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

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 (TR-then-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-1ß and TNFα, than control rats. In the 10-wk HRHF+TM group, IL-1ß 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.

Frontal plane knee and hip kinematics during sit-to-stand and proximal lower extremity strength in persons with patellofemoral osteoarthritis: a pilot study.

Increased joint stress and malalignment are etiologic factors in osteoarthritis. Static tibiofemoral frontal plane malalignment is associated with patellofemoral osteoarthritis (PFOA). Patellofemoral joint stress is increased by activities such as sit-to-stand (STS); this stress may be even greater if dynamic frontal plane tibiofemoral malalignment occurs. If hip muscle or quadriceps weakness is present in persons with PFOA, aberrant tibiofemoral frontal plane movement may occur, with increased patellofemoral stress. No studies have investigated frontal plane tibiofemoral and hip kinematics during STS in persons with PFOA or the relationship of hip muscle and quadriceps strength to these motions. Eight PFOA and seven control subjects performed STS from a stool during three-dimensional motion capture. Hip muscle and quadriceps strength were measured as peak isometric force. The PFOA group demonstrated increased peak tibial abduction angles during STS, and decreased hip abductor, hip extensor, and quadriceps peak force versus controls. A moderate inverse relationship between peak tibial abduction angle and peak hip abductor force was present. No difference between groups was found for peak hip adduction angle or peak hip external rotator force. Dynamic tibiofemoral malalignment and proximal lower extremity weakness may cause increased patellofemoral stress and may contribute to PFOA incidence or progression.

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

BACKGROUND: We 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). METHODS: Rats 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. RESULTS: Several 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. CONCLUSIONS: Although 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.

Ergonomic task reduction prevents bone osteopenia in a rat model of upper extremity overuse.

We evaluated the effectiveness of ergonomic workload reduction of switching rats from a high repetition high force (HRHF) lever pulling task to a reduced force and reach rate task for preventing task-induced osteopenic changes in distal forelimb bones. Distal radius and ulna trabecular structure was examined in young adult rats performing one of three handle-pulling tasks for 12 wk: (1) HRHF, (2) low repetition low force (LRLF); or (3) HRHF for 4 wk and than LRLF thereafter (HRHF-to-LRLF). Results were compared to age-matched controls rats. Distal forelimb bones of 12-wk HRHF rats showed increased trabecular resorption and decreased volume, as control rats. HRHF-to-LRLF rats had similar trabecular bone quality as control rats; and decreased bone resorption (decreased trabecular bone volume and serum CTX1), increased bone formation (increased mineral apposition, bone formation rate, and serum osteocalcin), and decreased osteoclasts and inflammatory cytokines, than HRHF rats. Thus, an ergonomic intervention of HRHF-to-LRLF prevented loss of trabecular bone volume occurring with prolonged performance of a repetitive upper extremity task. These findings support the idea of reduced workload as an effective approach to management of work-related musculoskeletal disorders, and begin to define reach rate and load level boundaries for such interventions.

Physical performance measurement in persons with patellofemoral osteoarthritis: A pilot study.

BACKGROUND: Patellofemoral osteoarthritis (PFOA) is associated with pain and decreased self-reported function. The impact of PFOA on actual physical performance is currently unknown. OBJECTIVE: To investigate the impact of PFOA on physical performance and pain. METHODS: Eight participants aged 40-65 years with bilateral, symptomatic, radiographic PFOA and 7 age- and gender-matched pain-free control participants without radiographic PFOA were studied. Physical performance was measured with the Timed-Up-and-Go (TUG) and 50-foot Fast-Paced-Walk (FPW) tests. Dependent variables included time to complete the TUG and FPW; pretest-posttest change in pain intensity (TUG and FPW); and self-reports of perceived knee pain, stiffness, and physical function. Data were analyzed with nonparametric statistics. RESULTS: The PFOA group TUG time was longer than the control group (p=0.01). No difference between groups was found for FPW time. Pretest-posttest pain increased for the TUG and FPW in PFOA participants (p< 0.05). The PFOA group reported greater knee pain, stiffness, and less physical function than controls (previous 48 hours) (p < 0.01). CONCLUSIONS: Symptomatic, radiographic PFOA is associated with increased pain during the TUG and FPW tests and longer time required to complete the TUG. The TUG may be a more sensitive test of physical performance in PFOA.

The effects of aging on the attentional demands of walking toward and stepping up onto a curb.

Community ambulation requires the capacity to alter gait in response to obstacles within the path of travel that appear at a known location. Acquiring information from the environment to safely negotiate a curb may increase the cognitive demands of walking. The purpose of this study was to examine the attentional demands of walking toward and stepping up onto a curb in young, middle-age and older adults. Single and dual-task voice reaction time (VRT) was measured in community-dwelling young (n = 24), middle-age (n = 24), and older adults (n = 24) across 5 conditions: sitting in a chair, standing, level walking, and walking toward and while stepping up onto a curb. A 3 (group) by 5 (task condition) ANOVA was used to examine VRT. The interaction of group with task revealed statistically significant within group increases in VRT when comparing either sitting and/or standing to walking on a level surface and walking toward the curb and stepping up onto the curb. When compared to the other groups, older adults had significantly longer VRT for all walking tasks. Stepping onto the curb significantly increased the attentional requirements of walking for all of the groups when compared to level walking. The pattern of statistically significant between group and within group differences during the walking tasks indicate the effects of a curb located at a predictable place in the environment on attentional allocation.

Increased serum and musculotendinous fibrogenic proteins following persistent low-grade inflammation in a rat model of long-term upper extremity overuse.

We examined the relationship between grip strength declines and muscle-tendon responses induced by long-term performance of a high-repetition, low-force (HRLF) reaching task in rats. We hypothesized that grip strength declines would correlate with inflammation, fibrosis and degradation in flexor digitorum muscles and tendons. Grip strength declined after training, and further in weeks 18 and 24, in reach limbs of HRLF rats. Flexor digitorum tissues of reach limbs showed low-grade increases in inflammatory cytokines: IL-1ß after training and in week 18, IL-1α in week 18, TNF-α and IL-6 after training and in week 24, and IL-10 in week 24, with greater increases in tendons than muscles. Similar cytokine increases were detected in serum with HRLF: IL-1α and IL-10 in week 18, and TNF-α and IL-6 in week 24. Grip strength correlated inversely with IL-6 in muscles, tendons and serum, and TNF-α in muscles and serum. Four fibrogenic proteins, TGFB1, CTGF, PDGFab and PDGFbb, and hydroxyproline, a marker of collagen synthesis, increased in serum in HRLF weeks 18 or 24, concomitant with epitendon thickening, increased muscle and tendon TGFB1 and CTGF. A collagenolytic gelatinase, MMP2, increased by week 18 in serum, tendons and muscles of HRLF rats. Grip strength correlated inversely with TGFB1 in muscles, tendons and serum; with CTGF-immunoreactive fibroblasts in tendons; and with MMP2 in tendons and serum. Thus, motor declines correlated with low-grade systemic and musculotendinous inflammation throughout task performance, and increased fibrogenic and degradative proteins with prolonged task performance. Serum TNF-α, IL-6, TGFB1, CTGF and MMP2 may serve as serum biomarkers of work-related musculoskeletal disorders, although further studies in humans are needed.

Aging contributes to inflammation in upper extremity tendons and declines in forelimb agility in a rat model of upper extremity overuse.

We sought to determine if tendon inflammatory and histopathological responses increase in aged rats compared to young rats performing a voluntary upper extremity repetitive task, and if these changes are associated with motor declines. Ninety-six female Sprague-Dawley rats were used in the rat model of upper extremity overuse: 67 aged and 29 young adult rats. After a training period of 4 weeks, task rats performed a voluntary high repetition low force (HRLF) handle-pulling task for 2 hrs/day, 3 days/wk for up to 12 weeks. Upper extremity motor function was assessed, as were inflammatory and histomorphological changes in flexor digitorum and supraspinatus tendons. The percentage of successful reaches improved in young adult HRLF rats, but not in aged HRLF rats. Forelimb agility decreased transiently in young adult HRLF rats, but persistently in aged HRLF rats. HRLF task performance for 12 weeks lead to increased IL-1beta and IL-6 in flexor digitorum tendons of aged HRLF rats, compared to aged normal control (NC) as well as young adult HRLF rats. In contrast, TNF-alpha increased more in flexor digitorum tendons of young adult 12-week HRLF rats than in aged HRLF rats. Vascularity and collagen fibril organization were not affected by task performance in flexor digitorum tendons of either age group, although cellularity increased in both. By week 12 of HRLF task performance, vascularity and cellularity increased in the supraspinatus tendons of only aged rats. The increased cellularity was due to increased macrophages and connective tissue growth factor (CTGF)-immunoreactive fibroblasts in the peritendon. In conclusion, aged rat tendons were overall more affected by the HRLF task than young adult tendons, particularly supraspinatus tendons. Greater inflammatory changes in aged HRLF rat tendons were observed, increases associated temporally with decreased forelimb agility and lack of improvement in task success.