIGN: A randomized controlled prospective experimental study with some repeated measures. OBJECTIVES: To characterize behavioral, sensory, motor, and nerve conduction decrements, and histological changes in the median nerve in rats trained to perform a high-force repetitive task. BACKGROUND: Understanding of work-related carpal tunnel syndrome is hampered by the lack of experimental studies of the causes and mechanisms of nerve compression induced by repetitive motion. Most animal models of nerve compression have not employed voluntary repetitive motion as the stimulus for pathophysiological changes. METHODS AND MEASURES: Thirty Sprague-Dawley rats served as controls for 1 or more studies. Ten rats were trained to pull on a bar with 60% maximum force 4 times per minute, 2 h/d, 3 d/wk for 12 weeks. Motor behavior and limb withdrawal threshold force were characterized weekly. Grip strength and median nerve conduction velocity were measured after 12 weeks. Median nerves were examined immunohistochemically for ED1-positive macrophages, collagen, and connective tissue growth factor. RESULTS: Reach rate and duration of task performance declined over 12 weeks. Grip strength and nerve conduction velocity were significantly lower after 12 weeks than in controls. Limb withdrawal threshold increased between weeks 6 and 12. Median nerves at the level of the wrist showed increases in macrophages, collagen, and connective-tissue growth-factor-positive cells. These effects were seen in both the reach and nonreach limbs. CONCLUSIONS: This animal model exhibits all the features of human carpal tunnel syndrome, including impaired sensation, motor weakness, and decreased median nerve conduction velocity. It establishes a causal relationship between performance of a repetitive task and development of carpal tunnel syndrome.

Median nerve trauma in a rat model of work-related musculoskeletal disorder.

Anatomical and physiological changes were evaluated in the median nerves of rats trained to perform repetitive reaching. Motor degradation was evident after 4 weeks. ED1-immunoreactive macrophages were seen in the transcarpal region of the median nerve of both forelimbs by 5-6 weeks. Fibrosis, characterized by increased immunoexpression of collagen type I by 8 weeks and connective tissue growth factor by 12 weeks, was evident. The conduction velocity (NCV) within the carpal tunnel showed a modest but significant decline after 9-12 weeks. The lowest NCV values were found in animals that refused to participate in the task for the full time available. Thus, both anatomical and physiological signs of progressive tissue damage were present in this model. These results, together with other recent findings indicate that work-related carpal tunnel syndrome develops through mechanisms that include injury, inflammation, fibrosis and subsequent nerve compression.