A clinical assessment tool to improve the use of pain relief treatments in knee osteoarthritis

Background: In the UK, approximately 25% of individuals aged over 55 have chronic knee pain, often due to osteoarthritis (OA). Knee pain originates from the joint due to structural changes or inflammation (peripheral mechanisms), and is often intensified by processing of afferent signals by the central nervous system (central mechanisms). Imaging and psychophysical approaches could inform the presence of underlying mechanisms within individuals with knee pain but lack feasibility within clinical settings. Feasible and validated self-report approaches that can aid identification of knee OA pain mechanisms are currently unavailable. Objectives: [1] to generate a shortlist of self-report items which reflect traits associated with underlying pain mechanisms; [2] to select a valid set of self-report items that measure a phenotypic trait associated with pain mechanisms; [3] to investigate the ability of the newly identified items to predict 1-year pain outcomes; [4] to understand participants’ interpretation of items included within the developing questionnaire to inform item revision where necessary; [5] to evaluate the psychometric properties of a newly developed mechanism-based questionnaire. Methods: Item generation and selection was based on exploratory analysis of responses to shortlisted items by individuals reporting knee pain (n=2152) included within the ‘Knee Pain in the Community (KPIC)’ cohort study. A subset of these participants (knee pain n=322, no knee pain n=98) undertook Pressure Pain Detection Thresholds (PPT) assessments at baseline. Items measuring specific traits related to pain mechanisms were selected from the survey based on expert consensus, face validity, item association with underlying phenotypes measured by originating host questionnaires, adequate targeting, and PPT correlations. An underlying trait was sought by factor analysis of the selected items. To examine the predictive validity of baseline scores for the identified trait, logistic and linear regression models assessed associations with 1-year follow-up pain outcomes. Receiver-operator-characteristic (ROC) curves and areas-under-the-curve (AUC) compared the predictive strength of the identified trait to other predictors of pain outcome. Selected items were rewritten and included within the Central Aspects of Pain in the Knee (CAP-Knee) questionnaire. Cognitive interviews across individuals with knee pain (n=22) participating within the ’CAP-Knee study’ assessed participant interpretation of CAP-Knee items. Thematic analysis of participants’ discussions for each item was used to identify emergent themes which were categorised according to whether or not they were aligned to the intended interpretation of the item. Content analysis across interview transcripts allowed coding of participant responses following Tourangeau’s question response model: comprehension (completely-, partially or not completely aligned), retrieval (no-, partial- and complete- retrieval difficulty), judgement (certain initial or uncertain initial judgement) and response formulation (consistent or inconsistent). Items were rewritten and retested in another group of interviews if (i) a mixture of aligned and not aligned themes emerged from discussions for an item, and ii) >15% of participants provided responses related to codes of poor item function, including complete non-alignment, complete retrieval difficulty, uncertain initial response and no response consistency. Psychometric properties of the CAP-Knee were assessed in 250 community-based individuals with knee pain, of whom 76 completed the CAP-Knee twice over one month to measure repeatability. Results: Item generation and selection: Eight self-report items measuring traits of anxiety, depression, catastrophizing, neuropathic-like pain, fatigue, sleep disturbance, pain distribution, and cognitive impact were identified as likely indices of central pain mechanisms. PPTs were associated with items representing each trait and with their originating questionnaires. A single factor, interpreted as “central mechanisms trait” was identified across the 8 selected items and explained variation in PPT (R2 = 0.17) better than did any originating questionnaire (R2 = 0.10-0.13). Predictive Validity: The central mechanisms trait score significantly predicted year 1 pain outcomes, even after adjustment for age, sex, BMI, radiographic OA severity and symptom duration (Pain persistence: RR=2.14, n=204, p=0.001; Persistent pain severity: β=0.47, n=118; p<0.002). The central mechanisms trait score showed good discrimination power in distinguishing pain persistence cases from resolved pain cases (AUC = 0.70; n=1471). The discrimination power of other predictors, including radiographic OA (AUC = 0.62; n=204), age, sex and BMI (AUC range = 0.51 to 0.64; n=1471), improved significantly (p<0.04) when the central mechanisms trait was included in each logistic regression model (AUC range = 0.69 to 0.74). Interpretation of CAP-Knee items: Participant interpretation of the final version of the CAP-Knee items was closely aligned to their intended meaning. Overall, 15 key themes were discussed by participants for items included within the CAP-Knee {One Anxiety theme = Fear; two Depression themes = Social function, Physical limitation; two Catastrophizing themes = Causes and consequences, Avoidance behaviours; two Cognitive impact themes = Task distraction, and Hypervigilance; two Sleep themes = Sleep disturbance and Use of sleeping aids; two Fatigue themes = Source of fatigue, Fatigue relief; one Pain distribution theme = Painful sites and three Neuropathic-like pain themes = Thermal allodynia, Weather induced pain and Thermotherapy. A mixture of aligned and not aligned themes emerged from discussions about the Neuropathic-like pain- and depression- items. More than 15% of participants provided responses indicative of poor item performance for the Neuropathic-like pain item only, but not the depression item. The rewritten version of the neuropathic-like pain item was considered to work well. Psychometric properties of the CAP-Knee: CAP-Knee displayed a wide range of scores across the study population (median 8, range 0-24). Internal consistency was acceptable (α = 0.75) and test–retest reproducibility excellent (ICC=0.91, 95% CI, 0.86-0.94). All CAP-Knee items contributed significantly (item loading range = 0.21-0.92; p<0.01) to one distinct factor (CFI = 0.99; TLI= 0.98; X2(df)=37(20); RMSEA= 0.06). The CAP-Knee targeted the knee pain population well and constituted a unidimensional measure. Fit to the Rasch model was improved by item rescoring. Conclusion: The CAP-Knee is a simple and valid self-report questionnaire, consisting of the 8 selected items which measure a single latent trait (‘central mechanisms’) in individuals with knee pain, and may help identify and target treatments that aim to reduce central sensitisation. No items associated with peripheral mechanisms of knee OA pain were identified in this project. Future research should seek to clinically validate the stratification and prognostic characteristics of the CAP-Knee

An observational study of centrally facilitated pain in individuals with chronic low back pain

Central pain facilitation can hinder recovery in people with chronic low back pain (CLBP). The aim of this observational study was to investigate whether indices of centrally facilitated pain are associated with pain outcomes in a hospital-based cohort of individuals with CLBP undertaking a pain management programme. Participants provided self-report and pain sensitivity data at baseline (n=97), and again 3-months (n=87) after a cognitive behavioural therapy-based group intervention including physiotherapy. Indices of centrally facilitated pain were; Pressure Pain detection Threshold (PPT), Temporal Summation (TS) and Conditioned Pain Modulation (CPM) at the forearm, Widespread Pain Index (WPI) classified using a body manikin, and a Central Mechanisms Trait (CMT) factor derived from 8 self-reported characteristics of anxiety, depression, neuropathic pain, fatigue, cognitive dysfunction, pain distribution, catastrophizing and sleep. Pain severity was a composite factor derived from Numerical Rating Scales. Cross-sectional and longitudinal regression models were adjusted for age and sex. Baseline CMT and WPI each was associated with higher pain severity (CMT: r=0.50, p<0.001, WPI: r=0.21, p=0.04) at baseline as well as at 3 months (CMT: r=0.38, p<0.001, WPI: r=0.24, p=0.02). High baseline CMT remained significantly associated with pain at 3 months after additional adjustment for baseline pain (β=2.45, p=0.04, R2=0.25, p<0.0001). QST indices of pain hypersensitivity were not significantly associated with pain outcomes at baseline or at 3 months. In conclusion, central mechanisms beyond those captured by QST are associated with poor CLBP outcome and might be targets for improved therapy

Quantitative sensory testing and predicting outcomes for musculoskeletal pain, disability, and negative affect: a systematic review and meta-analysis

Hypersensitivity due to central pain mechanisms can influence recovery and lead to worse clinical outcomes, but the ability of quantitative sensory testing (QST), an index of sensitisation, to predict outcomes in chronic musculoskeletal disorders remains unclear. We systematically reviewed the evidence for ability of QST to predict pain, disability and negative affect using searches of CENTRAL, MEDLINE, EMBASE, AMED, CINAHL and PubMed databases up to April 2018. Title screening, data extraction, and methodological quality assessments were performed independently by 2 reviewers. Associations were reported between baseline QST and outcomes using adjusted (β) and unadjusted (r) correlations. Of the 37 eligible studies (n=3860 participants), 32 were prospective cohort studies and 5 randomised controlled trials. Pain was an outcome in 30 studies, disability in 11 and negative affect in 3. Metaanalysis revealed that baseline QST predicted musculoskeletal pain (mean r=0.31, 95%CI: 0.23 to 0.38, n=1057 participants) and disability (mean r=0.30, 95%CI: 0.19 to 0.40, n=290 participants). Baseline modalities quantifying central mechanisms such as temporal summation (TS) and conditioned pain modulation (CPM) were associated with follow-up pain (TS: mean r=0.37, 95%CI: 0.17 to 0.54; CPM: r=0.36, 95%CI: 0.20 to 0.50), whereas baseline mechanical threshold modalities were predictive of followup disability (mean r=0.25, 95%CI: 0.03 to 0.45). QST indices of pain hypersensitivity might help develop targeted interventions aiming to improve outcomes across a range of musculoskeletal conditions

The Central Aspects of Pain in the Knee (CAP-Knee) questionnaire; a mixed-methods study of a self-report instrument for assessing central mechanisms in people with knee pain

OBJECTIVES: Pain is the prevailing symptom of knee osteoarthritis. Central sensitisation creates discordance between pain and joint pathology. We previously reported a central pain mechanisms trait derived from 8 discrete characteristics: neuropathic-like pain, fatigue, cognitive-impact, catastrophising, anxiety, sleep disturbance, depression, and pain distribution. We here validate and show that an 8-item questionnaire, Central Aspects of Pain in the Knee (CAP-Knee) is associated both with sensory and affective components of knee pain severity.METHODS: Participants with knee pain were recruited from the Investigating Musculoskeletal Health and Wellbeing study in the East Midlands, UK. CAP-Knee items were refined following cognitive interviews. Psychometric properties were assessed in 250 participants using Rasch-, and factor-analysis, and Cronbach’s alpha. Intra-class correlation coefficients tested repeatability. Associations between CAP-Knee and McGill Pain questionnaire pain severity scores using linear regression.RESULTS: CAP-Knee targeted the knee pain sample well. Cognitive interviews indicated that participants interpreted CAP-Knee items in diverse ways aligned to their intended meanings. Fit to the Rasch model was optimised by rescoring each item, producing a summated score from 0-16. Internal consistency was acceptable (Cronbach’s alpha=0.74) and test–retest reliability excellent (ICC2,1=0.91). Each CAP-Knee item contributed uniquely to one discrete `Central Mechanisms trait’ factor. High CAP-Knee scores were associated with worse overall knee pain intensity and with each of sensory and affective McGill Pain Questionnaire scores.CONCLUSION: CAP-Knee is a simple and valid self-report questionnaire, which measures a single `Central Mechanisms’ trait, and may help identify and target centrally-acting treatments aiming to reduce the burden of knee pain

Traits associated with central pain augmentation in the Knee Pain in the Community (KPIC) cohort

This study aimed to identify self-report correlates of central pain augmentation in individuals with knee pain. A subset of participants (n=420) in the Knee Pain and related health In the Community (KPIC) baseline survey undertook pressure pain threshold (PPT) assessments. Items measuring specific traits related to central pain mechanisms were selected from the survey based on expert consensus, face validity, item association to underlying constructs measured by originating host questionnaires, adequate targeting and PPT correlations. Pain distribution was reported on a body manikin. A `central pain mechanisms’ factor was sought by factor analysis. Associations of items, the derived factor and originating questionnaires with PPTs were compared. Eight self-report items measuring traits of anxiety, depression, catastrophizing, neuropathic- like pain, fatigue, sleep disturbance, pain distribution and cognitive impact, were identified as likely indices of central pain mechanisms. PPTs were associated with items representing each trait and with their originating scales. Pain distribution classified as “pain below the waist additional to knee pain” was more strongly associated with low PPT than were alternative classifications of pain distribution. A single factor, interpreted as “central pain mechanisms”, was identified across the 8 selected items and explained variation in PPT (R² = 0.17) better than did any originating scale (R² = 0.10 to 0.13). In conclusion, including representative items within a composite self-report tool might help identify people with centrally augmented knee pain

Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA): protocol for a prospective observational study

Background: Pain and fatigue are persistent problems in people with rheumatoid arthritis. Central sensitisation (CS) may contribute to pain and fatigue, even when treatment has controlled inflammatory disease. This study aims to validate a self-report 8-item questionnaire, the Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) questionnaire, developed to measure central pain mechanisms in RA, and to predict patient outcomes and response to treatment. A secondary objective is to explore mechanisms linking CS, pain and fatigue in people with RA. Methods/design: This is a prospective observational cohort study recruiting 250 adults with active RA in secondary care. The CAP-RA questionnaire, demographic data, medical history, and patient reported outcome measures (PROMs) of traits associated with central sensitization will be collected using validated questionnaires. Quantitative sensory testing modalities of pressure pain detection thresholds, temporal summation and conditioned pain modulation will be indices of central sensitization, and blood markers, swollen joints and ultrasound scans will be indices of inflammation. Primary data collection will be at baseline and 12 weeks. The test-retest reliability of CAP-RA questionnaire will be determined 1 week after the baseline visit. Pain and fatigue data will be collected weekly via text messages for 12 weeks. CAP-RA psychometric properties, and predictive validity for outcomes at 3 months will be evaluated. Discussion: This study will validate a simple self-report questionnaire against psychophysical indices of central sensitization and patient reported outcome measures of traits associated with CS in a population of individuals with active RA. The application of this instrument in the clinical environment could provide a mechanism-based stratification tool to facilitate the provision of targeted therapy to individuals with pain and fatigue in RA, alongside treatments that target joint inflammation. Trial registration: Clinicaltrials.gov NCT04515589. Date of registration 17 August 2020

How people with knee pain understand why their pain changes or remains the same over time: A qualitative study

ObjectivesGuidelines recommend knee osteoarthritis pain management based on biopsychosocial mechanisms. Treatment adherence and effectiveness may be affected if there is a mismatch between patient perspectives and treatment focus. We therefore examined patient perspectives on mechanisms of their knee pain, why it persisted or changed over the past year, whether their understanding had changed, and whether their understanding aligned with that of others with whom they interact.MethodsIndividuals with chronic knee pain (n ​= ​50) were purposively recruited from the Knee Pain and related health In the Community (KPIC) cohort to represent worsened, improved, or unchanged pain or anxiety between baseline and one year later. Framework analysis, a comparative form of thematic analysis, was used across transcripts of semi-structured telephone interviews.ResultsData were collapsed into themes of diagnosis, joint structure, ageing, physical activity, weight management, and treatment. Participants focused on biomechanical rather than psychological pain mechanisms. Some participants attributed pain improvement to increased and others to decreased physical activity. Participants reported no change in their understanding of their pain during the preceding year, but that their attitudes to pain, for example acceptance, had changed. Participants reported that they and others around them lacked understanding of their pain and why it did or did not change.ConclusionPeople report a predominantly biomechanical understanding of why their knee pain remains constant or changes over time. Clinicians should support patients to develop a biopsychosocial understanding of knee pain aligned to treatment across the range of biological, psychological, and social modalities

A clinical assessment tool to improve the use of pain relief treatments in knee osteoarthritis

Background: In the UK, approximately 25% of individuals aged over 55 have chronic knee pain, often due to osteoarthritis (OA). Knee pain originates from the joint due to structural changes or inflammation (peripheral mechanisms), and is often intensified by processing of afferent signals by the central nervous system (central mechanisms). Imaging and psychophysical approaches could inform the presence of underlying mechanisms within individuals with knee pain but lack feasibility within clinical settings. Feasible and validated self-report approaches that can aid identification of knee OA pain mechanisms are currently unavailable. Objectives: [1] to generate a shortlist of self-report items which reflect traits associated with underlying pain mechanisms; [2] to select a valid set of self-report items that measure a phenotypic trait associated with pain mechanisms; [3] to investigate the ability of the newly identified items to predict 1-year pain outcomes; [4] to understand participants’ interpretation of items included within the developing questionnaire to inform item revision where necessary; [5] to evaluate the psychometric properties of a newly developed mechanism-based questionnaire. Methods: Item generation and selection was based on exploratory analysis of responses to shortlisted items by individuals reporting knee pain (n=2152) included within the ‘Knee Pain in the Community (KPIC)’ cohort study. A subset of these participants (knee pain n=322, no knee pain n=98) undertook Pressure Pain Detection Thresholds (PPT) assessments at baseline. Items measuring specific traits related to pain mechanisms were selected from the survey based on expert consensus, face validity, item association with underlying phenotypes measured by originating host questionnaires, adequate targeting, and PPT correlations. An underlying trait was sought by factor analysis of the selected items. To examine the predictive validity of baseline scores for the identified trait, logistic and linear regression models assessed associations with 1-year follow-up pain outcomes. Receiver-operator-characteristic (ROC) curves and areas-under-the-curve (AUC) compared the predictive strength of the identified trait to other predictors of pain outcome. Selected items were rewritten and included within the Central Aspects of Pain in the Knee (CAP-Knee) questionnaire. Cognitive interviews across individuals with knee pain (n=22) participating within the ’CAP-Knee study’ assessed participant interpretation of CAP-Knee items. Thematic analysis of participants’ discussions for each item was used to identify emergent themes which were categorised according to whether or not they were aligned to the intended interpretation of the item. Content analysis across interview transcripts allowed coding of participant responses following Tourangeau’s question response model: comprehension (completely-, partially or not completely aligned), retrieval (no-, partial- and complete- retrieval difficulty), judgement (certain initial or uncertain initial judgement) and response formulation (consistent or inconsistent). Items were rewritten and retested in another group of interviews if (i) a mixture of aligned and not aligned themes emerged from discussions for an item, and ii) >15% of participants provided responses related to codes of poor item function, including complete non-alignment, complete retrieval difficulty, uncertain initial response and no response consistency. Psychometric properties of the CAP-Knee were assessed in 250 community-based individuals with knee pain, of whom 76 completed the CAP-Knee twice over one month to measure repeatability. Results: Item generation and selection: Eight self-report items measuring traits of anxiety, depression, catastrophizing, neuropathic-like pain, fatigue, sleep disturbance, pain distribution, and cognitive impact were identified as likely indices of central pain mechanisms. PPTs were associated with items representing each trait and with their originating questionnaires. A single factor, interpreted as “central mechanisms trait” was identified across the 8 selected items and explained variation in PPT (R2 = 0.17) better than did any originating questionnaire (R2 = 0.10-0.13). Predictive Validity: The central mechanisms trait score significantly predicted year 1 pain outcomes, even after adjustment for age, sex, BMI, radiographic OA severity and symptom duration (Pain persistence: RR=2.14, n=204, p=0.001; Persistent pain severity: β=0.47, n=118; p<0.002). The central mechanisms trait score showed good discrimination power in distinguishing pain persistence cases from resolved pain cases (AUC = 0.70; n=1471). The discrimination power of other predictors, including radiographic OA (AUC = 0.62; n=204), age, sex and BMI (AUC range = 0.51 to 0.64; n=1471), improved significantly (p<0.04) when the central mechanisms trait was included in each logistic regression model (AUC range = 0.69 to 0.74). Interpretation of CAP-Knee items: Participant interpretation of the final version of the CAP-Knee items was closely aligned to their intended meaning. Overall, 15 key themes were discussed by participants for items included within the CAP-Knee {One Anxiety theme = Fear; two Depression themes = Social function, Physical limitation; two Catastrophizing themes = Causes and consequences, Avoidance behaviours; two Cognitive impact themes = Task distraction, and Hypervigilance; two Sleep themes = Sleep disturbance and Use of sleeping aids; two Fatigue themes = Source of fatigue, Fatigue relief; one Pain distribution theme = Painful sites and three Neuropathic-like pain themes = Thermal allodynia, Weather induced pain and Thermotherapy. A mixture of aligned and not aligned themes emerged from discussions about the Neuropathic-like pain- and depression- items. More than 15% of participants provided responses indicative of poor item performance for the Neuropathic-like pain item only, but not the depression item. The rewritten version of the neuropathic-like pain item was considered to work well. Psychometric properties of the CAP-Knee: CAP-Knee displayed a wide range of scores across the study population (median 8, range 0-24). Internal consistency was acceptable (α = 0.75) and test–retest reproducibility excellent (ICC=0.91, 95% CI, 0.86-0.94). All CAP-Knee items contributed significantly (item loading range = 0.21-0.92; p<0.01) to one distinct factor (CFI = 0.99; TLI= 0.98; X2(df)=37(20); RMSEA= 0.06). The CAP-Knee targeted the knee pain population well and constituted a unidimensional measure. Fit to the Rasch model was improved by item rescoring. Conclusion: The CAP-Knee is a simple and valid self-report questionnaire, consisting of the 8 selected items which measure a single latent trait (‘central mechanisms’) in individuals with knee pain, and may help identify and target treatments that aim to reduce central sensitisation. No items associated with peripheral mechanisms of knee OA pain were identified in this project. Future research should seek to clinically validate the stratification and prognostic characteristics of the CAP-Knee

Women’s entrepreneurship, health-related crisis, and a gender-sensitive crisis management model for sustainable development

A crisis often impacts women’s entrepreneurship in ways different from their male counterparts. Thus, the purpose of this study is to introduce a crisis management model that can guide the formulation of policies to facilitate the sustainability of women’s entrepreneurial activities during a health-related crisis within developing economies. To do this, we utilised a case study research design that involved the in-depth interview of four women entrepreneurs who operated small businesses in Lagos, Nigeria. We utilised the findings to develop a gender-sensitive perspective to managing health crises. This is crucial as it offers stakeholders the foundation for building customised policies that can profoundly impact women-owned businesses. It also offers insights into strategies that can be put in place before and during a crisis to mitigate the adverse impacts of a crisis. This study advances a gender-sensitive perspective as a more practical approach to understand women’s entrepreneurial activities during a crisis

An incremental dual-task paradigm to investigate pain attenuation by task difficulty, affective content and threat value.

There is accumulating evidence that task demands and psychological states can affect perceived pain intensity. Different accounts have been proposed to explain this attenuation based either on how limited attentional resources are allocated to the pain stimulus or on how the threat value of the pain stimulus biases attention. However, the evidence for both proposals remains mixed. Here we introduce an incremental dual-task paradigm in which participants were asked to detect pain on their fingertip without any additional tasks during baseline phases or while concurrently detecting visual targets during task phases. The force applied to participants' fingertip in all phases increased incrementally until they detected moderate pain. In Experiment 1, we used coloured shapes and in Experiment 2 we used affective images as visual targets. We also manipulated the threat value of the pain stimulus in Experiment 2. For both experiments, we found that a concurrent task attenuated perceived pain intensity: mean force was significantly greater for the same moderate pain during task compared to baseline phases. Furthermore although task difficulty and affective content did not affect pain perception, the threat value of the pain stimulus moderated the magnitude of pain attenuation