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 h/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 h/day, 5 days/wk). Results were compared to 10 control rats and 6 rats that underwent 6 weeks of treadmill running following training only (TRthen-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.

Key indicators of repetitive overuse-induced neuromuscular inflammation and fibrosis are prevented by manual therapy in a rat model

“…Since we have previously shown that prolonged performance of high intensity repetitive tasks induce pathological changes in flexor digitorum tendons [ 15 , 52 ], we next examined for such changes in this study. We first examined for changes in mid- to distal flexor digitorum tendon proper (interior) regions and saw more rounded cells and moderately enhanced cellularity and collagen fibril disorganization in TASK-Ac tendons, relative to the other groups (Fig.…”

“…Pro-inflammatory processes are required for proper muscle repair and clearance of injury-induced debris [ 54 – 56 ]. In this model, CD68+ macrophages and pro-inflammatory cytokines elevate in upper extremity nerves, muscles and tendons either immediately after the initial training period (task week 0) during which rats ramp up from naïve to high force lever pulling, or by task week 3 [ 7 , 10 , 12 , 40 , 52 ]. The post-training task week 0 is also the peak production point of several pro-inflammatory cytokines (such as, muscle CCL2/MCP-1 and IL-18), while task weeks 3 to 6 are the peaks for others (such as, muscle and serum TNF-α) [ 7 , 10 , 19 ].…”

“…8 b), similar to our past short- and long-term studies examining the effects of preventive manual therapy on motor behaviors [ 12 , 13 ]. Reflexive grip strength is a complex neuromuscular behavior that can decline in response to enhanced median compressive neuropathy, nerve or intramuscular inflammatory responses, or muscle fibrosis [ 14 , 35 , 48 , 49 , 52 , 82 ]. Such declines can be prevented with early administration of anti-inflammatory drugs, such as administration of diclofenac sodium within 3 days of exercise-induced muscle damage [ 83 ] or the anti-CCN2 drug mentioned earlier [ 40 ].…”

Occupational shoulder disability: functional recovery after decompression and neurolysis of the upper brachial plexus and the long thoracic nerve

“…released directly from the involved skeletal muscle(s) and tendon(s) or the surrounding fascial tissues, causing tissue damage and fibrosis [25]. Enhanced intraneural inflammation and nerve fibrosis were shown in the high-repetition high-force treadmill group compared to the control group [26]. It was also shown to correlate with increasing pain and tingling.…”

Does the Interaction between Local and Systemic Inflammation Provide a Link from Psychology and Lifestyle to Tissue Health in Musculoskeletal Conditions?

“…Although the anti-inflammatory effects of exercise are largely systemic and attributed to changes in “non-muscle” factors/cells (e.g., reduced adipose tissue, macrophages, T- and NK cells and activation of the HPA axis) [ 210 , 211 ], the contracting muscle cells themselves produce IL-6, which inhibits TNF and stimulates the production of anti-inflammatory cytokines [ 212 ]—highlighting the dual systemic and local impact of exercise on inflammation, with potentially broad therapeutic implications. For instance, the potent anti-inflammatory effects of aerobic whole-body exercise [ 191 , 213 ] are accompanied by reduced musculoskeletal fibrosis [ 27 ] (unless injured tissues are loaded [ 214 ]) and improvements in psychological wellbeing and lifestyle health [ 215 , 216 ]. Other factors might have similar multidirectional effects.…”