The presence of physiological stress shielding in the degenerative cycle of musculoskeletal disorders

Driscoll, Mark; Blyum, Leonid

doi:10.1016/j.jbmt.2010.05.002

Cited by 33 publications

(21 citation statements)

References 33 publications

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“…Sensorimotor behavioral declines in untreated HRHF rats suggest they have either discomfort or reduced tissue function. Fibrosis within and around tissues can reduce dynamic tissue biomechanical function (muscle fibrosis can biomechanically reduce muscle contractions). Improved reach rate, voluntary grasp force and reflexive grip strength with FG‐3019 treatment could be due to the reduced tissue collagen, an idea supported by the inverse relationship between motor function and tissue collagen.…”

Section: Discussionmentioning

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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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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Section: Discussionmentioning

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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“…It has been postulated that fibrosis in and around muscles and nerves may distort dynamic biomechanical properties and increase tissue strain due to adherence to adjacent structures, reducing dynamic tissue function (Driscoll and Blyum 2011). Fibrosis in the connective tissue “container” surrounding nerves has been linked to chronic nerve inflammation (Bove, Weissner et al 2009) and compression (O’Brien, Mackinnon et al 1987), which are known to increase pain behaviors (as a consequence of compressive nerve irritation), evoke ectopic mechanical sensitivity and ongoing activity in nociceptor axons (Bove, Ransil et al 2003, Bove 2009), and decrease grip strength (due to reduced nerve conduction).…”

Section: Discussionmentioning

confidence: 99%

Manual therapy as an effective treatment for fibrosis in a rat model of upper extremity overuse injury

Bove

Harris

Zhao

et al. 2016

Journal of the Neurological Sciences

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Key clinical features of carpal tunnel syndrome and other types of cumulative trauma disorders of the hand and wrist include pain and functional disabilities. Mechanistic details remain under investigation but may involve tissue inflammation and/or fibrosis. We examined the effectiveness of modeled manual therapy (MMT) as a treatment for sensorimotor behavior declines and increased fibrogenic processes occurring in forearm tissues of rats performing an high repetition high force (HRHF) reaching and grasping task for 12 weeks. Young adult, female rats were examined: food restricted control rats (FRC, n=12); rats that were trained for 6 weeks before performing the HRHF task for 12 weeks with no treatment (HRHF-CON, n=11); and HRHF task rats received modeled manual therapy (HRHF-MMT, n=5) for 5 days/week for the duration of the 12-week of task. Rats receiving the MMT expressed fewer discomfort-related behaviors, and performed progressively better in the HRHF task. Grip strength, while decreased after training, improved following MMT. Fibrotic nerve and connective tissue changes (increased collagen and TGF-β1 deposition) present in 12-week HRHF-CON rats were significantly decreased in 12-week HRHF-MMT rats. These observations support the investigation of manual therapy as a preventative for repetitive motion disorders.

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“…Furthermore, the fibrotic changes, evident as increased collagen matrix (i.e. fascia) within and surrounding muscles, tendons and nerves (see Figure 6A and references [22,55-58]) may distort dynamic biomechanical properties and increase tissue strain due to adherence to adjacent structures, as postulated by Driscoll and Blyum [103]. …”

Section: Discussionmentioning

confidence: 99%

The interaction of force and repetition on musculoskeletal and neural tissue responses and sensorimotor behavior in a rat model of work-related musculoskeletal disorders

Barbe

Gallagher

Massicotte

et al. 2013

BMC Musculoskelet Disord

117

178

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BackgroundWe examined the relationship of musculoskeletal risk factors underlying force and repetition on tissue responses in an operant rat model of repetitive reaching and pulling, and if force x repetition interactions were present, indicative of a fatigue failure process. We examined exposure-dependent changes in biochemical, morphological and sensorimotor responses occurring with repeated performance of a handle-pulling task for 12 weeks at one of four repetition and force levels: 1) low repetition with low force, 2) high repetition with low force, 3) low repetition with high force, and 4) high repetition with high force (HRHF).MethodsRats underwent initial training for 4–6 weeks, and then performed one of the tasks for 12 weeks, 2 hours/day, 3 days/week. Reflexive grip strength and sensitivity to touch were assayed as functional outcomes. Flexor digitorum muscles and tendons, forelimb bones, and serum were assayed using ELISA for indicators of inflammation, tissue stress and repair, and bone turnover. Histomorphometry was used to assay macrophage infiltration of tissues, spinal cord substance P changes, and tissue adaptative or degradative changes. MicroCT was used to assay bones for changes in bone quality.ResultsSeveral force x repetition interactions were observed for: muscle IL-1alpha and bone IL-1beta; serum TNFalpha, IL-1alpha, and IL-1beta; muscle HSP72, a tissue stress and repair protein; histomorphological evidence of tendon and cartilage degradation; serum biomarkers of bone degradation (CTXI) and bone formation (osteocalcin); and morphological evidence of bone adaptation versus resorption. In most cases, performance of the HRHF task induced the greatest tissue degenerative changes, while performance of moderate level tasks induced bone adaptation and a suggestion of muscle adaptation. Both high force tasks induced median nerve macrophage infiltration, spinal cord sensitization (increased substance P), grip strength declines and forepaw mechanical allodynia by task week 12.ConclusionsAlthough not consistent in all tissues, we found several significant interactions between the critical musculoskeletal risk factors of force and repetition, consistent with a fatigue failure process in musculoskeletal tissues. Prolonged performance of HRHF tasks exhibited significantly increased risk for musculoskeletal disorders, while performance of moderate level tasks exhibited adaptation to task demands.

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The presence of physiological stress shielding in the degenerative cycle of musculoskeletal disorders

Cited by 33 publications

References 33 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

Manual therapy as an effective treatment for fibrosis in a rat model of upper extremity overuse injury

The interaction of force and repetition on musculoskeletal and neural tissue responses and sensorimotor behavior in a rat model of work-related musculoskeletal disorders

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