Functional Response to Pain and its Treatment in Knee Osteoarthritis

Osteoarthritis (OA) is one of the most common sources of musculoskeletal pain. It is generally accepted that in response to a painful stimulus there will be a modification in movement to reduce or avoid this pain. There are very few studies looking at the potential for pain treatment to change movement mechanics in OA. Yet this information is important as the functional response to OA pain treatment can alter the mechanical environment of the joint and thus may impact the efficacy of treatment. Our recent work has shown a sensitivity of joint loading measures to repeated pain treatment washouts and to the mechanism of action of the pain treatment. However, there remains a paucity of information relating kinematic coordination and variability of movement to pain modifications. A single-blind washout, double-blind treatment, double-dummy cross-over pilot study using placebo, Oxycodone and Celecoxib was used to test the hypothesis primary and secondary movements of the knee are significantly different for the two active drug treatments compared to a double blind placebo treatment. Walking kinematics data were collected at self-selected normal pace at the beginning of each arm of the cross-over study design. Significant differences between Placebo and Celecoxib arms were found for the mean internal-external knee rotation angle(

Examining Movement Function in Patients with Knee Osteoarthritis

As part of the mini-symposium entitled Biomechanical Gait Analysis for Improving Clinical Outcomes: Applications for Orthopedics, Geriatrics and Community Based Research, this presentation explores research on gait analysis and pain for patients with knee osteoarthritis

Older women’s muscle and gait response to a bout of exercise differs by physical activity level

Changes in gait are a consequence of aging and likely contribute to knee osteoarthritis (OA) incidence. Decrements in muscle function with age, including muscle power and fatigue resistance, may contribute to changes in gait and, subsequently, knee OA. Examining the impact of habitual physical activity (PA) on gait mechanics and muscle function may provide insight for interventions to modify knee OA risk. As knee OA affects women at greater rates than men, the current study focused on older women. The aim of this study was to determine if older women with different levels of habitual PA experienced the same effect, in terms of muscle function and gait biomechanics, in response to 30 minutes of treadmill walking (30MTW). We hypothesized that sedentary women (SED) would display greater decreases in knee extensor strength and power and larger changes in gait biomechanics compared to highly active women (ACT). Twelve women (6 SED, 6 ACT) aged 61.3±3.9 years with BMI 22.3±2.2 participated in this study. Gait mechanics and knee extensor strength and power were collected pre- and post-30MTW. Unpaired t-tests were used to compare changes in knee extensor function and gait mechanics between SED and ACT with significance set at p\u3c0.1. In response to the 30MTW, there was a larger decrease in high-velocity knee extensor power for SED vs. ACT (-26.3±12.2 vs. -12.9±13.7%). In addition, SED compared to ACT had a larger increase in sagittal hip range of motion during stance (+1.9±2.5 vs. +0.3±0.7°), a larger increase in dorsiflexion at heel strike (+2.2±1.7 vs. +0.3±2.3°), a larger decrease in plantarflexion at toe-off (-1.6±2.5 vs. +0.9±1.9°), and a larger decrease in anterior position of the femur relative to the tibia during loading response (-2.6±4.0 vs. +0.5±2.9 mm). These findings suggest PA level may affect biomechanical health in older women, especially with regard to exercise-induced fatigue

Gait mechanics contribute to exercise induced pain flares in knee osteoarthritis

Background Exercise-induced pain flares represent a significant barrier for individuals with knee osteoarthritis to meet physical activity recommendations. There is a need to understand factors that contribute to pain flares and the potential for the motor system to adapt and reduce joint loading should a flare occur. The study aim was to examine the impact of a bout of exercise on self-reported pain, walking mechanics and muscle co-contraction for participants with knee osteoarthritis. Methods Thirty-six adults (17 healthy older and 19 knee osteoarthritis) participated in this study. Self-reported pain, joint mechanics and muscle co-activation during gait at two self-selected speeds were collected before and after a 20-min preferred pace treadmill walk (20MTW). Results Eight of nineteen osteoarthritis participants had a clinically significant pain flare response to the 20MTW. At baseline the participants that did not experience a pain flare had smaller knee flexion and total reaction moments compared to both the participants with pain flares (p = 0.02; p = 0.05) and controls (p \u3c 0.001; p \u3c 0.001). In addition, the 2nd peak knee adduction (p = 0.01) and internal rotation (p = 0.001) moments were smaller in the no flares as compared to controls. The pain flare participants differed from controls with smaller knee internal rotation moments (p = 0.03), but greater relative hamstrings (vs. quadriceps) and medial (vs. lateral) muscle activation (p = 0.04, p = 0.04) compared to both controls and no flare participants (p = 0.04, p = 0.007). Following the 20MTW there were greater decreases in the 1st and 2nd peak knee adduction (p = 0.03; p = 0.02), and internal rotation (p = 0.002) moments for the pain flare as compared to the no flare group. In addition, for the pain flare as compared to controls, greater decreases in the knee flexion (p = 0.03) and internal rotation (p = 0.005) moments were found. Conclusions Individuals who adapt their gait to reduce knee joint loads may be less susceptible to exercise-induced pain flares. This highlights a potential role of gait biomechanics in short-term osteoarthritis pain fluctuations. The results also suggest that despite the chronic nature of osteoarthritis pain, the motor system’s ability to respond to nociceptive stimuli remains intact

The Nature of Age-Related Differences in Knee Function during Walking: Implication for the Development of Knee Osteoarthritis

Background Changes in knee kinematics have been identified in the early stages of osteoarthritis (OA). However, there is a paucity of information on the nature of kinematic change that occur with aging prior to the development of OA, This study applied a robust statistical method (Principal Component Analysis) to test the hypothesis that coupling between primary (flexion) and secondary (anterior-posterior translation, internal-external rotation) joint motions in walking would differ for age groupings of healthy subjects. Methods Seventy-four healthy participants divided into three groups with mean ages of 24 ± 2.3 years (younger), 48 ± 4.7years (middle-age) and 64 ± 2.4 years (older) were examined. Principal Component Analysis was used to characterize and statistically compare the patterns of knee joint movement and their relationships in walking. Results There were significant differences between the younger group and both the middle-age and older groups in the knee frontal plane angle and the coupling between knee flexion (PC1, p≤0.04) and the relative magnitudes of secondary plane motions in early and late stance (PC3, p\u3c0.01). Two additional principal components (PC2, p = 0.03 and PC5, p\u3c0.01) described differences in early stance knee flexion and relationship with secondary plane motion through-out stance for the older compared with middle-age group. Conclusions It appears there are changes in knee kinematics that occur with aging. The kinematic differences were identified for middle-aged as well as older adults suggesting midlife changes in neuromuscular physiology or behavior may have important consequences. These kinematic measures offer the potential to identify early markers for the risk of developing knee OA with aging

A paradigm shift is necessary to relate running injury risk and footwear design – comment on Nigg et al.

In this commentary, we respond to suggestions that new paradigms are needed to relate running-related injury risk and footwear design. We concur with the authors of this paper that the previous paradigms on which footwear were designed are faulty. We also concur with the authors that new paradigms are indeed needed and that research must take into consideration more epidemiological studies and more prospective biomechanical studies. The authors suggest new paradigms including muscle tuning, the preferred movement path and functional groups. However, we do raise questions about each of these suggestions regarding how these paradigms can be developed in future research designs

Which is the primary factor influencing running stride parameters: age or lower limb strength?

Much still remains unknown about the impact of age, and age-related changes in muscle function, on gait parameters. The aim of this study was to examine the impact of strength on running gait parameters across the adult lifespan. We tested the hypothesis that a greater amount of the variance in peak hip, knee and ankle sagittal plane moments would be explained by peak isometric joint torques as compared to age. Twenty-four healthy adults, ages 20-66 years, completed 5 trials on an overground 20-meter runway at a standardized velocity of 3.5 ms-1 (± 5%). Participants performed maximal isometric plantar flexion and knee extension for three contractions lasting three seconds each. Linear regression analysis between strength, age, and moments were performed. At the ankle, age alone explained 14.4% of the variance in the peak ankle joint moment. There was not a significant increase in the variance explained when strength was added to the model. At the knee, neither age nor strength explained a significant portion of the variance in peak knee moments. However, together age and strength explained 27.9% of the variance in the peak knee moment. No significant associations were found between the hip moments and either knee and ankle strength. These results suggest that other age-related physiological changes may drive changes in gait mechanics more so than maximal torque production. A more dynamic measure of muscle function, such as power or isokinetic torque at varying speeds may have greater predictive value for gait performance

THE INFLUENCE OF PATELLOFEMORAL PAIN ON COORDINATION VARIABILITY OVER A PROLONGED TREADMILL RUN

The purpose of this study was to understand the influence of patellofemoral pain on lower extremity segment coordination variability throughout a 21-minute treadmill run. Couplings between the pelvis, thigh, and shank were compared at the beginning and end of the run between healthy and injured runners. Average coordination variability in weight acceptance and mid-stance was increased in healthy runners over the course of the run and decreased in those experiencing pain. These results support the hypothesis that injured runners experiencing pain may not be as flexible to internal and external perturbations compared to their healthy counterparts. Thus, in the presence of pain, these runners may place greater stress on specific lower extremity tissues leading to greater risk for injury at these sites

MUSCLE ACTIVATION STRATEGIES DURING AN UNANTICIPATED STOPPING TASK

The purpose of this study was to determine how time constraints during stopping in sports affect lower limb muscle activation strategies in both the termination and stability steps. Rapid deceleration is common in both recreational and professional sport and has previously been associated with lower limb injury. To investigate control differences between anticipated and unanticipated stopping, total muscle activation and directed cocontraction ratios were used to analyse lower limb muscle activation. Increased plantar flexor and knee flexor activity was found during the pre-contact and weight acceptance phases of unanticipated stopping compared with anticipated stopping. These results support the hypothesis that lower limb muscle activity is altered when the task is unanticipated, which may place athletes at higher risk of lower limb injury in sport

A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas

Background Relapsed and refractory sarcomas continue to have poor survival rates. The cancer stem cell (CSC) theory provides a tractable explanation for the observation that recurrences occur despite dramatic responses to upfront chemotherapy. Preclinical studies demonstrated that inhibition of the mechanistic target of rapamycin (mTOR) sensitizes the CSC population to chemotherapy. Methods Here we present the results of the Phase II portion of a Phase I/II clinical trial that aimed to overcome the chemoresistance of sarcoma CSC by combining the mTOR inhibitor temsirolimus (20 mg/m2 weekly) with the chemotherapeutic agent liposomal doxorubicin (30 mg/m2 monthly). Results Fifteen patients with relapsed/refractory sarcoma were evaluable at this recommended Phase 2 dose level. The median progression free survival was 315 days (range 27–799). Response rate, defined as stable disease or better for 60 days, was 53%. Nine of the patients had been previously treated with doxorubicin. Therapy was well tolerated. In a small number of patients, pre- and post- treatment tumor biopsies were available for assessment of ALDH expression as a marker of CSCs and showed a correlation between response and decreased ALDH expression. We also found a correlation between biopsy-proven inhibition of mTOR and response. Conclusions Our study adds to the literature supporting the addition of mTOR inhibition to chemotherapy agents for the treatment of sarcomas, and proposes that a mechanism by which mTOR inhibition enhances the efficacy of chemotherapy may be through sensitizing the chemoresistant CSC population. Further study, ideally with pre- and post-therapy assessment of ALDH expression in tumor cells, is warranted. Trial registration The trial was registered on clinicaltrials.gov (NCT00949325) on 30 July 2009. http://www.editorialmanager.com/csrj/default.asp