Different descending pathways mediate early and late portions of lower limb responses to transcranial magnetic stimulation.

While recent studies in non-human primates have provided evidence that transcranial magnetic stimulation (TMS) activates cells within the reticular formation, it remains unclear whether descending brainstem projections contribute to the generation of TMS-induced motor evoked potentials (MEPs) in skeletal muscles. We compared MEPs in muscles with extensive direct corticomotoneuronal input (first dorsal interosseous) versus a prominent role in postural control (gastrocnemius) to determine whether the amplitude of early and late MEPs were differentially modulated by cortical suppression. Suprathreshold TMS was applied with and without a preceding suprathreshold TMS pulse at two interstimulus intervals (50 and 80 ms). H-reflexes in target muscles were also tested with and without TMS conditioning. Early and late gastrocnemius MEPs were differentially modulated by cortical inhibition, the amplitude of the early MEP being significantly reduced by cortical suppression and the late MEP facilitated. The amplitude of H-reflexes in the gastrocnemius was reduced within the cortical silent period. Early MEPs in the first dorsal interosseous were also reduced during the silent period, but late MEPs unaffected. Independent modulation of early and late MEPs in the gastrocnemius muscle supports the idea that the MEP is generated by multiple descending pathways. Suppression of the early MEP is consistent with transmission along the fast-conducting corticospinal tract, whereas facilitation of the late MEP suggests transmission along a corticofugal, potentially cortico-reticulospinal, pathway. Accordingly, differences in late MEP modulation between the first dorsal interosseous and gastrocnemius reflect an increased role of corticofugal pathways in the control of postural muscles.

Activity-related pain and sensitization predict within- and between-person pain experience in people with knee osteoarthritis: An ecological momentary assessment study.

Background and objectives: Knee Osteoarthritis (OA) is a prevalent musculoskeletal condition that often results in pain and disability. Determining factors predicting variability in pain experience is critical to improving clinical outcomes. Underlying pain sensitization and its clinical manifestations, such as activity-related pain, may better predict the knee OA pain experience. This study aimed to determine whether Quantitative Sensory Testing (QST) derived sensitization measures and activity-related pain predict knee OA pain experiences collected via smartphone ecological momentary assessment (EMA). Design: Individuals with knee OA were recruited from an urban community in New Zealand. Those eligible to participate underwent baseline QST with clinical measures of activity-related pain also being collected. The knee OA pain experience was collected via smartphone EMA three times daily for two weeks. Mixed effects location scale models were developed using a multilevel modelling approach. Results: Eighty-six participants with knee OA participated in the study. Mean age was 67.3 years, with most of the participants being female (64%) and New Zealand European (90.6%). Activity-related pain predicted worse and more variable pain intensity, pain interference, and bothersomeness outcomes within and between individuals with knee OA. Widespread cold hyperalgesia and local mechanical hyperalgesia were shown to predict higher within-person variability in pain intensity and pain interference respectively, while mechanical temporal summation predicted less within-person variability in pain intensity and interference. Discussion: Those demonstrating activity-related pain and sensitization could be at risk of experiencing worse and more variable knee OA pain in the subsequent weeks. Testing for sensitization in clinical practice could therefore identify those at greatest risk of higher and more variable knee OA pain experiences and in greatest need of treatment. Larger validation studies are required, which include individuals with more severe knee OA.

Experiences and Perceptions of Using Smartphone Ecological Momentary Assessment for Reporting Knee Osteoarthritis Pain and Symptoms.

BACKGROUND: Knee osteoarthritis (OA) is a prevalent, painful, and disabling musculoskeletal condition. One method that could more accurately monitor the pain associated with knee OA is ecological momentary assessment (EMA) using a smartphone. OBJECTIVES: The aim of this study was to explore participant experiences and perceptions of using smartphone EMA as a way of communicating knee OA pain and symptoms following participating in a 2-week smartphone EMA study. MATERIALS AND METHODS: Using a maximum variation sampling method, participants were invited to share their thoughts and opinions in semistructured focus group interviews. Interviews were recorded and transcribed verbatim before thematic analysis using the general inductive approach. RESULTS: A total of 20 participants participated in 6 focus groups. Three themes and 7 subthemes were identified from the data. Identified themes included: user experience of smartphone EMA, data quality of smartphone EMA, and practical aspects of smartphone EMA. DISCUSSION: Overall, smartphone EMA was deemed as being an acceptable method for monitoring pain and symptoms associated with knee OA. These findings will assist researchers in designing future EMA studies alongside clinicians implementing smartphone EMA into practice. PERSPECTIVE: This study highlights that smartphone EMA is an acceptable method for capturing pain-related symptoms and experiences of those expereiencing knee OA. Future EMA studies should ensure design features are considered that reduce missing data and limit the responder burden to improve data quality.

Are Ecological Momentary Assessments of Pain Valid and Reliable? A Systematic Review and Meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to determine the level of evidence for the psychometric properties of Ecological Momentary Assessment (EMA) in populations with persistent pain. MATERIALS AND METHODS: Five databases were searched from 1980 to December 2021. Two reviewers independently screened the titles, abstracts, and full text, extracted data, and assessed adherence to reporting standards and methodological rigor before evaluating the quality of evidence. A meta-analysis, including the pooling of correlations for the relevant EMA pain outcomes, was completed. RESULTS: Overall, 3270 studies were identified, with 14 studies meeting inclusion criteria. Meta-analyses confirmed good to excellent relationships demonstrated between EMA and recalled pain intensity and interference across different timeframes. Many of the included studies did not fully adhere to recommended reporting standards, and the quality of included studies was either doubtful or inadequate due to methodological flaws. The level of evidence for measurement properties of pain outcomes was low for the criterion validity of pain intensity and interference and very low for reliability and construct validity of pain intensity and interference. DISCUSSION: Ecological momentary assessment of pain experience appears both valid and reliable. Although the levels of evidence were low or very low, these findings provide preliminary support for the use of EMA in clinical practice and research settings. Potential strengths of EMA include providing measures with greater ecological validity while also reducing recall bias, both pertinent in pain outcome measurement. More research, including higher-quality studies, is needed to demonstrate further support for EMA, including the need for establishing other types of validity.

Somatosensory assessments in patients with inflammatory bowel disease: a cross-sectional study examining pain processing pathways and the role of multiple patient factors.

BACKGROUND: Pain affects the majority of patients with inflammatory bowel disease (IBD), where pain experiences may be influenced by multiple patient factors and changes within central pain processing pathways, termed central sensitization. The current study aimed to investigate pain processing pathways in patients with IBD through somatosensory testing and associations with multiple patient factors. METHODS: A cross-sectional study of adults with IBD. Assessments included: somatosensory tests [i.e. pressure pain thresholds (PPT), temporal summation (TS), conditioned pain modulation (CPM)], and patient factors (i.e. demographics, comorbidity, sleep quality, psychological, pain severity and interference, and IBD features). Multiple regression analyses explored associations between somatosensory tests and multiple patient factors. RESULTS: Decreased CPM in participants (N = 51) was associated with worse abdominal pain severity and use of biologic therapies (R2 = 0.30, F(5,44) = 5.18, P = 0.001). Increased TS was associated with biologic use (R2 = 0.11, F(1,49) = 6.13, P = 0.017). Decreased PPT at the low back (R2 = 0.29, F(2,48) = 11.21, P < 0.001) and Tibialis anterior (R2 = 0.41, F(2,48) = 18.26, P < 0.001) were associated with female sex and the absence of a stoma. CONCLUSION: Study results demonstrated associations between multiple patient factors and somatosensory tests in patients with IBD. The absence of a stoma and female sex was associated with greater sensitivity to pressure in two remote body regions, suggestive of widespread hyperalgesia. Worse abdominal pain severity and biologic use were associated with decreased pain inhibition, and biologic use was also associated with increased pain facilitation. These findings suggest the presence of altered pain processing and mechanisms of central sensitization in patients with IBD.

Inflammatory Bowel Disease and Pain Interference: A Conceptual Model for the Role of Insomnia, Fatigue, and Pain Catastrophizing.

Background: People with inflammatory bowel disease (IBD) commonly experience pain influenced by complex interactions among factors, including disease activity, sleep, psychopathology, and changes in pain processing pathways. Treatments for pain in IBD are limited, highlighting the need for research that explores modifiable factors linked to pain. The aim of this study was to investigate relationships among multiple patient factors and to construct a conceptual model for pain interference in IBD. Methods: A cross-sectional survey of adults with IBD. Study domains included demographic, comorbidity, psychological, IBD, insomnia, fatigue, and pain features. Structural equation modeling (SEM) was used to examine relationships and interactions among active IBD, insomnia, fatigue, pain experiences (severity, catastrophizing, and interference), and additional patient factors (demographics and psychological). Results: One hundred and seventy-four participants, aged 18-85 years, reported the presence of pain. Combining the questionnaire data using SEM resulted in a final model with an excellent fit (χ 2(8) = 9.579, P = .297, χ 2/N = 1.197, CFIN = 0.997, TLI = 0.987, RMSEA = 0.034). The presence of anxiety and depression was the additional patient factors to be retained in the path analysis. SEM results indicated that greater pain interference was directly influenced by greater fatigue, worse pain catastrophizing, and worse pain severity. Pain interference was indirectly impacted by IBD activity, worse insomnia, and the presence of depression and anxiety. Conclusions: The proposed conceptual model highlights the role of multiple potentially modifiable factors, including insomnia, pain catastrophizing, and fatigue, contributing to worse pain interference in people with IBD.

Activity-related pain predicts pain and functional outcomes in people with knee osteoarthritis: A longitudinal study.

Knee Osteoarthritis (OA) is a prevalent musculoskeletal condition, commonly resulting in pain and disability. However, pain and disability in this population are poorly related with the degree of structural joint damage. Underlying pain mechanisms, including activity-related pain and sensitization assessed via Quantitative Sensory Testing (QST), may better predict pain and functional outcomes of those with knee OA. Therefore, the aim of this study was to explore whether activity-related pain and sensitization assessed via QST predict future pain, function, fatigue, physical performance and quality of life outcomes in those living in the community with knee OA. Eighty-six participants with knee OA were recruited in Dunedin, New Zealand. Those eligible to participate underwent baseline testing including QST as well as measures of activity-related pain including Movement-evoked Pain (MEP) and Sensitivity to Physical Activity (SPA). Outcome measures exploring pain, function, fatigue and quality of life outcomes were collected at baseline, and two follow-up periods (two and nine weeks). Univariable linear regression models were developed followed by multivariable linear regression models for each prognostic marker adjusting for age, gender, BMI, OA duration, baseline pain intensity and socioeconomic status. Activity-related measures of pain, including MEP and SPA, demonstrated predictive associations with pain and functional outcomes prospectively in those with knee OA. Therefore, those demonstrating activity-related pain are at future risk of greater pain, disability and reduced quality of life. Larger, externally validated longitudinal studies are required which include individuals with more severe knee OA.

Symptoms of central sensitization in patients with inflammatory bowel diseases: a case-control study examining the role of musculoskeletal pain and psychological factors.

OBJECTIVES: Musculoskeletal (MSK) pain is a common complaint in patients with inflammatory bowel diseases (IBD). MSK pain in IBD has previously demonstrated association with symptoms of central sensitization; however it is uncertain whether these symptoms are influenced simply by the presence of MSK pain and/or IBD. Primary aim of this study was to investigate whether symptoms of central sensitization differed across three groups: IBD patients with and without MSK pain and healthy controls. Secondary aim was to investigate between-group differences for measures of somatosensory functioning. METHODS: Cross-sectional study was performed on adults with IBD. Assessments included: central sensitization inventory (CSI), pressure pain threshold, temporal summation, conditioned pain modulation, perceived stress, affect style, anxiety, depression, and pain catastrophizing. One-way analyses of variance and covariance were used to investigate between-group differences for measures of central sensitization and potential confounding by psychological factors. RESULTS: Study participants (n=66) were age/gender matched across three study groups. Between-group differences were solely demonstrated for CSI scores [F(2,63)=19.835, p<0.001, r=0.62], with IBD patients with MSK pain demonstrating the highest CSI scores and healthy controls the lowest. After controlling for individual psychological features, post hoc comparisons indicated that CSI scores were significantly different between-groups (p≤0.025) after controlling for most psychological variables, with the exception of perceived stress (p=0.063) and pain catastrophizing (p=0.593). CONCLUSIONS: IBD patients as a whole demonstrated significantly greater symptoms of central sensitization compared to healthy controls. However, IBD patients with persistent MSK pain demonstrated the greatest symptoms of central sensitization compared to patients without MSK pain and healthy controls. Between-group differences for CSI in IBD patients with MSK were not confounded by psychological features. IMPLICATIONS: Study results indicate that persistent MSK pain in IBD represents patients with greater central sensitization symptomology. This increased symptomology is suggestive of underlying mechanisms related to central sensitization, highlighting patient potentially at risk for worse pain experiences.

Criterion validity and discriminatory ability of the central sensitization inventory short form in individuals with inflammatory bowel diseases.

OBJECTIVES: Increased symptoms related to central sensitization have previously been reported in inflammatory bowel disease (IBD) patients, identified by the original central sensitization inventory (CSI-25). However, the recently developed CSI short form (CSI-9) may be more clinically useful. The aim of the present study was to evaluate the performance of CSI-9 compared to the original CSI-25 in individuals with IBD. Study objectives were to investigate the criterion validity of the CSI-9 to the CSI-25, assess individual association of the CSI measures with clinical features of IBD and pain presentations, and to establish disease-specific CSI-9 and CSI-25 cut-off scores for discriminating the presence of self-reported pain in individuals with IBD. METHODS: Cross-sectional online survey was performed on adults with IBD exploring self-reported demographics, comorbidity, and clinical IBD and pain features. Criterion validity of the CSI-9 was investigated using intraclass correlation coefficient (ICC)3,1. Area under the receiver operating characteristic curve (AUC-ROC) analysis was conducted to investigate the discriminative ability of both versions of CSI. RESULTS: Of the 320 participants, 260 reported the presence of abdominal and/or musculoskeletal pain. CSI-9 and CSI-25 demonstrated substantial agreement (ICC3,1=0.64, 95% CI [0.58, 0.69]). AUC (95% CI) indicated that CSI-9 (0.788 (0.725, 0.851), p<0.001) and CSI-25 (0.808 (0.750, 0.867), p<0.001) were able to adequately discriminate the presence of pain using cut-offs scores of ≥17 (CSI-9) and ≥40 (CSI-25). Abdominal pain severity was the only feature to differ in significant association to CSI-25 (p=0.002) compared to CSI-9 (p=0.236). All other features demonstrated significant associations to both CSI versions, except age (p=0.291 and 0.643) and IBD subtype (p=0.115 and 0.675). CONCLUSIONS: This is the first study to explore and validate the use of CSI-9 in IBD patients. Results demonstrated concurrent validity of the CSI-9 to CSI-25, with similar significant association to multiple patient features, and a suggested cut-off value of 17 on CSI-9 to screen for individuals with pain experiences. Study findings suggest that CSI-9 is suitable to use as a brief tool in IBD patients.

Central Sensitization Inventory Mediates the Relationship Between Inflammatory Bowel Disease Activity and Worse Musculoskeletal Pain Experiences.

BACKGROUND: Musculoskeletal conditions are well documented in inflammatory bowel disease (IBD). However, whether IBD activity influences musculoskeletal pain experiences is uncertain. Central sensitization has been proposed in patients with IBD who are suffering from persistent pain. Identification of central sensitization symptomology using the Central Sensitization Inventory (CSI) has been reported in many pain-related disorders. Aims of this study were to explore predictive relationships between IBD activity and musculoskeletal pain experiences (severity/interference), and the mediating effects of the CSI. METHODS: A cross-sectional online survey was performed exploring self-reported musculoskeletal pain in adults with IBD. Survey questionnaires included IBD activity indices, numeric rating scales, PROMIS Pain Interference, and the CSI. Linear regression was used to examine the relationship between active IBD and pain experiences. Simple and serial mediation analyses were used to explore mediation models: independent variable (IBD activity), dependent variables (severity/interference), and mediators (CSI/severity). RESULTS: 208 adults with IBD, 18 to 88 years of age, reported musculoskeletal pain. Regression analysis identified IBD activity as a significant predictor of worse pain severity (R2  = 0.039, P < 0.005) and interference (R2  = 0.067, P < 0.001). Simple mediation showed a significant indirect effect from CSI scores between IBD activity and pain severity. Serial mediation analysis showed a significant indirect effect from CSI scores and pain severity, between IBD activity and pain interference. CONCLUSION: Active IBD demonstrated a positive association with worse musculoskeletal pain experiences. The CSI demonstrated significant mediation between active IBD and pain severity. Additionally, the CSI and pain severity demonstrated significant mediation between active IBD and pain interference. This suggests that symptoms of central sensitization significantly influence musculoskeletal pain experiences in IBD.

Central hypersensitivity - A model for persistent musculoskeletal pain in inflammatory bowel diseases.

Pain is reported to affect over 70% of individuals with inflammatory bowel diseases (IBD), with abdominal and musculoskeletal (MSK) pain representing the most common complaints. MSK pain is typically considered within the narrow framework of inflammatory extraintestinal manifestations of IBD, resulting in a limited scope for the nature and underlying mechanisms participating in MSK pain experiences in this population. Symptoms related to central sensitization have recently demonstrated association with active IBD and worse MSK pain experiences, suggesting a potential roll for central mechanisms in MSK-related pain. Current literature exploring persistent pain in chronic inflammatory and MSK populations propose complex pain models comprised of dynamic nervous system relationships influenced by primary disease features and concomitant pain states, as well as affective and cognitive components. Nervous system contributions in the development and maintenance of persistent pain are postulated to include mechanisms of peripheral and central sensitization, changes in descending central modulation, as well as structural brain changes. These models go beyond current MSK pain models described in IBD literature, highlighting the need for new frameworks for considering MSK-related pain in IBD. Consequently, this paper proposes a broader theoretical model whereby central mechanisms, such as central sensitization and grey matter changes, as well as psychological and disease factors are suggested to modulate pain experiences in this population. Exploration of relationships within the proposed framework may provide not only a deeper understanding of the generation and maintenance of persistent MSK pain in IBD, but also highlight the need for new targeted management pathways in this population. This paper hypothesizes that exploration of central sensitization in IBD patients will demonstrate altered somatosensory functioning in patients with MSK pain, and that IBD activity and psychological factors will be associated with altered somatosensory functioning and worse pain experiences.

Musculoskeletal Pain in Individuals With Inflammatory Bowel Disease Reflects Three Distinct Profiles.

OBJECTIVES: Pain affects over 70% of individuals with inflammatory bowel disease (IBD), with abdominal and musculoskeletal pain representing the most common symptoms. Musculoskeletal pain in IBD is reported to be associated with multiple clinical features, however the scope and nature of pain is not well understood. Primary aims were to identify subgroups of musculoskeletal pain in individuals with IBD based on clinical features of pain and assess how these subgroups differ in aspects of demographics, comorbidity, and IBD characteristics. METHODS: Cross-sectional online survey was performed on adults with IBD. Domains included: demographics, comorbidity, and clinical IBD and pain features. Latent class analysis was used to identify subgroups with similar attributes of: pain (severity, location, interference, and quality), IBD (activity, quality of life, and abdominal pain), and symptoms related to central sensitization. Correlation and regression analyses were used to profile identified subgroups. RESULTS: Of 305 included participants, 208 indicated the presence of musculoskeletal pain. Three identified subgroups were characterized as "mixed mechanism," "central mechanism," and "regional and remission." Between subgroup differences included: total comorbidity score (P=0.005), osteoarthritis (P=0.027), osteoporosis (P=0.045), depression (P=0.001), anxiety (P=0.025), and chronic fatigue syndrome (P=0.020). Sex and age were identified as confounders for depression and anxiety. CONCLUSIONS: Study results suggest multiple mechanisms contributing to pain experiences in IBD, to include central mechanisms. Features related to demographics, extraintestinal manifestations, IBD subtype, and clinical IBD features were not predictors of subgroup membership. However, total comorbidity demonstrated association with pain subgroups in this population.

Shoulder muscle activity during the modified dynamic relocation test and side-lying shoulder external rotation: a cross-sectional study on asymptomatic individuals.

OBJECTIVES: (1) to compare activity levels between monitored muscles during the dynamic relocation test (DRT); (2) to assess changes in muscle activation variability over 10 trials; (3) to assess within-muscle difference activity levels between the DRT and the unloaded side-lying shoulder external rotation exercise. METHODS: This is a cross-sectional, laboratory-based, repeated measures study. Thirty asymptomatic individuals performed the DRT and unloaded side-lying external rotation. The order of exercises was randomized. Superficial electromyography was used for recording the supraspinatus, infraspinatus, middle deltoid, posterior deltoid, pectoralis major, and latissimus dorsi muscles. The main outcome measures were mean muscle activity, expressed as % of maximal isometric voluntary contraction. RESULTS: We found significant between-muscles differences in activity (Ft = 14.11, p < 0.001) during the DRT. Post hoc analysis suggested between-trial variability did not change over the 10 trials, (F = 18.2, p < 0.001). Within-muscle comparisons between the DRT and side-lying shoulder external rotation suggested significant differences between these exercises (F = 32.37, p < 0.001). CONCLUSIONS: considering the monitored muscles, supraspinatus, infraspinatus, pectoralis major, and latissimus dorsi are the main muscles contracting during the DRT. Of all monitored muscles, supraspinatus muscle was the only one presenting higher activity levels during the DRT when compared to the unloaded side-lying shoulder external rotation.

Regional asymmetry, obesity and gender determines tactile acuity of the knee regions: A cross-sectional study.

BACKGROUND AND AIMS: Alterations in central somatosensory function (e.g. cortical reorganisation) occurs secondary to chronic knee pain. The reorganization can be quantified using a clinical signatory measure, the two-point discrimination threshold (TPDT). In order to differentiate normal variability of TPDT against abnormal thresholds for clinical practice, development of body region specific reference values are required and the factors that determine the TPDT have to be established. OBJECTIVE: To establish reference values for TPDT of the knee region in healthy individuals and to determine the factors that influence the TPDT of the knee regions. METHODS: Participants across four decades (18-59 years; n = 79) were recruited. TPDT estimates for medial and lateral knee regions were determined using a mechanical calliper. Descriptive statistics, and linear regression analyses were performed to establish reference TPDT values, and to investigate associations between demographics, anthropometric variables, and TPDT estimates respectively. RESULTS: Participants' Mean (SD) age = 38.3 (12.2); females (n = 56); and right lower limb dominant (n = 72). Mean TPDT threshold ranges included: lateral right knee, 36.7 (14.3); medial right knee, 28.6 (9.7); lateral left knee, 37.7 (12.9); and medial left knee, 27.9 (11.4). Fifteen percent of the threshold variance (R2 = 0.148) of TPDT estimates was explained by the medial aspect (ß = -8.9; p = 0.000) and male gender (ß = 3.1; p = 0.057), weighted by anthropometric factors. CONCLUSIONS: Age-stratified knee TPDT estimates have been reported to aid clinical interpretation. Regional asymmetry, gender, and obesity indices are factors that determine the TPDT of the knee. Normal TPDT asymmetry observed at medial aspect of the knee has significantly greater acuity compared to the lateral knee.

Ageing and obesity indices influences the tactile acuity of the low back regions: A cross-sectional study.

BACKGROUND AND AIMS: Two-point discrimination threshold (TPDT) is increased in individuals with chronic low back pain. TPDT reference values and their determinants are required for clinical applications. Therefore, the aims of this research are to establish reference values for TPDT of the low back regions in healthy individuals, stratified for age, and to investigate the associations of demographic and anthropomorphic variables with TPDT. METHODS: Healthy individuals (n = 79) across four decades (Group-I:18-29; Group-II:30-39; Group-III:40-49; and Group-IV:50-59years) were recruited. A mechanical calliper tool was used to determine the low back TPDT (mm) using an adaptive staircase method. Descriptive statistics were calculated for TPDT for each age group. Paired t-tests (p ≤ 0.05) were used to assess within group differences in TPDT between body sides. Univariate and weighted least squared linear regression analyses were performed to investigate associations between TPDT estimates and demographics, and body mass index (BMI), waist hip ratio (WHR). RESULTS: Mean (SD) age = 38.3(12.2); 55 female; and 73 right lower limb dominant. Mean (SD) TPDT threshold for all age groups: right = 67.3(15.6), and left = 65.7(15.4). No significant differences between left and right sides of the low back except in group-IV (mean difference:5.6[0.7-10.5]; P = 0.028). A total of 18% of TPDT variance (adjusted R(2) = 0.183; ß = 0.6; p = ≤0.001) of low back regions was explained by age with BMI and WHR weighted independently. CONCLUSIONS: Age, BMI, and WHR were independently associated with TPDT of the low back, and the influence of age was significantly influenced by obesity indices.