Brain compensatory mechanisms in depression and memory complaints in fibromyalgia: The role of theta oscillatory activity.

BACKGROUND: The different clinical presentations of fibromyalgia (FMS) may play independent roles in the unclear etiology of cognitive impairments and depressive symptoms seen in this population. Understanding how these clinical presentations are associated with FMS's clinical and neurophysiological aspects is important when developing effective treatments. AIM: To explore the relationship between memory complaints and depressive symptoms, and the different clinical and neurophysiological characteristics of FMS. METHODS: Cross-sectional data analysis from a randomized clinical trial. Baseline demographics, physical fitness, sleep, anxiety, depression, cortical excitability, and pain (clinical and mechanistic) data from 63 FMS subjects were used. Multiple linear and logistic association models were constructed. RESULTS: Final regression models including different sets of predictions were statistically significant (p < 0.001), explaining approximately 50% of the variability in cognitive complaints and depression status. Older subjects had higher levels of anxiety, poor sleep quality, lower motor threshold, and higher relative theta power in the central area, are more likely to have clinical depression. Higher anxiety, pain and theta power were associated with an increase memory complaint. CONCLUSION: Depression symptoms seem to be associated with TMS-indexed motor threshold and psychosocial variables, while memory complaints are associated with pain intensity and higher theta oscillations. These mechanisms may be catalyzed and/or triggered by some behavioral and clinical features such as older age, sleep disruption, and anxiety. The correlation with clinical variables suggests the increasing of theta oscillations is a compensatory response in patients with FMS, which can be explored in future studies to improve the treatment for FMS.

The Analgesic Effect of Transcranial Direct Current Stimulation in Fibromyalgia: A Systematic Review, Meta-Analysis, and Meta-Regression of Potential Influencers of Clinical Effect.

BACKGROUND: There is tentative evidence to support the analgesic effect of transcranial direct current stimulation (tDCS) in fibromyalgia (FM), with large variability in the effect size (ES) encountered in different clinical trials. Understanding the source of the variability and exploring how it relates to the clinical results could characterize effective neuromodulation protocols and ultimately guide care in FM pain. The primary objective of this study was to determine the effect of tDCS in FM pain as compared with sham tDCS. The secondary objective was to explore the relationship of methodology, population, and intervention factors and the analgesic effect of tDCS in FM. MATERIALS AND METHODS: For the primary objective, a systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized clinical trials (RCTs) investigating tDCS as an intervention for FM pain were searched in MEDLINE, Embase, and the Web Of Science. Studies were excluded if they used cross-over designs or if they did not use tDCS as an intervention for pain or did not measure clinical pain. Analysis for the main outcome was performed using a random-effects model. Risk of bias and evidence certainty were assessed for all studies using Cochrane Risk of Bias and Grading of Recommendations Assessment, Development, and Evaluation tools. For the secondary objective, a meta-regression was conducted to explore methodology, population, and intervention factors potentially related to the ES. RESULTS: Sixteen RCTs were included. Six studies presented a high risk of bias. Significant reduction in pain scores were found for FM (standardized mean difference = 1.22, 95% CI = 0.80-1.65, p < 0.001). Subgroup analysis considering tDCS as a neural target revealed no differences between common neural sites. Meta-regression revealed that the duration of the tDCS protocol in weeks was the only factor associated with the ES, in which protocols that lasted four weeks or longer reported larger ES than shorter protocols. CONCLUSIONS: Results suggest an analgesic effect of tDCS in FM. tDCS protocols that last four weeks or more may be associated with larger ESs. Definite conclusions are inadequate given the large heterogeneity and limited quality of evidence of the included studies.

Insights and Future Directions on the Combined Effects of Mind-Body Therapies with Transcranial Direct Current Stimulation: An Evidence-based Review.

Mind-body therapies (MBTs) use mental abilities to modify electrical neural activity across brain networks. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates neuronal membrane potentials to enhance neuroplasticity. A combination of these treatment strategies may generate synergistic or additive effects, and thus has been more commonly tested in clinical trials, fostering a novel yet promising field of research. We conducted a literature search in four different databases including only randomized clinical trials (RCTs) that tested the combination of MBTs with tDCS. Ten studies (n=461) were included. Combined protocols included meditation/mindfulness (8/10), biofeedback (1/10), and hypnosis (1/10). The RCTs were heterogeneous with regards to population, design, and types of outcomes. Based on the findings of this search, we provide here a content description, methodological and practical insights, and future directions for the field. We hope this review will provide future authors with information to facilitate the development of trials with improved protocols.

Temporal Summation in Fibromyalgia Patients: Comparing Phasic and Tonic Paradigms.

Introduction: Fibromyalgia (FM) is associated with dysfunctional pain modulation mechanisms, including central sensitization. Experimental pain measurements, such as temporal summation (TS), could serve as markers of central sensitization and have been previously studied in these patients, with conflicting results. Our objective in this study was to explore the relationships between two different protocols of TS (phasic and tonic) and test the associations between these measures and other clinical variables. Materials and Methods: In this cross-sectional analysis of a randomized clinical trial, patients were instructed to determine their pain-60 test temperature, then received one train of 15 repetitive heat stimuli and rated their pain after the 1st and 15th stimuli: TSPS-phasic was calculated as the difference between those. We also administered a tonic heat test stimulus at the same temperature continuously for 30 s and asked them to rate their pain levels after 10 s and 30 s, calculating TSPS-tonic as the difference between them. We also collected baseline demographic data and behavioral questionnaires assessing pain, depression, fatigue, anxiety, sleepiness, and quality of life. We performed univariable analyses of the relationship between TSPS-phasic and TSPS-tonic, and between each of those measures and the demographic and clinical variables collected at baseline. We then built multivariable linear regression models to find predictors for TSPS-phasic and TSPS-tonic, while including potential confounders and avoiding collinearity. Results: Fifty-two FM patients were analyzed. 28.85% developed summation during the TSPS-phasic protocol while 21.15% developed summation during the TSPS-tonic protocol. There were no variables associated TSPS phasic or tonic in the univariable analyses and both measures were not correlated. On the multivariate model for the TSPS-phasic protocol, we found a weak association with pain variables. BPI-pain subscale was associated with more temporal summation in the phasic protocol (ß = 0.38, p = 0.029), while VAS for pain was associated with less summation in the TSPS-tonic protocol (ß = -0.5, p = 0.009). Conclusion: Our results suggest that, using heat stimuli with pain-60 temperatures, a TSPS-phasic protocol and a TSPS-tonic protocol are not correlated and could index different neural responses in FM subjects. Further studies with larger sample sizes would be needed to elucidate whether such responses could help differentiating subjects with FM into specific phenotypes.

EEG theta and beta bands as brain oscillations for different knee osteoarthritis phenotypes according to disease severity.

This study aims to investigate the multivariate relationship between different sociodemographic, clinical, and neurophysiological variables with resting-state, high-definition, EEG spectral power in subjects with chronic knee osteoarthritis (OA) pain. This was a cross-sectional study. Sociodemographic and clinical data were collected from 66 knee OA subjects. To identify associated factors, we performed independent univariate and multivariate regression models by frequency bands (delta, theta, alpha, beta, low-beta, and high-beta) and by pre-defined regions (frontal, central, and parietal). From adjusted multivariate models, we found that: (1) increased frontocentral high-beta power and reduced central theta activity are positively correlated with pain intensity (ß = 0.012, 95% CI 0.004-0.020; and ß = - 0.008; 95% CI 0.014 to - 0.003; respectively); (2) delta and alpha oscillations have a direct relationship with higher cortical inhibition; (3) diffuse increased power at low frequencies (delta and theta) are associated with poor cognition, aging, and depressive symptoms; and (4) higher alpha and beta power over sensorimotor areas seem to be a maladaptive compensatory mechanism to poor motor function and severe joint degeneration. Subjects with higher pain intensity and higher OA severity (likely subjects with maladaptive compensatory mechanisms to severe OA) have higher frontocentral beta power and lower theta activity. On the other hand, subjects with less OA severity and less pain have higher theta oscillations power. These associations showed the potential role of brain oscillations as a marker of pain intensity and clinical phenotypes in chronic knee OA patients. Besides, they suggest a potential compensatory mechanism of these two brain oscillators according to OA severity.

Electroencephalography Signatures for Conditioned Pain Modulation and Pain Perception in Nonspecific Chronic Low Back Pain-An Exploratory Study.

Conditioned pain modulation (CPM) can discriminate between healthy and chronic pain patients. However, its relationship with neurophysiological pain mechanisms is poorly understood. Brain oscillations measured by electroencephalography (EEG) might help gain insight into this complex relationship. OBJECTIVE: To investigate the relationship between CPM response and self-reported pain intensity in non-specific chronic low back pain (NSCLBP) and explore respective EEG signatures associated to these mechanisms. DESIGN: Cross-sectional analysis. PARTICIPANTS: Thirty NSCLBP patients participated. METHODS: Self-reported low back pain, questionnaires, mood scales, CPM (static and dynamic quantitative sensory tests), and resting surface EEG data were collected and analyzed. Linear regression models were used for statistical analysis. RESULTS: CPM was not significantly correlated with self-reported pain intensity scores. Relative power of EEG in the beta and high beta bands as recorded from the frontal, central, and parietal cortical areas were significantly associated with CPM. EEG relative power at delta and theta bands as recorded from the central area were significantly correlated with self-reported pain intensity scores while controlling for self-reported depression. CONCLUSIONS: Faster EEG frequencies recorded from pain perception areas may provide a signature of a potential cortical compensation caused by chronic pain states. Slower EEG frequencies may have a critical role in abnormal pain processing.

Development of a Clinical Prediction Rule for Treatment Success with Transcranial Direct Current Stimulation for Knee Osteoarthritis Pain: A Secondary Analysis of a Double-Blind Randomized Controlled Trial.

The study's objective was to develop a clinical prediction rule that predicts a clinically significant analgesic effect on chronic knee osteoarthritis pain after transcranial direct current stimulation treatment. This is a secondary analysis from a double-blind randomized controlled trial. Data from 51 individuals with chronic knee osteoarthritis pain and an impaired descending pain inhibitory system were used. The intervention comprised a 15-session protocol of anodal primary motor cortex transcranial direct current stimulation. Treatment success was defined by the Western Ontario and McMaster Universities' Osteoarthritis Index pain subscale. Accuracy statistics were calculated for each potential predictor and for the final model. The final logistic regression model was statistically significant (p < 0.01) and comprised five physical and psychosocial predictor variables that together yielded a positive likelihood ratio of 14.40 (95% CI: 3.66−56.69) and an 85% (95%CI: 60−96%) post-test probability of success. This is the first clinical prediction rule proposed for transcranial direct current stimulation in patients with chronic pain. The model underscores the importance of both physical and psychosocial factors as predictors of the analgesic response to transcranial direct current stimulation treatment. Validation of the proposed clinical prediction rule should be performed in other datasets.

Increased motor cortex inhibition as a marker of compensation to chronic pain in knee osteoarthritis.

This study aims to investigate the associative and multivariate relationship between different sociodemographic and clinical variables with cortical excitability as indexed by transcranial magnetic stimulation (TMS) markers in subjects with chronic pain caused by knee osteoarthritis (OA). This was a cross-sectional study. Sociodemographic and clinical data were extracted from 107 knee OA subjects. To identify associated factors, we performed independent univariate and multivariate regression models per TMS markers: motor threshold (MT), motor evoked potential (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). In our multivariate models, the two markers of intracortical inhibition, SICI and CSP, had a similar signature. SICI was associated with age (ß: 0.01), WOMAC pain (ß: 0.023), OA severity (as indexed by Kellgren-Lawrence Classification) (ß: - 0.07), and anxiety (ß: - 0.015). Similarly, CSP was associated with age (ß: - 0.929), OA severity (ß: 6.755), and cognition (as indexed by the Montreal Cognitive Assessment) (ß: - 2.106). ICF and MT showed distinct signatures from SICI and CSP. ICF was associated with pain measured through the Visual Analogue Scale (ß: - 0.094) and WOMAC (ß: 0.062), and anxiety (ß: - 0.039). Likewise, MT was associated with WOMAC (ß: 1.029) and VAS (ß: - 2.003) pain scales, anxiety (ß: - 0.813), and age (ß: - 0.306). These associations showed the fundamental role of intracortical inhibition as a marker of adaptation to chronic pain. Subjects with higher intracortical inhibition (likely subjects with more compensation) are younger, have greater cartilage degeneration (as seen by radiographic severity), and have less pain in WOMAC scale. While it does seem that ICF and MT may indicate a more acute marker of adaptation, such as that higher ICF and MT in the motor cortex is associated with lesser pain and anxiety.

Recruitment characteristics and non-adherence associated factors of fibromyalgia patients in a randomized clinical trial: A retrospective survival analysis.

INTRODUCTION: Fibromyalgia is a complex pain condition that affects mostly women. Given the disease's lack of understanding, patients report poor adherence to medication and mistrust of medical services. This study aims to describe the recruitment characteristics and non-adherence associated factors of fibromyalgia patients to an RCT. METHODS: We performed a retrospective longitudinal analysis with data from our ongoing RCT. We investigated characteristics of subjects recruited, consented, and randomized. Adherence was studied using survival analysis techniques, and its associated factors were identified using Cox proportional hazards regression model. RESULTS: 524 subjects were contacted, 269 were eligible, 61 consented and 40 subjects were randomized. Thirty-eight percent were non-adherent to the protocol with a median of visits of five. The recruitment survey reported that 90% would likely participate in RCTs, 52% had previous participation, and 19% were aware of RCTs by their physicians. Some barriers were investigator-related (staff's friendliness and receiving the results of their trial participation) and center-related (privacy-confidentiality issues and the institution's reputation), without difference between adherent and non-adherent participants. We report significant factors for non-adherence as VAS anxiety score of 5 or more (5.3 HR, p = 0.01), Body Mass Index (BMI) (0.91 HR, p = 0.041) and Quality of Life (QoL) - Personal development subdomain (0.89 HR, p = 0.046). CONCLUSION: Recruitment and adherence of fibromyalgia patients is a challenge; however, they seem eager to participate in RCTs. We recommend creating a comfortable, friendly and trusting environment to increase the recruitment rate. Higher anxiety, lower BMI and lower quality of life were associated with a higher attrition rate.

Understanding intracortical excitability in phantom limb pain: A multivariate analysis from a multicenter randomized clinical trial.

OBJECTIVES: To explore associations of intracortical excitability with clinical characteristics in a large sample of subjects with phantom limb pain (PLP). METHODS: Ancillary study using baseline and longitudinal data from a large multicenter randomized trial that investigated the effects of non-invasive brain stimulation combined with sensorimotor training on PLP. Multivariate regression modeling analyses were used to investigate the association of intracortical excitability, measured by percentages of intracortical inhibition (ICI) and facilitation (ICF) with clinical variables. RESULTS: Ninety-eight subjects were included. Phantom sensation of itching was positively associated with ICI changes and at baseline in the affected hemisphere (contralateral to PLP). However, in the non-affected hemisphere (ipsilateral to PLP), the phantom sensation of warmth and PLP intensity were negatively associated with ICI (both models). For the ICF, PLP intensity (baseline model only) and age (longitudinal model) were negatively associated, while time since amputation and amputation level (both for longitudinal model only) were positively associated in the affected hemisphere. Additionally, use of antidepressants led to lower ICF in the non-affected hemisphere for the baseline model while higher amputation level also led to less changes in the ICF. CONCLUSION: Results revealed clear associations of clinical variables and cortical excitability in a large chronic pain sample. ICI and ICF changes appear not to be mainly explained by PLP intensity. Instead, other variables associated with duration of neuroplasticity changes (such as age and duration of amputation) and compensatory mechanisms (such as itching and phantom limb sensation) seem to be more important in explaining these variables.

Home-based transcranial direct current stimulation (tDCS) and motor imagery for phantom limb pain using statistical learning to predict treatment response: an open-label study protocol.

Background: Phantom limb pain (PLP) management has been a challenge due to its response heterogeneity and lack of treatment access. This study will evaluate the feasibility of a remotely home-based M1 anodal tDCS combined with motor imagery in phantom limb patients and assess the preliminary efficacy, safety, and predictors of response of this therapy. Methods: This is a pilot, single-arm, open-label trial in which we will recruit 10 subjects with phantom limb pain. The study will include 20 sessions. All participants will receive active anodal M1 tDCS combined with phantom limb motor imagery training. Our primary outcome will be the acceptability and feasibility of this combined intervention. Moreover, we will assess preliminary clinical (pain intensity) and physiological (motor inhibition tasks and heart rate variability) changes after treatment. Finally, we will implement a supervised statistical learning (SL) model to identify predictors of treatment response (to tDCS and phantom limb motor imagery) in PLP patients. We will also use data from our previous clinical trial (total observations=224 [n=112 x timepoints = 2)) for our statistical learning algorithms. The new prospective data from this open-label study will be used as an independent test dataset. Discussion: This protocol proposes to assess the feasibility of a novel, neuromodulatory combined intervention that will allow the design of larger remote clinical trials, thus increasing access to safe and effective treatments for PLP patients. Moreover, this study will allow us to identify possible predictors of pain response and PLP clinical endotypes.

The Analgesic Effect of Transcranial Direct Current Stimulation (tDCS) combined with Physical Therapy on Common Musculoskeletal Conditions: A Systematic Review and Meta-Analysis.

BACKGROUND: The analgesic effects of transcranial Direct Current Stimulation (tDCS) combined with physical therapy remain unclear. OBJECTIVE: To systematically review available evidence comparing tDCS with any physical therapy modality (PTM) to PTM alone or PTM with sham tDCS on pain relief on common musculoskeletal (MSK) conditions, namely knee osteoarthritis (KOA), chronic low back pain (CLBP), myofascial pain syndrome (MPS) and fibromyalgia. METHODS: EMBASE and MEDLINE were searched from inception to April 2019 for randomized controlled trials. Reviewers independently assessed the studies quality and extracted data according to the PRISMA protocol. The GRADE approach was used to asses quality of evidence and a "Summary of Findings" table was created. The analyses used random-effects model. The primary outcome was pain reduction after treatment. RESULTS: Eight articles were included. Only one study had low risk of bias. Quality of evidence was considered low or very low. Significant reduction in pain scores were found for fibromyalgia and KOA (Standardized mean difference (SMD) = -1.94 [95% CI: -3.37 to -0.49; I 2=76.4%] and SMD = -2.35 [95% CI: -3.63 to -1.06; I 2=69.7%] respectively). Subgroup analysis considering the type of PTM despite MSK condition revealed significant reduction in pain scores for exercise, SMD = -1.20 [95% CI: -1.683 to -0.717; I 2=10.8%]. CONCLUSIONS: Large heterogeneity and low quality of evidence and limited number of studies were found. Results suggest a potential analgesic effect of tDCS in combination with a PTM for fibromyalgia and KOA. Subgroup analysis suggests a stronger effect of tDCS when combined with an exercise based PTM.

Pain perception in chronic knee osteoarthritis with varying levels of pain inhibitory control: an exploratory study.

Background and aims Pain is a disabling symptom in knee osteoarthritis (KOA) and its underlying mechanism remains poorly understood. Dysfunction of descending pain modulatory pathways and reduced pain inhibition enhance pain facilitation in many chronic pain syndromes but do not fully explain pain levels in chronic musculoskeletal conditions. The objective of this study is to explore the association of clinical variables with pain intensity perception in KOA individuals with varying levels of Conditioned Pain Modulation (CPM) response. Methods This is a cross-sectional, exploratory analysis using baseline data of a randomized clinical trial investigating the effects of a non-invasive brain stimulation treatment on the perception of pain and functional limitations due to KOA. Sixty-three subjects with KOA were included in this study. Data on pain perception, mood perception, self-reported depression, physical function, quality of life, and quantitative sensory testing was collected. Multiple linear regression analysis was performed to explore the association between the clinical variables with pain perception for individuals with different levels of CPM response. Results For KOA patients with limited CPM response, perception of limitations at work/other activities due to emotional problems and stress scores were statistically significantly associated with pain scores, F(2, 37) = 7.02, p < 0.01. R-squared = 0.275. For KOA patients with normal CPM response, general health perception scores were statistically significantly associated with pain scores, F(1, 21) = 5.60, p < 0.05. R-squared = 0.2104. Limitations of this study include methodology details, small sample size and study design characteristics. Conclusions Pain intensity perception is associated differently with clinical variables according to the individual CPM response. Mechanistic models to explain pain perception in these two subgroups of KOA subjects are discussed.

Top 100 cited noninvasive neuromodulation clinical trials.

INTRODUCTION: Introduction: Transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are noninvasive neuromodulation techniques used as therapeutic and research tools for several neuropsychiatric conditions. Given the exponential scientific growth of this field, we aimed to systematically review the most cited clinical trials using TMS or tDCS. AREAS COVERED: A de-novo keyword search strategy identified and characterized the 100 most-cited trials. Total citation count for the most cited trials was 13,204. Articles were published between 2008 and 2014 in 50 different journals with a median impact factor of 6.52 (IQR 3.37). Almost half of the top cited papers were investigating mechanisms of action in healthy subjects. Most studies were feasibility trials and only five were pivotal trials, including the ones used for recent FDA approval. Seven articles were interlinked with another article by at least 25 citations and eight authors had collaborated with at least one other author. EXPERT OPINION: Although there has been a significant increase in interest for rTMS and tDCS, most of the cited clinical trials are still small feasibility studies, what reinforced the need for more robust clinical trials (larger samples sizes and effects sizes) to better define clinical effectiveness.

Effects of impairment-based exercise on performance of specific self-reported functional tasks in individuals with knee osteoarthritis.

BACKGROUND: Little is known regarding how impairment-based exercises may improve performance of specific functional tasks in people with knee osteoarthritis (OA). OBJECTIVE: The purpose of this study was to compare the probability that participation in an impairment-based exercise program or the same impairment-based program supplemented with agility and perturbation training will improve patient-reported function on specific functional tasks. DESIGN: This study was a secondary analysis of data from a randomized clinical trial. SETTING: The study was conducted in the outpatient physical therapy clinic of a large, university-based health center. PARTICIPANTS: One hundred eighty-three people with knee OA (122 women, 61 men) participated. INTERVENTIONS: Participants were randomly assigned to either a group that received agility and perturbation training with standard exercise therapy or a group that received only the standard exercise. MEASUREMENTS: Specific functional items were taken from the physical function subscale of the Western Ontario and McMasters Universities Osteoarthritis Index, the Lower Extremity Function Scale, and the Activities of Daily Living Scale of the Knee Outcome Survey. RESULTS: The probability of self-reported improvement in a variety of specific functional tasks was low following participation in either of the exercise programs. When only participants with moderate to severe difficulty performing specific functional tasks were considered in the analysis, the probability of success improved but was still limited. LIMITATIONS: The results are generalizable only to self-reported assessment of performance of specific functional tasks. CONCLUSIONS: Impairment-based exercise may not be enough to make substantial improvement in performance of specific functional tasks. Task-specific exercise approaches need to be explored for people with knee OA.

Contribution of hip abductor strength to physical function in patients with total knee arthroplasty.

BACKGROUND: Investigating modifiable factors that contribute to functional limitations in patients with total knee arthroplasty (TKA) may guide changes in rehabilitation protocols and improve functional outcomes. Whereas quadriceps muscle weakness has been demonstrated to contribute to functional limitations in TKA, the role of hip abductor weakness has not received attention. OBJECTIVE: The purpose of this study was to determine whether hip abductor strength (force-generating capacity) contributes to physical function beyond what can be explained by quadriceps muscle strength in patients after a TKA. DESIGN: A cross-sectional design was used in the study. SETTING: The study was conducted in a clinical laboratory at an academic center. PATIENTS: Thirty-one people with TKA (74% female; mean age=68 years, SD=8; mean body mass index=31 kg/m(2), SD=5) participated in the study. MEASUREMENTS: Strength of quadriceps muscles and hip abductors was measured using an isokinetic dynamometer. Performance-based physical function was assessed with 4 measures: self-selected walking speed, the Figure-of-8 Walk Test, the Stair Ascend/Descend Test, and the 5-Chair Rise Test. Self-reported physical function was assessed with the Western Ontario and McMaster Universities Osteoarthritis Index Physical Function Subscale. RESULTS: In hierarchical regression models, after accounting for demographic and anthropometric factors, quadriceps muscle strength was associated with performance on the Stair Ascend/Descend Test. After accounting for demographic, anthropometric, and quadriceps strength, hip abductor strength was associated with performance on the Stair Ascend/Descend Test, the Figure-of-8 Walk Test, and the 5-Chair Rise Test. LIMITATIONS: The study design precluded ascertainment of causal relationships. CONCLUSIONS: After TKA, hip abductor strength influenced physical function in participants more than did demographic or anthropometric measures or quadriceps strength. Longitudinal studies with larger samples are warranted. If findings are replicated, they will justify targeting the hip abductors during rehabilitation after TKA.