Associations of pain catastrophizing with pain-related brain structure in individuals with or at risk for knee osteoarthritis: Sociodemographic considerations.

Compelling evidence exists that non-Hispanic blacks (NHB) engage in pain catastrophizing (negatively evaluate one's ability to cope with pain) more often than non-Hispanic whites (NHW). Functional neuroimaging studies revealed that individuals with high levels of trait pain catastrophizing show increased cerebral responses to pain in several pain-related brain regions (e.g., insula, primary somatosensory cortex [S1]), but associations between brain structure and catastrophizing remain largely unexplored. The current investigation was conducted at the University of Florida and the University of Alabama at Birmingham. Participants were 129 community-dwelling adults with or at risk of knee osteoarthritis (OA). Participants completed the pain catastrophizing subscale of the Coping Strategies Questionnaire-Revised and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain intensity subscale. Magnetic Resonance Imaging data were obtained. MANOVA and Chi-Square analyses assessed sociodemographic/clinical differences stratified by ethnicity/race. Multivariate regression analyses with insula and somatosensory cortical thickness entered as dependent variables with catastrophizing and the interaction between catastrophizing and ethnicity/race as the independent variables. Covariates include education, body mass index, study site, and WOMAC pain (ethnicity/race was an additional covariate in non-stratified analyses). There were significant interactions between ethnicity/race, pain catastrophizing, and brain structure. Higher pain catastrophizing was associated with thinner S1 bilaterally (ps < .05) in NHW, but not NHB participants with or at risk for knee OA. These results suggest that pain catastrophizing might have differing effects on pain-related central pathways and may contribute to ethnic/race group differences in individuals with or at risk for knee OA.

Everyday Discrimination in Adults with Knee Pain: The Role of Perceived Stress and Pain Catastrophizing.

PURPOSE: Research indicates pain-related disparities in the impact of knee osteoarthritis (OA) across both sex and ethnicity/race. While several factors likely contribute to these disparities, experiences of discrimination are associated with poor OA-related pain, disability, and functional performance. However, the mechanisms that mediate experiences of discrimination and OA-related outcomes are unclear. The current cross-sectional study examined the associations between everyday experiences of discrimination and clinical pain, disability and functional performance among non-Hispanic Black (NHB) and non-Hispanic White (NHW) persons with or at risk of knee OA and assessed the serial mediated model of perceived stress and pain catastrophizing on these relationships in women only. PATIENTS AND METHODS: Participants were 188 community-dwelling adults who presented with unilateral or bilateral knee pain and screened positive for clinical knee pain. Participants completed several measures including experiences of discrimination, Perceived Stress Scale, Coping Strategies Questionnaire-Revised (CSQ-R): Pain Catastrophizing subscale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Graded Chronic Pain Scale (GCPS), and Short Physical Performance Battery (SPPB). RESULTS: As compared to NHW participants, NHB individuals reported experiencing significantly higher levels of discrimination (F(1, 175)=26.660, p<0.001), greater levels of pain catastrophizing (F(1, 180)=12.919, p<0.001), higher levels of clinical pain and disability, and lower levels of physical function (ps<0.05). However, perceived stress was positively correlated with discrimination in the NHW group only (NHW females: r=0.40, p<0.01; NHW males: r=0.37, p<0.05). Further, perceived stress and pain catastrophizing mediated the relationship between discrimination and outcome variables (WOMAC pain, GCPS interference [pain disability], and SPPB function) in female participants after controlling for relevant sociodemographic variables (study site, age, race, income, and body mass index). CONCLUSION: These results may have implications for the treatment of perceived stress and catastrophizing as a means to reduce the negative impact of experiences of discrimination on the experience of chronic pain, particularly for women.

Psychological Predictors of Perceived Age and Chronic Pain Impact in Individuals With and Without Knee Osteoarthritis.

OBJECTIVE: Chronological age is a risk factor in chronic pain; however, aging research supports the premise that physical and psychological health may better predict perceived age. Given the lack of evidence on perceived age in the context of chronic pain, the current study presents novel findings about the relationship between perceived age, chronic pain impact, and psychological function in adults with and without knee osteoarthritis. METHODS: This secondary analysis was part of an ongoing multisite observational cohort study to understand the progression of knee pain and disability. Community-dwelling adults (N=227) ages 45+ completed measures of trait resilience, trait positive and negative affect, pain catastrophizing, subjective perceptions of age, and the Graded Chronic Pain Scale. RESULTS: On average, participants reported feeling 10 years younger than their chronological age; however, this effect was attenuated in individuals reporting high-impact pain. Lower perceived age was associated with lower pain impact (low pain/low disability), while higher perceived age correlated with higher pain impact (high pain/high disability) and more adverse psychological effects. Using hierarchical linear regression, high-impact pain and positive affect emerged as statistically significant predictors of perceived age, whereas no differences were observed among trait resilience, negative affect, or pain catastrophizing. DISCUSSION: These findings highlight the importance of a biopsychosocial approach in understanding the intersection between psychological and physical factors associated with chronic pain. Addressing negative self-perceptions of aging, while simultaneously augmenting positive affect, through psychological therapies may mitigate pain and disability.

Neuropathic-Like Pain Symptoms in a Community-Dwelling Sample with or at Risk for Knee Osteoarthritis.

OBJECTIVE: To characterize neuropathic-like pain among individuals with or at risk for knee osteoarthritis. SUBJECTS: One hundred eighty-four individuals who self-identified as non-Hispanic black or non-Hispanic white and presented with unilateral or bilateral knee pain. DESIGN: Neuropathic-like pain was assessed using the painDETECT, and those with high vs low neuropathic-like pain were compared on clinical pain, psychological symptoms, physical function, and quantitative sensory testing. Analyses were unadjusted, partially and fully adjusted for relevant covariates. RESULTS: Thirty-two (17.4%) participants reported experiencing neuropathic-like pain features above the painDETECT clinical cut-score. The neuropathic-like pain group reported significantly greater pain severity on all measures of clinical pain and higher levels of psychological symptoms when fully adjusted for covariates, but no differences emerged for disability and lower extremity function. The neuropathic-like pain group also reported greater overall heat pain ratings during the heat pain threshold and increased temporal summation of heat pain in the fully adjusted model. Additionally, those with neuropathic-like pain symptoms reported greater painful after-sensations following heat pain temporal summation in all analyses. No significant group differences in pressure pain threshold emerged at any of the testing sites. In contrast, temporal summation of mechanical pain was significantly greater at both the index knee and the ipsilateral hand for the neuropathic-like pain group in all analyses. CONCLUSIONS: Participants with or at risk for knee osteoarthritis who reported high neuropathic-like pain experienced significantly greater clinical pain and increased heat and mechanical temporal summation at the index knee and other body sites tested, suggesting central sensitization.

Race/Ethnicity Moderates the Association Between Psychosocial Resilience and Movement-Evoked Pain in Knee Osteoarthritis.

OBJECTIVE: Racial/ethnic disparities in pain are well-recognized, with non-Hispanic blacks (NHBs) experiencing greater pain severity and pain-related disability than non-Hispanic whites (NHWs). Although numerous risk factors are posited as contributors to these disparities, there is limited research addressing how resilience differentially influences pain and functioning across race/ethnicity. Therefore, this study examined associations between measures of psychosocial resilience, clinical pain, and functional performance among adults with knee osteoarthritis (OA), and assessed the moderating role of race/ethnicity on these relationships. METHODS: In a secondary analysis of the Understanding Pain and Limitations in Osteoarthritic Disease (UPLOAD-2) study, 201 individuals with knee OA (NHB = 105, NHW = 96) completed measures of resilience (ie, trait resilience, optimism, positive well-being, social support, positive affect) and clinical pain, as well as a performance-based measure assessing lower-extremity function and movement-evoked pain. RESULTS: Bivariate analyses showed that higher levels of psychosocial resilience were associated with lower clinical pain and disability and more optimal physical functioning. NHBs reported greater pain and disability, poorer lower-extremity function, and higher movement-evoked pain compared with NHWs; however, measures of psychosocial resilience were similar across race/ethnicity. In moderation analyses, higher optimism and positive well-being were protective against movement-evoked pain in NHBs, whereas higher levels of positive affect were associated with greater movement-evoked pain in NHWs. CONCLUSION: Our findings underscore the importance of psychosocial resilience on OA-related pain and function and highlight the influence of race/ethnicity on the resilience-pain relationship. Treatments aimed at targeting resilience may help mitigate racial/ethnic disparities in pain.

At the Intersection of Ethnicity/Race and Poverty: Knee Pain and Physical Function.

BACKGROUND: Knee osteoarthritis (OA) disproportionately affects racial and ethnic minorities. Non-Hispanic Blacks (NHB) report a higher prevalence and severity of knee OA symptoms than their non-Hispanic White (NHW) counterparts. The role of poverty in explaining this disparity remains unclear. OBJECTIVE: The overall aim of this cross-sectional study was to determine whether ethnic/racial differences in knee pain and physical function varied according to poverty status. DESIGN: NHB and NHW adults with or at risk of knee OA self-reported sociodemographic information, and completed the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) and the Short Physical Performance Battery (SPPB). Annual income was adjusted for number of household occupants to determine poverty status (i.e., living above versus below poverty line). RESULTS: Findings revealed 120 individuals living above the poverty line (49% NHB, 77% NHW) and 71 individuals living below the poverty line (51% NHB, 23% NHW). Adjusted multivariable models revealed significant ethnic/race by poverty status interactions for knee pain (p = 0.036) and physical function (p = 0.032) on the WOMAC, as well as physical function on the SPPB (p = 0.042). Post hoc contrasts generally revealed that NHW adults living above the poverty line experienced the least severe knee pain and best physical function, while NHB adults living below the poverty line experienced the most severe knee pain and poorest physical function. CONCLUSIONS: Results of the present study add to the literature by emphasizing the importance of considering poverty and/or other indicators of socioeconomic status in studies examining ethnic/racial disparities in pain and physical function.

Resilience factors may buffer cellular aging in individuals with and without chronic knee pain.

Telomere length, a measure of cellular aging, is inversely associated with chronic pain severity. While psychological resilience factors (e.g., optimism, acceptance, positive affect, and active coping) are associated with lower levels of clinical pain and greater physical functioning, it is unknown whether resilience may buffer against telomere shortening in individuals with chronic pain. Additionally, a broader conceptualization of resilience that includes social and biobehavioral factors may improve our understanding of the relationship between resilience, chronic pain, and health outcomes. In individuals with and without chronic knee pain, we investigated whether (1) psychological resilience would be positively associated with telomere length and if (2) a broader conceptualization of resilience including social and biobehavioral factors would strengthen the association. Seventy-nine adults, 45 to 85 years of age, with and without knee pain completed demographic, health, clinical pain, psychological, social, and biobehavioral questionnaires. Resilience levels were determined by summing the total number of measures indicating resilience based on published clinical ranges and norms. Blood samples were collected, and telomere length was determined. In regression analyses controlling for sex, race, age, and characteristic pain intensity, greater psychological resilience and psychosocial/biobehavioral resilience were associated with longer telomeres ( p = .0295 and p = .0116, respectively). When compared, psychosocial/biobehavioral resilience was significantly more predictive of telomere length than psychological resilience ( p < .0001). Findings are promising and encourage further investigations to enhance understanding of the biological interface of psychosocial and biobehavioral resilience factors in individuals with musculoskeletal chronic pain conditions.

Optimism and Psychological Resilience are Beneficially Associated With Measures of Clinical and Experimental Pain in Adults With or at Risk for Knee Osteoarthritis.

OBJECTIVES: This cross-sectional study examined the associations among optimism, psychological resilience, endogenous pain inhibition, and clinical knee pain severity. Two hypotheses were tested. First, we hypothesized that experimentally tested endogenous pain inhibition would mediate the relationship between optimism and clinical knee pain severity. Second, it was also hypothesized that optimism would moderate the relationships of psychological resilience with endogenous pain inhibition and clinical knee pain severity, particularly for individuals with high optimism. METHODS: A total of 150 individuals with or at risk for symptomatic knee osteoarthritis completed the Life Orientation Test-Revised, the Brief Resilience Scale, and the revised Short-Form McGill Pain Questionnaire-2 to assess optimism, psychological resilience, and clinical knee pain severity, respectively. Endogenous pain inhibition was examined experimentally using a conditioned pain modulation (CPM) protocol with algometry (test stimulus) and a cold pressor task (conditioning stimulus). RESULTS: As hypothesized, results showed that increased CPM significantly mediated the association between higher optimism and lower clinical knee pain severity. Further, optimism moderated the association between psychological resilience and CPM. However, contrary to our hypothesis, greater psychological resilience was associated with enhanced CPM in individuals with low optimism only. DISCUSSION: This study suggests that an optimistic outlook may beneficially impact clinical pain severity by altering endogenous pain modulatory capacity. Furthermore, individuals with low optimism (ie, pessimists) may be more adept at engaging resources that promote psychological resilience, which in turn, enhances endogenous pain modulatory capacity. Therefore, this study supports consideration of psychological resilience factors when evaluating experimental and clinical pain outcomes.

Omega-6: Omega-3 PUFA Ratio, Pain, Functioning, and Distress in Adults With Knee Pain.

OBJECTIVES: Osteoarthritis (OA) is associated with inflammation, chronic pain, functional limitations, and psychosocial distress. High omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are associated with lower levels of inflammatory mediators, anti-nociception, and adaptive cognitive/emotional functioning. High omega-6 (n-6) PUFAs are associated with inflammation, nociception, and psychological distress. While findings related to n-3 supplementation in knee OA are mixed, consideration of the n-6:n-3 ratio and additional outcome measures may provide improved understanding of the potential relevance of these fatty acids in OA. On the basis of recommended and typical ranges of the n-6:n-3 ratio, we hypothesized that in adults with knee pain, those with a high n-6:n-3 ratio would have greater pain/functional limitations, experimental pain sensitivity, and psychosocial distress compared with those with a low n-6:n-3 ratio. MATERIALS AND METHODS: A cross-sectional investigation of clinical and experimental pain and physical and psychosocial functioning was completed in 167 adults ages 45 to 85 meeting knee OA screening criteria. Blood samples were collected and the plasma n-6:n-3 PUFA ratio determined. Quartile splits were computed and low (n=42) and high (n=41) ratio groups were compared. RESULTS: The high ratio group reported greater pain and functional limitations, (all Ps<0.04), mechanical temporal summation (hand and knee, P<0.05), and perceived stress (P=0.008) but not depressive symptoms. DISCUSSION: In adults with knee pain, a high n-6:n-3 ratio is associated with greater clinical pain/functional limitations, experimental pain sensitivity, and psychosocial distress compared with a low ratio group. Findings support consideration of the n-6:n-3 PUFA ratio and additional clinical endpoints in future research efforts.

Physical performance and movement-evoked pain profiles in community-dwelling individuals at risk for knee osteoarthritis.

BACKGROUND: Knee pain associated with osteoarthritis is a significant contributor to decreased physical function. Recent evidence supports the inter-individual heterogeneity associated with knee pain presentation, but whether there is similar heterogeneity in physical performance among these individuals has not been previously examined. The aim of the present study was to characterize the variability in physical performance profiles and the pain evoked by their performance (i.e., movement-evoked pain). METHODS: In a secondary analysis of the community-based study Understanding Pain and Limitations in Osteoarthritic Disease (UPLOAD), individuals (n=270) completed functional, pain, psychological, and somatosensory assessments. Hierarchical cluster analysis was used to derive physical function profiles that were subsequently compared across several clinical, psychological and experimental pain measures. RESULTS: Our results support the hypothesis that among persons with knee OA pain, three different physical performance profiles exist with varying degrees of movement-evoked pain. Even as all three groups experienced moderate to severe levels of spontaneous knee pain, those individuals with the most severe movement-evoked pain and lowest physical functional performance also had the least favorable psychological characteristics along with increased mechanical pain sensitivity and temporal summation. CONCLUSIONS: Our findings support the need for the assessment and consideration of movement-evoked pain during physical performance tasks as these have the potential to increase the value of functional and pain assessments clinically. The identification of the mechanisms driving pain burden within homogeneous groups of individuals will ultimately allow for targeted implementation of treatments consistent with a biopsychosocial model of pain.

Single Nucleotide Polymorphism in the COL11A2 Gene Associated with Heat Pain Sensitivity in Knee Osteoarthritis.

Abstract: Pain is one of the most prominent symptoms of osteoarthritis. However, there is often discordance between the pain experienced by individuals with osteoarthritis and the degree of articular pathology. This suggests that individual differences, including genetic variability in the central processing of nociceptive stimuli, may impact the presentation of osteoarthritis. Here, we show that the single nucleotide polymorphism rs16868943 in the collagen gene COL11A2 is significantly associated with lowered heat pain tolerance on the arm in participants with knee osteoarthritis (P = 1.21 × 10−6, P = 0.0053 after Bonferroni correction, beta = −3.42). A total of 161 knee osteoarthritis participants were included and evaluated for heat, punctate and pressure pain sensitivity of the affected knee and the ipsilateral arm. Each participant was genotyped for 4392 single nucleotide polymorphisms in genes implicated in pain perception, inflammation and mood and tested for association with pain sensitivity. The minor A allele of single nucleotide polymorphism rs16868943 was significantly associated with lower arm heat pain tolerance after correction for age, gender, race, and study site. This single nucleotide polymorphism was also nominally associated with other measures of heat pain sensitivity, including lowered knee heat pain tolerance (P = 1.14 × 10−5, P = 0.05 after Bonferroni correction), lowered arm heat pain threshold (P = 0.0039, uncorrected) and lowered knee heat pain threshold (P = 0.003, uncorrected). Addition of genotypes from 91 participants without knee pain produced a significant interaction between knee osteoarthritis status and the rs16868943 single nucleotide polymorphism in heat pain tolerance (P = 1.71 × 10−5), such that rs16868943 was not associated with heat pain tolerance in participants without knee pain (P = 0.12, beta = 1.3). This is the first study to show genetic association with heat pain tolerance in individuals with osteoarthritis. The association is specific to participants who have already developed knee osteoarthritis, suggesting that the COL11A2 gene, which has previously been associated with familial osteoarthritis, may play a role in pain sensitization after the development of osteoarthritis.

Ethnicity, Cortisol, and Experimental Pain Responses Among Persons With Symptomatic Knee Osteoarthritis.

OBJECTIVES: Although several factors are known to contribute to ethnic differences in pain, relatively little attention has been devoted to physiological factors. Our first aim was to examine the relationship between cortisol and pain responses during a cold-pressor task (CPT) among African American (AA) and non-Hispanic White (NHW) adults with knee osteoarthritis (OA). Our second aim was to assess the relationship between perceived racial discrimination and cortisol among AA participants. MATERIALS AND METHODS: Participants were 91 (56 AA; 35 NHW) community-dwelling adults between the ages of 45 to 85 with knee OA based upon the American College of Rheumatology clinical criteria. Plasma cortisol was measured at 3 timepoints: (1) baseline, (2) before the CPT, and (3) 20 minutes following the CPT. Perceived racial discrimination was measured by the Experiences of Discrimination scale. RESULTS: Using linear regression, we found a significant interaction between ethnicity and cortisol before the CPT with pain intensity ratings (ß=-0.26; P=0.02). Analysis of simple slopes revealed that cortisol concentrations were negatively associated with pain intensity ratings in NHW participants (ß=-0.54; P=0.001), but not in AA participants (ß=-0.15; P=0.26). Perceived racial discrimination was not related to cortisol concentrations or pain ratings. DISCUSSION: Consistent with previous findings in young healthy adults, cold-pressor pain responses are related to pre-CPT cortisol concentrations in NHW persons with knee OA but not in their AA counterparts. Additional studies are required to better understand this finding.

Accelerated aging in adults with knee osteoarthritis pain: consideration for frequency, intensity, time, and total pain sites.

INTRODUCTION: Individuals with osteoarthritis (OA) show increased morbidity and mortality. Telomere length, a measure of cellular aging, predicts increased morbidity and mortality. Telomeres shorten with persisting biological and psychosocial stress. Living with chronic OA pain is stressful. Previous research exploring telomere length in people with OA has produced inconsistent results. Considering pain severity may clarify the relationship between OA and telomeres. OBJECTIVES: We hypothesized that individuals with high OA chronic pain severity would have shorter telomeres than those with no or low chronic pain severity. METHODS: One hundred thirty-six adults, ages 45 to 85 years old, with and without symptomatic knee OA were included in the analysis. Peripheral blood leukocyte telomere length was measured, and demographic, clinical, and functional data were collected. Participants were categorized into 5 pain severity groups based on an additive index of frequency, intensity, time or duration, and total number of pain sites (FITT). Covariates included age, sex, race or ethnicity, study site, and knee pain status. RESULTS: The no or low chronic pain severity group had significantly longer telomeres compared with the high pain severity group, P = 0.025. A significant chronic pain severity dose response emerged for telomere length, P = 0.034. The FITT chronic pain severity index was highly correlated with the clinical and functional OA pain measures. However, individual clinical and functional measures were not associated with telomere length. CONCLUSION: Results demonstrate accelerated cellular aging with high knee OA chronic pain severity and provide evidence for the potential utility of the FITT chronic pain severity index in capturing the biological burden of chronic pain.

Experimental pain phenotyping in community-dwelling individuals with knee osteoarthritis.

Pain among individuals with knee osteoarthritis (OA) is associated with significant disability in older adults, and recent evidence demonstrates enhanced experimental pain sensitivity. Although previous research showed considerable heterogeneity in the OA clinical pain presentation, less is known regarding the variability in responses to experimental pain. The present study included individuals with knee OA (n = 292) who participated in the Understanding Pain and Limitations in Osteoarthritic Disease study and completed demographic and psychological questionnaires followed by a multimodal quantitative sensory testing (QST) session. Quantitative sensory testing measures were subjected to variable reduction procedures to derive pain sensitivity index scores, which in turn were entered into a cluster analysis. Five clusters were significantly different across all pain sensitivity index variables (P < 0.001) and were characterized by: (1) low pain sensitivity to pressure pain (N = 39); (2) average pain sensitivity across most modalities (N = 88); (3) high temporal summation of punctate pain (N = 38); (4) high cold pain sensitivity (N = 80); and (5) high sensitivity to heat pain and temporal summation of heat pain (N = 41). Clusters differed significantly by race, gender, somatic reactivity, and catastrophizing (P < 0.05). Our findings support the notion that there are distinct subgroups or phenotypes based on experimental pain sensitivity in community-dwelling older adults with knee OA, expanding previous findings of similar cluster characterizations in healthy adults. Future research is needed to further understand the pathophysiological mechanisms underlying pain within these subgroups, which may be of added value in tailoring effective treatments for people with OA.

Minority Aging and Endogenous Pain Facilitatory Processes.

OBJECTIVE: The aim of the current study was to examine the relationships among age, ethnicity, and endogenous pain facilitation using temporal summation (TS) responses to mechanical and heat stimuli. DESIGN: The present study assessed hyperalgesia and pain facilitation to thermal and mechanical stimuli at the knee and distal sites in 98 pain-free men and women. Participants were drawn from two ethnic groups [African-American (AA) and non-Hispanic white (NHW)] and two age groups (19-35 and 45-85). RESULTS: Significant main effects of ethnicity were demonstrated for both mechanical and heat modalities (all P's ≤ 0.05), suggesting that AA participants, relative to NHW counterparts, demonstrated enhanced hyperalgesia. Age differences (older > younger) in hyperalgesia were found in mechanical pain ratings only. Results indicated that mechanical pain ratings significantly increased from first to maximal pain as a function of both age group and ethnicity (all P's ≤ 0.05), and a significant ethnicity by age interaction for TS of mechanical pain was found at the forearm (P < 0.05) and trended toward significance at the knee (P = 0.071). Post-hoc tests suggested that results were primarily driven by the older AA participants, who demonstrated the greatest mechanical TS. Additionally, evidence of differences in heat TS due to both ethnicity alone (all P's ≤ 0.05) and minority aging was also found. CONCLUSIONS: This study provides evidence suggesting that older AAs demonstrate enhanced pain facilitatory processes, which is important because this group may be at increased risk for development of chronic pain. These results underscore the necessity of testing pain modulatory mechanisms when addressing questions related to pain perception and minority aging.

Association of Joint Inflammation With Pain Sensitization in Knee Osteoarthritis: The Multicenter Osteoarthritis Study.

OBJECTIVE: Pain sensitization is associated with pain severity in knee osteoarthritis (OA), but its cause in humans is not well understood. We examined whether inflammation, assessed as synovitis and effusion on magnetic resonance imaging (MRI), or mechanical load, assessed as bone marrow lesions (BMLs), was associated with sensitization in knee OA. METHODS: Subjects in the Multicenter Osteoarthritis Study, a National Institutes of Health-funded cohort of persons with or at risk of knee OA, underwent radiography and MRI of the knee, and standardized quantitative sensory testing (temporal summation and pressure pain threshold [PPT]) of the wrist and patellae at baseline and 2 years later. We examined the relation of synovitis, effusion, and BMLs to temporal summation and PPT cross-sectionally and longitudinally. RESULTS: There were 1,111 subjects in the study sample (mean age 67 years, mean body mass index 30 kg/m(2) , 62% female). Synovitis was associated with a significant decrease in PPT at the patella (i.e., more sensitized) over 2 years (adjusted ß -0.30 [95% confidence interval (95% CI) -0.52, -0.08]). Effusion was similarly associated with a decrease in PPT at the wrist (adjusted ß -0.24 [95% CI -0.41, -0.08]) and with risk of incident temporal summation at the patella (adjusted OR 1.54 [95% CI 1.01, 2.36]). BMLs were not associated with either quantitative sensory testing measure. CONCLUSION: Inflammation, as evidenced by synovitis or effusion, is associated with pain sensitization in knee OA. In contrast, BMLs do not appear to contribute to sensitization in knee OA. Early targeting of inflammation is a reasonable strategy to test for prevention of sensitization and through this, reduction of pain severity, in knee OA.

Enhanced Pain Sensitivity Among Individuals With Symptomatic Knee Osteoarthritis: Potential Sex Differences in Central Sensitization.

OBJECTIVE: Symptomatic knee osteoarthritis (OA) is a condition commonly associated with increased pain, disability, and functional limitations. Given the poor correspondence between radiographic evidence and clinical pain, central sensitization has been implicated as a potential mechanism underlying pain facilitation in knee OA. Sex may be a moderator of centrally mediated changes in knee OA pain; however, few studies have systematically assessed this. Therefore, the aim of this study was to examine differences in peripheral and central sensitization in men and women with symptomatic knee OA, as well as to determine whether these differences vary across age (middle age versus older age). METHODS: Participants (n = 288) between the ages of 45 and 85 years completed a battery of quantitative sensory pain procedures assessing sensitivity to contact heat, cold pressor, mechanical pressure, and punctate stimuli. Differences in temporal summation (TS) were examined, as well as measures of clinical pain and functional performance. RESULTS: When compared to men, women exhibited greater sensitivity to multiple pain modalities (i.e., lower heat, cold, pressure thresholds/tolerances, greater TS of pain); however, there were no sex differences in clinical pain, with the exception of greater widespread pain observed in women. Although there were select age-related differences in pain sensitivity, sex differences in pain varied minimally across the age cohort. CONCLUSION: Overall, these findings provide evidence for greater overall sensitivity to experimental pain in women with symptomatic knee OA compared to men, suggesting that enhanced central sensitivity may be an important contributor to pain in this group.

Disrupted sleep is associated with altered pain processing by sex and ethnicity in knee osteoarthritis.

UNLABELLED: Studies indicate that improving sleep decreases reported pain in patients with knee osteoarthritis, but it is unclear if this association extends to experimentally induced pain responses. A community-based sample of 88 African American and 52 non-Hispanic white adults (45-76 years) with knee osteoarthritis completed the Insomnia Severity Index and the arousal subscale of the Sleep Hygiene and Practices Scale. Participants underwent quantitative sensory testing, including measures of pain sensitivity and facilitation at the knee, and pain inhibition. Outcomes were analyzed with multiple Tobit hierarchical regression models, with adjustment for relevant covariates. Ethnicity and sex by sleep interactions were also entered into the models. After covariate adjustment, main associations were not observed. However, sex interacted with insomnia severity to predict greater temporal summation of heat and punctate pressure pain among women and lower heat temporal summation among men. Men and women who engaged in frequent arousal-associated sleep behaviors demonstrated higher and lower heat temporal summation, respectively. Non-Hispanic whites with greater insomnia severity displayed lower pressure pain thresholds and pain inhibition. Our findings are the first to demonstrate that disrupted sleep is associated with altered pain processing differentially by sex and ethnicity/race among people with knee osteoarthritis. PERSPECTIVE: This article presents the association between insomnia severity, maladaptive sleep behaviors, and experimentally induced pain responses among people with knee osteoarthritis. Disrupted sleep was associated with altered pain processing by sex and ethnicity/race. Offering sleep interventions may help ameliorate pain, but treatment may need to be tailored by sex and ethnicity/race.

A Cross-sectional Examination of Vitamin D, Obesity, and Measures of Pain and Function in Middle-aged and Older Adults With Knee Osteoarthritis.

OBJECTIVES: The prevalence of knee osteoarthritis (OA) is increasing with the aging population and is exacerbated by the growing numbers of obese older adults. Low levels of vitamin D, measured by serum 25-hydroxyvitamin D (25(OH)D), in older adults and obese individuals are correlated with several negative health conditions, including chronic pain. This cross-sectional study sought to examine the interactive influence of 25(OH)D levels and obesity on knee OA pain and functional performance measures. METHODS: The sample consisted of 256 (63% female) racially diverse (55% black/African Americans) middle-aged and older adults (mean age 56.8 y). Blood was collected for analysis of 25(OH)D by high-performance liquid chromatography. Participants provided self-report regarding knee OA pain and underwent a lower extremity functional performance test. RESULTS: Results demonstrated that obesity was associated with lower levels of 25(OH)D. Participants with adequate 25(OH)D levels reported significantly less knee OA pain compared with participants with deficient or insufficient levels, regardless of obesity status. Furthermore, there was a significant interaction between obesity and 25(OH)D levels for lower extremity functional performance, such that obese individuals with adequate 25(OH)D levels demonstrated better performance than those obese participants with deficient or insufficient 25(OH)D levels. DISCUSSION: The mechanisms by which adequate 25(OH)D levels are associated with pain severity and improved function have not been completely elucidated. It may be that the pleiotropic role of biologically active 25(OH)D influences pain and pain processing through peripheral and central mechanisms. Alternatively, higher levels of pain may lead to reduced outdoor activity, which may contribute to both obesity and decreased vitamin D. Thus, investigating vitamin D status in obese and nonobese individuals with knee OA warrants further study.

Benzodiazepine (BZD) use in community-dwelling older adults: Longitudinal associations with mobility, functioning, and pain.

The aim of the study was to determine the prospective association between baseline BZD use and mobility, functioning, and pain among urban and rural African-American and non-Hispanic white community-dwelling older adults. From 1999 to 2001, a cohort of 1000 community-dwelling adults, aged ≥ 65 years, representing a random sample of Medicare beneficiaries, stratified by ethnicity, sex, and urban/rural residence were recruited. BZD use was assessed at an in-home visit. Every six months thereafter, study outcomes were assessed via telephone for 8.5-years. Mobility was assessed with the Life-Space Assessment (LSA). Functioning was quantified with level of difficulty in five basic activities of daily living (ADL: bathing, dressing, transferring, toileting, eating), and six instrumental activities of daily living (IADL: shopping, managing money, preparing meals, light and heavy housework, telephone use). Pain was measured by frequency per week and the magnitude of interference with daily tasks. All analytic models were adjusted for relevant covariates and mental health symptoms. After multivariable adjustment, baseline BZD use was significantly associated with greater difficulty with basic ADL (Estimate=0.39, 95% confidence interval (CI): 0.04-0.74), and more frequent pain (Estimate=0.41, 95%CI: 0.09-0.74) in the total sample and declines in mobility among rural residents (Estimate=-0.67, t(5,902)=-1.98, p=0.048), over 8.5 years. BZD use was prospectively associated with greater risk for basic ADL difficulties and frequent pain among African-American and non-Hispanic white community-dwelling older adults, and life-space mobility declines among rural-dwellers, independently of relevant covariates. These findings highlight the potential long-term negative impact of BZD use among community-dwelling older adults.