Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats

Massicotte, Vicky S.; Frara, Nagat; Harris, Margaret; Amin, Mamta; Wade, Christine K.; Popoff, Steven N.; Barbe, Mary F.

doi:10.1016/j.exger.2015.10.014

Cited by 26 publications

(22 citation statements)

References 80 publications

(106 reference statements)

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“…Task and control rats gained equivalently from 269 ± 4.47 to 327 ± 10.38 grams by the end of the experiment (data not shown), as reported previously in our model [37,38].…”

Section: Weightssupporting

confidence: 87%

High-Speed Treadmill Running Reduces Systemic Inflammation But Fails as a Secondary Intervention For Peripheral Musculoskeletal Discomfort

Paul¹,

Smith²,

Barr-Gillespie³

et al. 2019

Preprint

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Background: Musculoskeletal disorders can result from prolonged repetitive and/or forceful movements. It has been shown that performance of highly repetitive tasks increases serum cytokines, nerve inflammation and sensorimotor declines in a rat model. This study investigated the effectiveness of flat treadmill running in preventing these responses. Methods: Thirteen young adult female Sprague-Dawley rats were trained to perform a high force task for 5 weeks (15 min/day, 5 days/week). All trained rats went on to perform a high repetition, high force reaching and lever-pulling task for 10 weeks (10-week HRHF; 2 hrs/day in four 30 min sessions, 3 days/week). Five task rats were randomly chosen to run on a flat treadmill (TM) for the last 6 weeks of task performance (10-week HRHF+TM; ramping up to 23 m/min, 1hr/day, 5 days/week). Results were compared to 10 control rats. Voluntary task and reflexive sensorimotor behavioral outcomes were assessed and compared. Serum was assayed for inflammatory cytokines, median nerves were assayed for CD68+ macrophages and extraneural thickening, flexor tendons were assayed for any pathological changes. Results: Treadmill running attenuated HRHF task-induced increases in serum TNF-alpha, IL-1beta, CXCL2/MIP2 and IL-10 levels. HRHF task-induced increases in flexor digitorum epitendon cellularity improved with treadmill running. However, several voluntary task performance outcomes, specifically voluntary grasp force, percent successful reaches, and voluntary task participation, worsened with treadmill running. The treadmill intervention failed to rescue HRHF task-induced declines in reflexive grip strength and forepaw mechanical sensitivity, and increases in CD68+ macrophages and extraneural fibrosis within and around median nerves. Conclusions: The treadmill intervention attenuated systemic inflammation and moderate tendinosis, but did not improve task performance or sensorimotor behaviors most likely because this exercise intervention continued to load involved injured forelimbs and worsened median nerve inflammation and fibrosis.

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“…Task and control rats gained equivalently from 269 ± 4.47 to 327 ± 10.38 grams by the end of the experiment (data not shown), as reported previously in our model [37,38].…”

Section: Weightssupporting

confidence: 87%

High-Speed Treadmill Running Reduces Systemic Inflammation But Fails as a Secondary Intervention For Peripheral Musculoskeletal Discomfort

Paul¹,

Smith²,

Barr-Gillespie³

et al. 2019

Preprint

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“…Sixteen custom-designed behavioral apparatuses were used, as previously described [6, 13] and depicted [55]. Briefly, custom-designed force apparati were integrated into standard open field boxes placed into larger sound dampening boxes (Med Associates, St. Albans, VT).…”

Section: Methodsmentioning

confidence: 99%

Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task

et al. 2017

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BackgroundSystemic inflammation is known to induce sickness behaviors, including decreased social interaction and pain. We have reported increased serum inflammatory cytokines in a rat model of repetitive strain injury (rats perform an upper extremity reaching task for prolonged periods). Here, we sought to determine if sickness behaviors are induced in this model and the effectiveness of conservative treatments.MethodsExperimental rats underwent initial training to learn a high force reaching task (10 min/day, 5 days/week for 6 weeks), with or without ibuprofen treatment (TRHF vs. TRHF + IBU rats). Subsets of trained animals went on to perform a high repetition high force (HRHF) task for 6 or 12 weeks (2 h/day, 3 days/week) without treatment, or received two secondary interventions: ibuprofen (HRHF + IBU) or a move to a lower demand low repetition low force task (HRHF-to-LRLF), beginning in task week 5. Mixed-effects models with repeated measures assays were used to assay duration of social interaction, aggression, forepaw withdrawal thresholds and reach performance abilities. One-way and two-way ANOVAs were used to assay tissue responses. Corrections for multiple comparisons were made.ResultsTRHF + IBU rats did not develop behavioral declines or systemic increases in IL-1beta and IL-6, observed in untreated TRHF rats. Untreated HRHF rats showed social interaction declines, difficulties performing the operant task and forepaw mechanical allodynia. Untreated HRHF rats also had increased serum levels of several inflammatory cytokines and chemokines, neuroinflammatory responses (e.g., increased TNFalpha) in the brain, median nerve and spinal cord, and Substance P and neurokinin 1 immunoexpression in the spinal cord. HRHF + IBU and HRHF-to-LRLF rats showed improved social interaction and reduced inflammatory serum, nerve and brain changes. However, neither secondary treatment rescued HRHF-task induced forepaw allodynia, or completely attenuated task performance declines or spinal cord responses.ConclusionsThese results suggest that inflammatory mechanisms induced by prolonged performance of high physical demand tasks mediate the development of social interaction declines and aggression. However, persistent spinal cord sensitization was associated with persistent behavioral indices of discomfort, despite use of conservative secondary interventions indicating the need for prevention or more effective interventions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-017-0354-3) contains supplementary material, which is available to authorized users.

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“…Thus, calcium hydroxyapatite was maintained in the mineralized bone of the stapes ( Fig 5F ). This combination of bone morphometric characteristics is typically indicative of osteoclastic resorptive spaces and vascular profiles, as previously described by Massicotte et al , 2015 [ 39 ].…”

Section: Resultsmentioning

confidence: 61%

Ossicular Bone Damage and Hearing Loss in Rheumatoid Arthritis: A Correlated Functional and High Resolution Morphometric Study in Collagen-Induced Arthritic Mice

Chen¹,

Schwander²,

Barbe³

et al. 2016

PLoS ONE

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Globally, a body of comparative case-control studies suggests that rheumatoid arthritis (RA) patients are more prone to developing hearing loss (HL). However, experimental evidence that supports this hypothesis is still lacking because the human auditory organ is not readily accessible. The aim of this study was to determine the association between bone damage to the ossicles of the middle ear and HL, using a widely accepted murine model of collagen-induced arthritis (RA mice). Diarthrodial joints in the middle ear were examined with microcomputer tomography (microCT), and hearing function was assessed by auditory brainstem response (ABR). RA mice exhibited significantly decreased hearing sensitivity compared to age-matched controls. Additionally, a significant narrowing of the incudostapedial joint space and an increase in the porosity of the stapes were observed. The absolute latencies of all ABR waves were prolonged, but mean interpeak latencies were not statistically different. The observed bone defects in the middle ear that were accompanied by changes in ABR responses were consistent with conductive HL. This combination suggests that conductive impairment is at least part of the etiology of RA-induced HL in a murine model. Whether the inner ear sustains bone erosion or other pathology, and whether the cochlear nerve sustains pathology await subsequent studies. Considering the fact that certain anti-inflammatories are ototoxic in high doses, monitoring RA patients’ auditory function is advisable as part of the effort to ensure their well-being.

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Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats

Cited by 26 publications

References 80 publications

High-Speed Treadmill Running Reduces Systemic Inflammation But Fails as a Secondary Intervention For Peripheral Musculoskeletal Discomfort

High-Speed Treadmill Running Reduces Systemic Inflammation But Fails as a Secondary Intervention For Peripheral Musculoskeletal Discomfort

Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task

Ossicular Bone Damage and Hearing Loss in Rheumatoid Arthritis: A Correlated Functional and High Resolution Morphometric Study in Collagen-Induced Arthritic Mice

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