Systematic review of biochemical biomarkers for neck and upper-extremity musculoskeletal disorders

Gold, Judith E.; Hallman, David; Hellström, Fredrik; Björklund, Martin; Crenshaw, Albert G.; Djupsjöbacka, Mats; Heiden, Marina; Mathiassen, Svend Erik; Piligian, George; Barbe, Mary F.

doi:10.5271/sjweh.3533

Cited by 24 publications

(26 citation statements)

References 75 publications

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“…Chronic overuse‐induced musculoskeletal disorders are also known as work‐related musculoskeletal disorders, repetitive motion disorders, and repetitive strain injuries. They include diagnoses of carpal tunnel syndrome, tendinopathies, and myalgias . Risk factors include chronic performance of high repetition and high force activities .…”

mentioning

confidence: 99%

“…We have a clinically relevant rodent model of chronic overuse in which rats perform an operant reaching, grasping and lever‐pulling task for food reward . Performance of this task at high repetition high force (HRHF) levels for 3–18 weeks induces progressive musculotendinous and nerve fibrosis and sensorimotor declines, similar to responses seen in patients with upper extremity overuse‐induced musculoskeletal disorders . Use of ibuprofen or anti‐tumor necrosis factor ɑ drug reduced tissue inflammation in this model .…”

mentioning

confidence: 99%

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Blocking CCN2 Reduces Progression of Sensorimotor Declines and Fibrosis in a Rat Model of Chronic Repetitive Overuse

Barbe

Hilliard

Delany

et al. 2019

Journal Orthopaedic Research

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Fibrosis may be a key factor in sensorimotor dysfunction in patients with chronic overuse‐induced musculoskeletal disorders. Using a clinically relevant rodent model, in which performance of a high demand handle‐pulling task induces tissue fibrosis and sensorimotor declines, we pharmacologically blocked cellular communication network factor 2 (CCN2; connective tissue growth factor) with the goal of reducing the progression of these changes. Young adult, female Sprague–Dawley rats were shaped to learn to pull at high force levels (10 min/day, 5 weeks), before performing a high repetition high force (HRHF) task for 3 weeks (2 h/day, 3 days/week). HRHF rats were untreated, or treated in task weeks 2 and 3 with a monoclonal antibody that blocks CCN2 (FG‐3019), or a control immunoglobulin G (IgG). Control rats were untreated or received FG‐3019, IgG, or vehicle (saline) injections. Mean task reach rate and grasp force were higher in 3‐week HRHF + FG‐3019 rats, compared with untreated HRHF rats. Grip strength declined while forepaw mechanical sensitivity increased in untreated HRHF rats, compared with controls; changes improved by FG‐3019 treatment. The HRHF task increased collagen in multiple tissues (flexor digitorum muscles, nerves, and forepaw dermis), which was reduced with FG‐3019 treatment. FG‐3019 treatment also reduced HRHF‐induced increases in CCN2 and transforming growth factor β in muscles. In tendons, FG‐3019 reduced HRHF‐induced increases in CCN2, epitendon thickening, and cell proliferation. Our findings indicate that CCN2 is critical to the progression of chronic overuse‐induced multi‐tissue fibrosis and functional declines. FG‐3019 treatment may be a novel therapeutic strategy for overuse‐induced musculoskeletal disorders. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2004–2018, 2019

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confidence: 99%

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confidence: 99%

Blocking CCN2 Reduces Progression of Sensorimotor Declines and Fibrosis in a Rat Model of Chronic Repetitive Overuse

Barbe

Hilliard

Delany

et al. 2019

Journal Orthopaedic Research

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“…These substance concentrations correlate with pain intensity and are associated with muscle cell damage and necrosis (55). The findings of an elevated level of serotonin in the myalgic muscle are supported by a recent review on biochemical biomarkers (31). …”

Section: Pa As Cause Of Pain Development and Msdmentioning

confidence: 72%

“…Physical exercise training in sports targets strength, aerobic power, and coordination and shows efficacy on improved performance associated with changes in physical capacity. As has been pointed out in a recent review (31), much less is known about a possible pain-reducing effect of physical exercise training and the morphological and biochemical mechanisms underlying a reduction in pain.…”

Section: Pa As Cure For Muscular Pain and Health Enhancementmentioning

confidence: 99%

Physical Activity as Cause and Cure of Muscular Pain: Evidence of Underlying Mechanisms

Søgaard

Sjøgaard

2017

Exercise and Sport Sciences Reviews

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“…Treatment of work and repetitive strain injury related MSDs remains challenging because the pathological processes are not fully understood, are complex and involve many biopsychosocial factors [6][7][8]. It is generally understood that micro-trauma of the tissues heal quickly (i.e., during the subacute phase) unless inflammation is enhanced and/or imbalanced (pro-vs. anti-inflammatory agents), exacerbating tissue damage and fibrosis [9,10].…”

Section: Introductionmentioning

confidence: 99%

Forced treadmill running reduces systemic inflammation yet worsens upper limb discomfort in a rat model of work-related musculoskeletal disorders

Smith

Barr-Gillespie

Klyne

et al. 2020

BMC Musculoskelet Disord

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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.

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Systematic review of biochemical biomarkers for neck and upper-extremity musculoskeletal disorders

Cited by 24 publications

References 75 publications

Blocking CCN2 Reduces Progression of Sensorimotor Declines and Fibrosis in a Rat Model of Chronic Repetitive Overuse

Blocking CCN2 Reduces Progression of Sensorimotor Declines and Fibrosis in a Rat Model of Chronic Repetitive Overuse

Physical Activity as Cause and Cure of Muscular Pain: Evidence of Underlying Mechanisms

Forced treadmill running reduces systemic inflammation yet worsens upper limb discomfort in a rat model of work-related musculoskeletal disorders

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