Pain, comorbidities, and clinical decision-making: conceptualization, development, and pilot testing of the Pain in Aging, Educational Assessment of Need instrument.

Introduction: Pain is highly prevalent in older adults and often contextualized by multiple clinical conditions (pain comorbidities). Pain comorbidities increase with age and this makes clinical decisions more complex. To address gaps in clinical training and geriatric pain management, we established the Pain in Aging-Educational Assessment of Need (PAEAN) project to appraise the impacts of medical and mental health conditions on clinical decision-making regarding older adults with pain. We here report development and pilot testing of the PAEAN survey instrument to assess clinician perspectives. Methods: Mixed-methods approaches were used. Scoping review methodology was applied to appraise both research literature and selected Medicare-based data. A geographically and professionally diverse interprofessional advisory panel of experts in pain research, medical education, and geriatrics was formed to advise development of the list of pain comorbidities potentially impacting healthcare professional clinical decision-making. A survey instrument was developed, and pilot tested by diverse licensed healthcare practitioners from 2 institutions. Respondents were asked to rate agreement regarding clinical decision-making impact using a 5-point Likert scale. Items were scored for percent agreement. Results: Scoping reviews indicated that pain conditions and comorbidities are prevalent in older adults but not universally recognized. We found no research literature directly guiding pain educators in designing pain education modules that mirror older adult clinical complexity. The interprofessional advisory panel identified 26 common clinical conditions for inclusion in the pilot PAEAN instrument. Conditions fell into three main categories: "major medical", i.e., cardio-vascular-pulmonary; metabolic; and neuropsychiatric/age-related. The instrument was pilot tested by surveying clinically active healthcare providers, e.g., physicians, nurse practitioners, who all responded completely. Median survey completion time was less than 3 min. Conclusion: This study, developing and pilot testing our "Pain in Aging-Educational Assessment of Need" (PAEAN) instrument, suggests that 1) many clinical conditions impact pain clinical decision-making, and 2) surveying healthcare practitioners about the impact of pain comorbidities on clinical decision-making for older adults is highly feasible. Given the challenges intrinsic to safe and effective clinical care of older adults with pain, and attendant risks, together with the paucity of existing relevant work, much more education and research are needed.

Exploring different models of pain phenotypes and their association with pain worsening in people with early knee osteoarthritis: The MOST cohort study.

OBJECTIVE: To determine i) pain phenotypes (PP) in people with early-stage knee osteoarthritis (EKOA); ii) the longitudinal association between the phenotypes and pain worsening at two years. DESIGN: We studied participants with EKOA from the Multicenter Osteoarthritis Study defined as pain intensity ≤3/10, Kellgren and Lawrence grade ≤2, intermittent pain none to sometimes, and no constant pain. Two models of PP were explored. Model A included pressure pain thresholds, temporal summation, conditioned pain modulation, pain catastrophizing, sleep quality, depression, and widespread pain (WSP). In Model B, gait characteristics, quadriceps strength, comorbidities, and magnetic resonance imaging features were added to Model A. Latent Class Analysis was used to create phenotypes, and logistic regression was used to determine their association with pain worsening. RESULTS: 750 individuals (60% females), mean age [standard deviation (SD)]: 60.3 (9.4) were included in Model A and 333 individuals (60% females), mean age (SD): 59.4 (8.1) in Model B. 3-class and 4-class solutions were chosen for Model A and Model B. In Model A, the most "severe" phenotype was dominated by psychosocial factors, WSP, and measures of nervous system sensitization. Similarly in Model B, the Model A phenotype plus gait variables, quadriceps strength, and comorbidities were dominant. Surprisingly, none of the phenotypes in either model had a significant relationship with pain worsening. CONCLUSION: Phenotypes based upon various factors thought to be important for the pain experience were identified in those with EKOA but were not significantly related to pain worsening. These phenotypes require validation with clinically relevant endpoints.

Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures.

ABSTRACT: Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

Applying a muscle fatigue model when optimizing load-sharing between muscles for short-duration high-intensity exercise: A preliminary study.

Introduction: Multiple different mathematical models have been developed to represent muscle force, to represent multiple muscles in the musculoskeletal system, and to represent muscle fatigue. However, incorporating these different models together to describe the behavior of a high-intensity exercise has not been well described. Methods: In this work, we adapted the three-compartment controller (3CCr) muscle fatigue model to be implemented with an inverse-dynamics based optimization algorithm for the muscle recruitment problem for 7 elbow muscles to model a benchmark case: elbow flexion/extension moments. We highlight the difficulties in achieving an accurate subject-specific approach for this multi-level modeling problem, considering different muscular models, compared with experimental measurements. Both an isometric effort and a dynamic bicep curl were considered, where muscle activity and resting periods were simulated to obtain the fatigue behavior. Muscle parameter correction, scaling and calibration are addressed in this study. Moreover, fiber-type recruitment hierarchy in force generation was added to the optimization problem, thus offering an additional novel muscle modeling criterion. Results: It was observed that: i) the results were most accurate for the static case; ii) insufficient torque was predicted by the model at some time points for the dynamic case, which benefitted from a more precise calibration of muscle parameters; iii) modeling the effects of muscular potentiation may be important; and iv) for this multilevel model approach, the 3CCr model had to be modified to avoid reaching situations of unrealistic constant fatigue in high intensity exercise-resting cycles. Discussion: All the methods yield reasonable estimations, but the complexity of obtaining accurate subject-specific human models is highlighted in this study. The proposed novel muscle modeling and force recruitment criterion, which consider the muscular fiber-type distinction, show interesting preliminary results.

Multisensory sensitivity differentiates between multiple chronic pain conditions and pain-free individuals.

ABSTRACT: Multisensory sensitivity (MSS) to nonpainful stimuli has been identified as a risk factor for the presence of coexisting chronic pain conditions. However, it remains unclear whether MSS can differentiate pain phenotypes involving different levels of central sensitivity. Both pain-free and those with chronic pain, particularly fibromyalgia (FM), migraine, or low back pain (LBP) were recruited, with pain comorbidities assessed. MSS was highest in FM, followed by migraine, then LBP, and lowest in pain-free individuals (adjusted between condition Cohen d = 0.32-1.2, P ≤ 0.0007). However, when secondly grouping patients by the total number of pain comorbidities reported, those with a single pain condition (but not FM) did not have significantly elevated MSS vs pain-free individuals (adj d= 0.17, P = 0.18). Elevated MSS scores produced increased odds of having 2 or more pain comorbidities; OR [95% CI] =2.0 [1.15, 3.42], without, and 5.6 [2.74, 11.28], with FM ( P ≤ 0.0001). Furthermore, those with low MSS levels were 55% to 87% less likely to have ≥ 2 pain comorbidities with or without FM (OR 0.45 [0.22, 0.88]-0.13 [0.05, 0.39]; P ≤ 0.0001). Our findings support that MSS can differentiate between pain phenotypes with different degrees of expected central mechanism involvement and also serve as a risk and resilience marker for total coexisting chronic pain conditions. This supports the use of MSS as a marker of heightened central nervous system processing and thus may serve as a clinically feasible assessment to better profile pain phenotypes with the goal of improving personalized treatment.

A comparison of pain, fatigue, and function between post-COVID-19 condition, fibromyalgia, and chronic fatigue syndrome: a survey study.

ABSTRACT: A growing number of individuals report prolonged symptoms following acute Coronavirus-19 (COVID-19) infection, known as post-COVID-19 condition (post-COVID-19). While studies have emerged investigating the symptom sequelae of post-COVID-19, there has been limited investigation into the characterization of pain, fatigue, and function in these individuals, despite initial reports of a clinical phenotype similar to fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME). This study aimed to characterize multiple symptom domains in individuals reporting post-COVID-19 and compare its clinical phenotype with those with FMS and CFS. A total of 707 individuals with a single or comorbid diagnosis of post-COVID-19, FMS, and/or CFS completed multiple surveys assessing self-reported pain, fatigue, physical and cognitive function, catastrophizing, kinesiophobia, anxiety, depression, dyspnea, and sleep quality. In all 3 diagnoses, elevated pain, fatigue, anxiety, depression, catastrophizing, and kinesiophobia were reported. Physical and cognitive function were similarly impacted among individuals with post-COVID-19, FMS, and CFS; however, individuals with post-COVID-19 reported lower pain and fatigue than FMS and CFS. The comorbid diagnosis of post-COVID-19 with FMS and/or CFS further exacerbated pain, fatigue, and psychological domains when compared with post-COVID-19 alone. In summary, individuals with post-COVID-19 report a symptom phenotype similar to FMS and CFS, negatively impacting cognitive and physical function, but with less severe pain and fatigue overall. These findings may help direct future investigations of the benefit of a biopsychosocial approach to the clinical management of post-COVID-19.

Resistance training protects against muscle pain through activation of androgen receptors in male and female mice.

ABSTRACT: Resistance training-based exercise is commonly prescribed in the clinic for the treatment of chronic pain. Mechanisms of aerobic exercise for analgesia are frequently studied, while little is known regarding resistance training mechanisms. We developed a resistance training model in mice and hypothesized resistance training would protect against development of muscle pain, mediated through the activation of androgen receptors. Activity-induced muscle hyperalgesia was produced by 2 injections of pH 5.0 stimuli with fatiguing muscle contractions. Resistance training was performed by having mice climb a ladder with attached weights, 3 times per week. Resistance training acutely increased blood lactate and prolonged training increased strength measured via forepaw grip strength and 1 repetition maximum, validating the exercise program as a resistance training model. Eight weeks of resistance training prior to induction of the pain model blocked the development of muscle hyperalgesia in both sexes. Resistance training initiated after induction of the pain model reversed muscle hyperalgesia in male mice only. A single resistance training bout acutely increased testosterone in male but not female mice. Administration of the androgen receptor antagonist flutamide (200 mg pellets) throughout the 8-week training program blocked the exercise-induced protection against muscle pain in both sexes. However, single administration of flutamide (1, 3, 10 mg/kg) in resistance-trained animals had no effect on existing exercise-induced protection against muscle pain. Therefore, resistance training acutely increases lactate and testosterone and strength overtime. Eight weeks of resistance training prevents the development of hyperalgesia through the activation of androgen receptors in an animal model of muscle pain.

Assessing Multisensory Sensitivity Across Scales: Using the Resulting Core Factors to Create the Multisensory Amplification Scale.

Multisensory sensitivity (MSS), observed in some chronic pain patients, may reflect a generalized central nervous system sensitivity. While several surveys measure aspects of MSS, there remains no gold standard. We explored the underlying constructs of 4 MSS-related surveys (80 items in total) using factor analyses using REDCap surveys (N = 614, 58.7% with pain). Four core- and 6 associated-MSS factors were identified from the items assessed. None of these surveys addressed all major sensory systems and most included additional related constructs. A revised version of the Somatosensory Amplification Scale was developed, encompassing 5 core MSS systems: vision, hearing, smell, tactile, and internal bodily sensations: the 12-item Multisensory Amplification Scale (MSAS). The MSAS demonstrated good internal consistency (alpha = 0.82), test-retest reliability (ICC3,1 = 0.90), and construct validity in the original and in a new, separate cohort (R = 0.54-0.79, P < .0001). Further, the odds of having pain were 2-3.5 times higher in the highest sex-specific MSAS quartile relative to the lowest MSAS quartile, after adjusting for age, sex, BMI, and pain schema (P < .03). The MSAS provides a psychometrically comprehensive, brief, and promising tool for measuring the core-dimensions of MSS. PERSPECTIVE: Multiple multisensory sensitivity (MSS) tools are used, but without exploration of their underlying domains. We found several measures lacking core MSS domains, thus we modified an existing scale to encompass 5 core MSS domains: light, smell, sound, tactile, and internal bodily sensations using only 12 items, with good psychometric properties.

Quantitative Sensory Changes Related to Physical Activity in Adult Populations: A Scoping Review.

ABSTRACT: Exercise-induced hypoalgesia related to physical activity produces sensory adaptations, but its mechanism remains unclear. Quantitative sensory testing is an effective measurement tool to identify sensory changes, but the extent of evidence linking quantitative sensory testing and physical activity has not been explored. The purpose of this scoping review is to synthesize the evidence on using quantitative sensory testing to evaluate psychophysical changes related to physical activity in adult populations. The researchers developed a comprehensive search strategy with a Health Sciences Librarian using the Arksey and O'Malley Methodological framework. Four databases (Medline [PubMed], CINAHL, Web of Science, and Embase) were searched for peer-reviewed primary research. After 2790 articles were evaluated, 196 studies were included for final review. More than half of studies used randomized controlled trial design (50.5%), followed by quasi-experimental (24.0%) and observational (25.5%) strategies. Healthy adults (42.9%) and individuals with chronic health conditions (20.9%) were examined most frequently. Aerobic (27.6%) and strength (21.4%) physical activity types were most commonly studied. Static quantitative sensory testing measures of pressure pain threshold (84%) were used most frequently. The findings of this scoping review demonstrate available evidence for quantitative sensory testing as a measurement tool of neuromodulation related to physical activity in adult populations. A systematic review is warranted to examine outcomes and recommendations.

Multisensory Sensitivity is Related to Deep-Tissue but Not Cutaneous Pain Sensitivity in Healthy Individuals.

PURPOSE: Some individuals with chronic pain find daily life sensations (eg, noise, light, or touch) aversive. This amplification of multisensory sensations has been associated with centrally mediated plasticity; for example, greater multisensory sensitivity (MSS) occurs in patients with fibromyalgia than rheumatoid arthritis. However, whether MSS preferentially relates to pain measures which reflect central influences (eg, dynamic quantitative sensory testing (QST) or referred pain), or whether the MSS-pain relationship requires priming from chronic pain, is unknown. Thus, this cross-sectional study investigated the relationships between MSS assessed in a pain-free state and evoked pain sensitivity. METHODS: Experimental intramuscular infusion pain and multiple static and dynamic QST were assessed in 465 healthy, pain-free adults: pain thresholds using pressure (PPTs) and heat (HPTs), temporal summation of pain (TSP) using pressure, heat or punctate stimuli, and conditioned pain modulation (CPM) using pressure or heat test stimuli. MSS was assessed using 7 items from Barsky's Somatosensory Amplification Scale. Differences in pain and QST between sex-specific MSS quartiles were assessed, adjusting for multiple comparisons. All participants completed at least one intramuscular infusion condition, but not all were asked to complete each QST (n=166-465). RESULTS: Both static and dynamic QST differed between highest and lowest MSS quartiles using pressure stimuli: lower PPTs (adjusted-p<0.01); increased pressure TSP (adjusted-p=0.02); lower pressure CPM (adjusted-p=0.01). However, none of the heat or punctate QST measures (HPTs, TSP, or CPM) differed between MSS quartiles (adjusted-p>0.05). Odds of experiencing TSP or referred pain was not greater, whereas CPM was 8-fold less likely, in those with highest MSS. CONCLUSION: Normal variation in non-noxious MSS is related to both static and dynamic pain sensitivity, without sensitization associated with chronic pain, but is dependent on the QST stimulus. Thus, common influences on MSS and pain sensitivity may involve central mechanisms but are likely more complex than previously recognized.

Adapting a fatigue model for shoulder flexion fatigue: Enhancing recovery rate during intermittent rest intervals.

Although the rotator cuff muscles are susceptible to fatigue, shoulder fatigue studies reporting torque decline during intermittent tasks are relatively uncommon in the literature. A previous modification to the three-compartment controller (3CC) fatigue model incorporated a rest recovery multiplier (3CC-r model) to represent augmented blood flow to muscle during rest intervals (Looft et al., 2018). A rest recovery value of r = 15 was optimal for ankle, knee, and elbow joint regions, whereas r = 30 was better for hand/grip muscles. However, shoulder torque decline data was unavailable in the literature for comparison. Thus, the purpose of this study was to collect fatigue data for two different intermittent, isometric shoulder flexion fatiguing tasks and assess the 3CC-r model with r = 15 or 30 compared to the original 3CC model. Twenty healthy participants (9 M) completed two fatigue tasks: 50% maximum voluntary contraction (MVC) with 50% duty cycle (DC) and 70% MVC with 70% DC. MVCs were assessed at discrete time points (1, 3, 5, 10, and 15 min) until endurance time (MET). Mean observed percent torque decline (%TD) for the two tasks were compared to three model estimates: 3CC-r (using r = 15 and r = 30) and 3CC. Using these data, we confirmed that the addition of a rest multiplier (r = 15 somewhat better than r = 30) substantially improved predictions of shoulder fatigue using a previously validated analytical fatigue model (3CC). The relatively large reduction in model errors over the original model suggests the importance of representing augmented recovery during rest periods.

The interaction between pain and movement.

STUDY DESIGN: Clinical commentary. INTRODUCTION/PURPOSE: Pain and movement are universally relevant phenomena that influence human experiences in readily observable ways. Improved understanding of pain-movement relationships can guide medical and rehabilitative approaches to recovery and decrease risk of dysfunctional long-term consequences of otherwise normal neuromuscular responses. Therefore, the overall intent of this article is to elucidate the relationships between pain and movement as they relate to clinical decision making. CONCLUSIONS: Motor output is highly adaptable, can be influenced by multiple mechanisms at various levels along the nervous system, and may vary between individuals despite similar diagnoses. Therefore, interventions need to be individualized and consider both the types of motor response observed (ie, whether the response is protective or maladaptive), and the patient's acute physical activity tolerance when prescribing exercise/movement.

Physical activity is related to function and fatigue but not pain in women with fibromyalgia: baseline analyses from the Fibromyalgia Activity Study with TENS (FAST).

BACKGROUND: Although exercise is an effective treatment for fibromyalgia, the relationships between lifestyle physical activity and multiple symptomology domains of fibromyalgia are not clear. Thus, the purpose of this study was to comprehensively examine the relationships between lifestyle physical activity with multiple outcome domains in women with fibromyalgia, including pain, fatigue, function, pain-related psychological constructs, and quality of life. METHODS: Women (N = 171), aged 20 to 70 years, diagnosed with fibromyalgia, recruited from an ongoing two-site clinical trial were included in this prespecified subgroup analysis of baseline data. Physical activity was assessed using self-report and accelerometry. Symptomology was assessed using questionnaires of perceived physical function, quality of life, fatigue, pain intensity and interference, disease impact, pain catastrophizing, and fear of movement. In addition, quantitative sensory testing of pain sensitivity and performance-based physical function were assessed. Correlation coefficients, regression analyses and between-group differences in symptomology by activity level were assessed, controlling for age and body mass index (BMI). RESULTS: Lifestyle physical activity was most closely associated with select measures of physical function and fatigue, regardless of age and BMI. Those who performed the lowest levels of lifestyle physical activity had poorer functional outcomes and greater fatigue than those with higher physical activity participation. No relationships between lifestyle physical activity and pain, pain sensitivity, or pain-related psychological constructs were observed. CONCLUSIONS: Lifestyle physical activity is not equally related to all aspects of fibromyalgia symptomology. Lifestyle physical activity levels have the strongest correlations with function, physical quality of life, and movement fatigue in women with fibromyalgia. No relationships between lifestyle physical activity and pain, pain sensitivity, or psychological constructs were observed. These data suggest that physical activity levels are more likely to affect function and fatigue, but have negligible relationships with pain and pain-related psychological constructs, in women with fibromyalgia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01888640 . Registered on 28 June 2013.

A Mechanism-Based Approach to Physical Therapist Management of Pain.

Pain reduction is a primary goal of physical therapy for patients who present with acute or persistent pain conditions. The purpose of this review is to describe a mechanism-based approach to physical therapy pain management. It is increasingly clear that patients need to be evaluated for changes in peripheral tissues and nociceptors, neuropathic pain signs and symptoms, reduced central inhibition and enhanced central excitability, psychosocial factors, and alterations of the movement system. In this Perspective, 5 categories of pain mechanisms (nociceptive, central, neuropathic, psychosocial, and movement system) are defined, and principles on how to evaluate signs and symptoms for each mechanism are provided. In addition, the underlying mechanisms targeted by common physical therapist treatments and how they affect each of the 5 categories are described. Several different mechanisms can simultaneously contribute to a patient's pain; alternatively, 1 or 2 primary mechanisms may cause a patient's pain. Further, within a single pain mechanism, there are likely many possible subgroups. For example, reduced central inhibition does not necessarily correlate with enhanced central excitability. To individualize care, common physical therapist interventions, such as education, exercise, manual therapy, and transcutaneous electrical nerve stimulation, can be used to target specific pain mechanisms. Although the evidence elucidating these pain mechanisms will continue to evolve, the approach outlined here provides a conceptual framework for applying new knowledge as advances are made.

Lab-based validation of different data processing methods for wrist-worn ActiGraph accelerometers in young adults.

The wrist is increasingly being used as the preferred site for objectively assessing physical activity but the relative accuracy of processing methods for wrist data has not been determined. OBJECTIVE: This study evaluates the validity of four processing methods for wrist-worn ActiGraph (AG) data against energy expenditure (EE) measured using a portable metabolic analyzer (OM; Oxycon mobile) and the Compendium of physical activity. APPROACH: Fifty-one adults (ages 18-40) completed 15 activities ranging from sedentary to vigorous in a laboratory setting while wearing an AG and the OM. Estimates of EE and categorization of activity intensity were obtained from the AG using a linear method based on Hildebrand cutpoints (HLM), a non-linear modification of this method (HNLM), and two methods developed by Staudenmayer based on a Linear Model (SLM) and using random forest (SRF). Estimated EE and classification accuracy were compared to the OM and Compendium using Bland-Altman plots, equivalence testing, mean absolute percent error (MAPE), and Kappa statistics. MAIN RESULTS: Overall, classification agreement with the Compendium was similar across methods ranging from a Kappa of 0.46 (HLM) to 0.54 (HNLM). However, specificity and sensitivity varied by method and intensity, ranging from a sensitivity of 0% (HLM for sedentary) to a specificity of ~99% for all methods for vigorous. None of the methods was significantly equivalent to the OM (p > 0.05). SIGNIFICANCE: Across activities, none of the methods evaluated had a high level of agreement with criterion measures. Additional research is needed to further refine the accuracy of processing wrist-worn accelerometer data.

The Effect of Widespread Pain on Knee Pain Worsening, Incident Knee Osteoarthritis (OA), and Incident Knee Pain: The Multicenter OA (MOST) Study.

OBJECTIVE: Whether widespread pain (WSP) affects the risk of developing knee pain or knee osteoarthritis (OA) is unknown and could enhance understanding of pain mechanisms in OA. METHODS: Subjects from the Multicenter OA (MOST) study, a US National Institutes of Health-funded prospective cohort of older adults with or at risk of knee OA, were characterized regarding WSP, defined as pain above and below the waist on both sides of the body and axially using a standard homunculus, excluding knee pain at 60 months (baseline). Followup occurred 2 years later. We assessed the relation of WSP to odds of knee pain worsening (≥ 2-point increase in the Western Ontario and McMaster Universities Arthritis Index pain subscale) using logistic regression, and to odds of incident radiographic knee OA (ROA; Kellgren-Lawrence arthritis scale ≥ grade 2 of either knee among those free of ROA at baseline) and incident consistent frequent knee pain (CFKP; knee pain on most days during the past month among participants free of knee pain at baseline) in 1 or both knees using multinomial regression adjusting for potential confounders. RESULTS: There were 1752 participants available for analysis [mean age (SD) 67.0 yrs (7.7), body mass index 30.5 kg/m2 (5.9), 59% women]. Baseline presence of WSP was not associated with worsened knee pain (adjusted OR 1.15, 95% CI 0.89-1.48, p = 0.30), ROA (adjusted OR 0.86, 95% CI 0.46-1.63, p = 0.65), or incident CFKP (adjusted OR 1.69, 95% CI 0.96-2.96, p = 0.07). CONCLUSION: WSP was not significantly associated with worsening knee pain, incident ROA, or CFKP. Development of knee pain and ROA does not appear to be influenced by underlying WSP.

Pain sensitivity profiles in patients with advanced knee osteoarthritis.

The development of patient profiles to subgroup individuals on a variety of variables has gained attention as a potential means to better inform clinical decision making. Patterns of pain sensitivity response specific to quantitative sensory testing (QST) modality have been demonstrated in healthy subjects. It has not been determined whether these patterns persist in a knee osteoarthritis population. In a sample of 218 participants, 19 QST measures along with pain, psychological factors, self-reported function, and quality of life were assessed before total knee arthroplasty. Component analysis was used to identify commonalities across the 19 QST assessments to produce standardized pain sensitivity factors. Cluster analysis then grouped individuals who exhibited similar patterns of standardized pain sensitivity component scores. The QST resulted in 4 pain sensitivity components: heat, punctate, temporal summation, and pressure. Cluster analysis resulted in 5 pain sensitivity profiles: a "low pressure pain" group, an "average pain" group, and 3 "high pain" sensitivity groups who were sensitive to different modalities (punctate, heat, and temporal summation). Pain and function differed between pain sensitivity profiles, along with sex distribution; however, no differences in osteoarthritis grade, medication use, or psychological traits were found. Residualizing QST data by age and sex resulted in similar components and pain sensitivity profiles. Furthermore, these profiles are surprisingly similar to those reported in healthy populations, which suggests that individual differences in pain sensitivity are a robust finding even in an older population with significant disease.

Perceived function and physical performance are associated with pain and fatigue in women with fibromyalgia.

BACKGROUND: Fibromyalgia is a condition characterized by chronic widespread muscle pain and fatigue and associated with significant impairment in perceived function and reduced physical performance. The purpose of this study was to determine the degree to which pain and fatigue are associated with perceived function and physical performance in women with fibromyalgia. METHODS: Hierarchical linear regression determined the contribution of pain and fatigue (Numeric Rating Scale (NRS) for resting, movement and combined) to perceived function (Fibromyalgia Impact Questionnaire Revised - Function Subscale, FIQR-Function), Multidimensional Assessment of Fatigue - Activities of Daily Living (MAF-ADL) and SF-36 Physical Function Subscale (SF-36-PF) and physical performance (6-Minute Walk Test, 6MWT and Five Time Sit To Stand, 5TSTS) while controlling for age, body mass index, pain catastrophizing, fear of movement, anxiety, and depression in women with fibromyalgia (N = 94). RESULTS: For perceived function, movement pain and movement fatigue together better predicted FIQR-function (adjusted R(2) = 0.42, p ≤ 0.001); MAF-ADL (adjusted R(2) = 0.41, p ≤ 0.001); and SF-36-PF function (adjusted R(2) = 0.34, p ≤ 0.001). For physical performance measures, movement pain and fatigue together predicted 6MWT distance (adjusted R(2) = 0.42, p ≤ 0.001) and movement fatigue alone predicted performance time on the 5TSTS (adjusted R(2) = 0.20, p ≤ 0.001). CONCLUSIONS: Pain and fatigue are significantly associated with and explain more than one-third of the variance in perceived function and physical performance in women with fibromyalgia. TRIAL REGISTRATION: NIH Clinicaltrials.gov REGISTRATION: NCT01888640 . Registered 13 June 2013.

Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala.

Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative "pain matrix" that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient's expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a "pain matrix" and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient's heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain's conscious experience.