Repetitive, Negligible Force Reaching in Rats Induces Pathological Overloading of Upper Extremity Bones

Abstract

Work-related repetitive motion disorders are costly. Immunohistochemical changes in bones resulting from repetitive reaching and grasping in 17 rats were examined. After 3-6 weeks, numbers of ED1 ؉ macrophages and osteoclasts increased at periosteal surfaces of sites of muscle and interosseous membrane attachment and metaphyses of reach and nonreach forelimbs. These findings indicate pathological overloading leading to inflammation and subsequent bone resorption.Introduction: Sixty-five percent of all occupational illnesses in U.S. private industry are attributed to musculoskeletal disorders arising from the performance of repeated motion, yet the precise mechanisms of tissue pathophysiology have yet to be determined for work-related musculoskeletal disorders. This study investigates changes in upper extremity bone tissues resulting from performance of a voluntary highly repetitive, negligible force reaching and grasping task in rats. Materials and Methods: Seventeen rats reached an average of 8.3 times/minute for 45-mg food pellets for 2 h/day, 3 days/week for up to 12 weeks. Seven rats served as normal or trained controls. Radius, ulna, humerus, and scapula were collected bilaterally as follows: radius and ulna at 0, 3, 4, 5, 6, and 12 weeks and humerus and scapula at 0, 4, and 6 weeks. Bones were examined for ED1-immunoreactive mononuclear cells and osteoclasts. Double-labeling immunohistochemistry was performed for ED1 (monocyte/macrophage lineage cell marker) and TRACP (osteoclast marker) to confirm that ED1 ϩ multinucleated cells were osteoclasts. Differences in the number of ED1 ϩ cells over time were analyzed by ANOVA. Results: Between 3 and 6 weeks of task performance, the number of ED1 ϩ mononuclear cells and osteoclasts increased significantly at the periosteal surfaces of the distal radius and ulna of the reach and nonreach limbs compared with control rats. These cells also increased at periosteal surfaces of humerus and scapula of both forelimbs by 4 -6 weeks. These cellular increases were greatest at muscle attachments and metaphyseal regions, but they were also present at some interosseous membrane attachments. The number of ED1 ϩ cells decreased to control levels in radius and ulna by 12 weeks. Conclusions: Increases in ED1ϩ mononuclear cells and osteoclasts indicate that highly repetitive, negligible force reaching causes pathological overloading of bone leading to inflammation and osteolysis of periosteal bone tissues.

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

“…This resulted in an actual reach rate of 8.27 reaches/min ± 4.11 SD . Further details of the training apparatus are described in Barbe et al (2003), Barr et al (2003) and Clark et al (2003).…”

“…Our laboratory has investigated the pathophysiology of repetitive motion injuries of the upper limb caused by voluntary high repetition tasks, with or without force Barr et al, 2003Clark et al, 2003Clark et al, , 2004. Using a novel rat model, we found that repetitive reaching and grasping causes a marked and widespread increase in recruited macrophages in musculotendinous and skeletal tissues as well as in the median nerve at the level of the carpal tunnel.…”

Serum and tissue cytokines and chemokines increase with repetitive upper extremity tasks

“…In serum, we chose 11 cyotokines and chemokines to examine, including key pro-inflammatory cytokines (IL-1a/b and TNFa), a highly pleiotropic cytokines with both pro-and anti-inflammatory properties (IL-6), a potent anti-inflammatory cytokine (IL-10), several inflammatory chemokines known to mediate chemotaxis of monocytes/macrophages and T cells (RANTES, macrophage inflammatory protein 3 and 2a, interferon gamma and fractalkine), and a chemokine that mediates chemotaxis of neutrophils and growth of fibroblasts (growth-related oncogene keratinocytederived cytokine). We examine macrophage infiltration into flexor forelimb tissues of LRNF rats to add to results from our previous studies of HRNF rats 2,3,7,9 and correlate their numbers with serum levels of inflammatory cytokines and chemokines. In addition, we compare performance parameters, reach rate, and grip strength, with the inflammatory response.…”

“…[2][3][4]7,9 The macrophage response is associated with increased inflammatory cytokines in the median nerve, 9 and increased serum IL-1a following HRNF task performance. 2 A variety of inflammatory mediators including cytokines and chemokines are released by injured cells and infiltrating macrophages.…”

“…Recent work suggests that RMIs induce injury in several tissue types in animal models, [1][2][3][4][5][6] as well as an early inflammatory response at the tissue level. 2,3,[7][8][9] Increases in four circulating inflammatory mediators, C-reactive protein, interleukin 1 beta (IL-1b), IL-6, and tumor necrosis factor alpha (TNFa) have also been shown to increase in patients with upper extremity overuse disorders. 10 The factors triggering underlying pathophysiological responses are still under investigation, which impedes progress toward their primary and secondary prevention.…”