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

Abstract

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-1α, IL-1β, TNF-α, 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.

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

“…Tissues were prepared, immunostained, and quantified as described previously. 2,7,9 Statistical Analyses To test for differences in serum cytokines/chemokines between the 3 control groups, a one-way ANOVA was performed for each cytokine/chemokine. Because there were no differences between the three control groups (see Results section), all control rats were combined into one group.…”

“…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.…”

“…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.…”

“…[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.…”

“…2 A variety of inflammatory mediators including cytokines and chemokines are released by injured cells and infiltrating macrophages. 9,11 Although serum cytokine and chemokine response patterns to exercise of varying intensities [12][13][14][15] and multiple organ trauma and fractures have been studied, [16][17][18] exposure to more chronic, lower levels of injury are not yet well characterized.…”