Nervous System Sensitization as a Predictor of Outcome in the Treatment of Peripheral Musculoskeletal Conditions: A Systematic Review.

BACKGROUND: Research suggests that peripheral and central nervous system sensitization can contribute to the overall pain experience in peripheral musculoskeletal (MSK) conditions. It is unclear, however, whether sensitization of the nervous system results in poorer outcomes following the treatment. This systematic review investigated whether nervous system sensitization in peripheral MSK conditions predicts poorer clinical outcomes in response to a surgical or conservative intervention. METHODS: Four electronic databases were searched to identify the relevant studies. Eligible studies had a prospective design, with a follow-up assessing the outcome in terms of pain or disability. Studies that used baseline indices of nervous system sensitization were included, such as quantitative sensory testing (QST) or questionnaires that measured centrally mediated symptoms. RESULTS: Thirteen studies met the inclusion criteria, of which six were at a high risk of bias. The peripheral MSK conditions investigated were knee and hip osteoarthritis, shoulder pain, and elbow tendinopathy. QST parameters indicative of sensitization (lower electrical pain thresholds, cold hyperalgesia, enhanced temporal summation, lower punctate sharpness thresholds) were associated with negative outcome (more pain or disability) in 5 small exploratory studies. Larger studies that accounted for multiple confounders in design and analysis did not support a predictive relationship between QST parameters and outcome. Two studies used self-report measures to capture comorbid centrally mediated symptoms, and found higher questionnaire scores were independently predictive of more persistent pain following a total joint arthroplasty. CONCLUSION: This systematic review found insufficient evidence to support an independent predictive relationship between QST measures of nervous system sensitization and treatment outcome. Self-report measures demonstrated better predictive ability. Further high-quality prognostic research is warranted.

Intraexaminer and interexaminer reliability of manual palpation and pressure algometry of the lower limb nerves in asymptomatic subjects.

OBJECTIVE: Nerve palpation is a method of clinically identifying mechanosensitivity of neural tissue by means of pressure algometry and manual palpation. There are few investigations of the reliability of lower limb nerve palpation, and femoral nerve palpation has never been previously reported. The aim of this study was to investigate the reliability of nerve palpation of the femoral, sciatic, tibial, and common peroneal nerves and to report normative values for the femoral nerve. METHODS: The 4 lower limb nerves were palpated in 39 healthy volunteers using pressure algometry and manual digital palpation. Measurements were taken twice by 1 rater (intrarater reliability) and once by a second rater (interrater reliability). RESULTS: Intraclass correlation coefficients for pressure pain thresholds (PPTs) via pressure algometry of the femoral, common peroneal, tibial, and sciatic nerves were 0.69, 0.84, 0.64, and 0.9 for intrarater reliability, respectively, and 0.82, 0.7, 0.56, and 0.75 for interrater reliability. κ Values for manual palpation were 0.59, 0.55, 0.42, and 0.60 for intrarater reliability and 0.30, 0.49, 0.37, and 0.60 for interrater reliability. Males demonstrated significantly higher PPTs than females for the femoral, sciatic, and tibial nerves, and differences in PPTs were present between right and left sides. CONCLUSION: Nerve palpation of the femoral, common peroneal, and sciatic nerves using pressure algometry demonstrated good to excellent reliability, whereas the tibial nerve PPTs showed moderate to good reliability. Manual palpation measurements demonstrated fair to moderate reliability.

Acceptability of the combined online interactive mindfulness and exercise programme (MOVE-Online) for adults with chronic pain - A qualitative study.

PURPOSE: The aim of this qualitative study was to utilise the recent Theoretical Framework of Acceptability (TFA) to explore participants' acceptability of the mindfulness and exercise interventions in the MOVE-Online pain management programme (PMP) and the programmes' online delivery method. METHODS: Online focus groups were carried out following the completion of the PMP. The data were analysed using template analysis in terms of the seven TFA constructs of acceptability [(i) Perceived Effectiveness, (ii) Affective Attitude, (iii) Self-Efficacy, (iv) Ethicality, (v) Burden, (vi) Opportunity Costs and (vii) Intervention Coherence]. RESULTS: Twenty-one participants took part in the focus groups. Five of the seven TFA constructs of acceptability were identified in the analysis. The participants perceived the intervention to have been effective at achieving the goals of the PMP (TFA construct: (i) Perceived Effectiveness), to have supported their emotional management ((ii) Affective Attitude), promoted long term self-directed engagement ((iii) Self-Efficacy), fostered a valued group environment ((iv) Ethicality) and the online delivery of the programme reduced the physical burden associated with participation at an in-person PMP ((v) Burden). CONCLUSION: The results of the study supports the utility of the TFA as a tool to explore the multi-dimensional construct of acceptability for the participants in the MOVE-Online programme.

This investigation contributes to the understanding of acceptability as a complex multidimensional construct and emphasises the importance of considering the multiple dimensions when evaluating participants interpretations of novel complex interventions.Results suggest that participants found a pain management programme delivered in a live, online, interactive format to be acceptable, and it may be useful for rehabilitation professionals as an option for chronic pain management.

Combined online interactive mindfulness and exercise programme (MOVE-Online) compared with a self-management guide for adults with chronic pain: protocol for a randomised controlled feasibility trial.

INTRODUCTION: Online pain management programmes (PMP) have growing evidence as effective interventions for individuals with chronic pain (CP). Mindfulness-based stress reduction (MBSR) is a psychological intervention proven to be effective in the management of CP. There is also a large body of evidence for the efficacy of exercise in the management of CP however, there are limited studies combining both these interventions and none to date delivering a combined intervention in the form of an online PMP. This study aims to explore the acceptability and feasibility of delivering a combined MBSR and exercise online PMP for adults with CP, and will examine the feasibility of conducting a randomised controlled trial of a combined MBSR and exercise online programme compared with an online self-management guide. METHODS AND ANALYSIS: A parallel-group, feasibility randomised controlled trial (RCT) will be conducted among participants in Ireland, which will include an embedded qualitative study. Seventy-five participants will complete an online consent form and be individually randomised to one of two groups. Group A will participate in live online MBSR and supervised exercise sessions (2 hours MBSR, 1 hour exercise) once a week for 8 weeks. Group B will receive access to an 8-week online self-management guide, released biweekly and containing eight self-directed modules. Analyses of the feasibility study will be descriptive and will address the outcomes relating to the feasibility and acceptability of the interventions and procedures of the study including recruitment and eligibility, data collection methods, intervention adherence, engagement and attrition rates, intervention acceptability and participants' subjective perceptions of the programmes. Comparisons of clinical treatment effects, using validated patient-reported outcome measures will be explored descriptively to consider the viability of investigating a combined online MBSR and exercise intervention in a future fully powered RCT. ETHICS AND DISSEMINATION: This study was approved by the Mater Misericordiae University Hospital Institutional Review Board (1/378/2124) and the University College Dublin Human Research Ethics Committee (LS-20-76-Deegan-Doody). Informed consent will be obtained from each participant prior to randomisation. The results of this feasibility study will be published in peer-reviewed academic journals and presented at national and international conferences. TRIAL REGISTRATION: NCT04899622.

Multidimensional pain profiling in people living with obesity and attending weight management services: a protocol for a longitudinal cohort study.

INTRODUCTION: Pain is prevalent in people living with overweight and obesity. Obesity is associated with increased self-reported pain intensity and pain-related disability, reductions in physical functioning and poorer psychological well-being. People living with obesity tend to respond less well to pain treatments or management compared with people living without obesity. Mechanisms linking obesity and pain are complex and may include contributions from and interactions between physiological, behavioural, psychological, sociocultural, biomechanical and genetic factors. Our aim is to study the multidimensional pain profiles of people living with obesity, over time, in an attempt to better understand the relationship between obesity and pain. METHODS AND ANALYSIS: This longitudinal observational cohort study will recruit (n=216) people living with obesity and who are newly attending three weight management services in Ireland. Participants will complete questionnaires that assess their multidimensional biopsychosocial pain experience at baseline and at 3, 6, 12 and 18 months post-recruitment. Quantitative analyses will characterise the multidimensional pain experiences and trajectories of the cohort as a whole and in defined subgroups. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics and Medical Research Committee of St Vincent's Healthcare Group, Dublin, Ireland (reference no: RS21-059) and the University College Dublin Human Research Ethics Committee (reference no: LS-E-22-41-Hinwood-Smart). Findings will be disseminated through peer-reviewed journals, conference presentations, public and patient advocacy groups, and social media. STUDY REGISTRATION: Open Science Framework Registration DOI: https://doi.org/10.17605/OSF.IO/QCWUE.

Reliability of thermal quantitative sensory testing of the hand in a cohort of young, healthy adults.

INTRODUCTION: The reliability of thermal quantitative sensory testing (QST) has yet to be fully established. In this study we investigated intra- and interrater reliability of thermal QST in a blinded manner. METHODS: Two investigators recorded thermal detection and pain thresholds on the hand of 22 volunteers, twice on two occasions. Results were analyzed using descriptive statistics, intraclass correlation coefficients (ICCs), and coefficients of variation (CVs). RESULTS: Mean intraindividual differences were small for all measures except cold pain thresholds. ICC values for intra- and interrater reliability were: cold detection, 0.27-0.55; warm detection, 0.33-0.69; and heat pain, 0.39-0.86. Cold pain yielded high ICC values (0.87-0.94), but also high CV (84.9-90.2%). CONCLUSIONS: In young, healthy adults, thermal detection and heat pain thresholds of the hand demonstrated good reliability for group comparisons and individual analyses. Cold pain threshold measures may be suitable for group comparisons, but a large variance in the data limits individual analyses.

Pain sensitization associated with nonresponse after physiotherapy in people with knee osteoarthritis.

In knee osteoarthritis (OA), pain sensitization has been linked to a more severe symptomatology, but the prognostic implications of pain sensitivity in people undergoing conservative treatment such as physiotherapy are not established. This study aimed to prospectively investigate the association between features of pain sensitization and clinical outcome (nonresponse) after guideline-based physiotherapy in people with knee OA. Participants (n = 156) with moderate/severe knee OA were recruited from secondary care. All participants completed self-administered questionnaires and underwent quantitative sensory testing at baseline, thereby establishing subjective and objective measures of pain sensitization. Participants (n = 134) were later classified after a physiotherapy intervention, using treatment responder criteria (responder/nonresponder). Quantitative sensory testing data were reduced to a core set of latent variables using principal component analysis. A hierarchical logistic regression model was constructed to investigate whether features related to pain sensitization predicted nonresponse after controlling for other known predictors of poor outcome in knee OA. Higher temporal summation (odds ratio 2.00, 95% confidence interval 1.23-3.27) and lower pressure pain thresholds (odds ratio 0.48, 95% confidence interval 0.29-0.81) emerged as robust predictors of nonresponse after physiotherapy, along with a higher comorbidity score. The model demonstrated high sensitivity (87.8%) but modest specificity (52.3%). The independent relationship between pain sensitization and nonresponse may indicate an underlying explanatory association between neuroplastic changes in nociceptive processing and the maintenance of ongoing pain and disability in knee OA pain. These preliminary results suggest that interventions targeting pain sensitization may warrant future investigation in this population.

Exercise-induced Hypoalgesia in People With Knee Osteoarthritis With Normal and Abnormal Conditioned Pain Modulation.

OBJECTIVES: Normal efficiency of exercise-induced hypoalgesia (EIH) has been demonstrated in people with knee osteoarthritis (OA), while recent evidence suggests that EIH may be associated with features of pain sensitization such as abnormal conditioned pain modulation (CPM). The aim of this study was to investigate whether people with knee OA with abnormal CPM have dysfunctional EIH compared with those with normal CPM and pain-free controls. METHODS: Forty peoples with knee OA were subdivided into groups with abnormal and normal CPM, as determined by a decrease/increase in pressure pain thresholds (PPTs) following the cold pressor test. Abnormal CPM (n=19), normal CPM (n=21), and control participants (n=20) underwent PPT testing before, during, and after aerobic and isometric exercise protocols. Between-group differences were analyzed using repeated-measures analysis of variance and within-group differences were analyzed using Wilcoxon signed-rank tests. RESULTS: Significant differences were demonstrated between groups for changes in PPTs postaerobic (F2,55=4.860; P=0.011) and isometric (F2,57=4.727; P=0.013) exercise, with significant decreases in PPTs demonstrated during and postexercise in the abnormal CPM group (P<0.05), and significant increases in PPTs shown during and postexercise in the normal CPM and control groups (P<0.05). CONCLUSIONS: Results are suggestive of dysfunctional EIH in response to aerobic and isometric exercise in knee OA patients with abnormal CPM, and normal function of EIH in knee OA patients with an efficient CPM response. Identification of people with knee OA with inefficient endogenous pain modulation may allow for a more individualized and graded approach to exercises in these individuals.

The clinical utility of pain classification in non-specific arm pain.

Mechanisms-based pain classification has received considerable attention recently for its potential use in clinical decision making. A number of algorithms for pain classification have been proposed. Non-specific arm pain (NSAP) is a poorly defined condition, which could benefit from classification according to pain mechanisms to improve treatment selection. This study used three published classification algorithms (hereafter called NeuPSIG, Smart, Schafer) to investigate the frequency of different pain classifications in NSAP and the clinical utility of these systems in assessing NSAP. Forty people with NSAP underwent a clinical examination and quantitative sensory testing. Findings were used to classify participants according to three classification algorithms. Frequency of pain classification including number unclassified was analysed using descriptive statistics. Inter-rater agreement was analysed using kappa coefficients. NSAP was primarily classified as 'unlikely neuropathic pain' using NeuPSIG criteria, 'peripheral neuropathic pain' using the Smart classification and 'peripheral nerve sensitisation' using the Schafer algorithm. Two of the three algorithms allowed classification of all but one participant; up to 45% of participants (n = 18) were categorised as mixed by the Smart classification. Inter-rater agreement was good for the Schafer algorithm (к = 0.78) and moderate for the Smart classification (к = 0.40). A kappa value was unattainable for the NeuPSIG algorithm but agreement was high. Pain classification was achievable with high inter-rater agreement for two of the three algorithms assessed. The Smart classification may be useful but requires further direction regarding the use of clinical criteria included. The impact of adding a pain classification to clinical assessment on patient outcomes needs to be evaluated.

Pain sensitisation and the risk of poor outcome following physiotherapy for patients with moderate to severe knee osteoarthritis: protocol for a prospective cohort study.

INTRODUCTION: Pain is the dominant symptom of knee osteoarthritis (OA), and recent evidence suggests factors outside of local joint pathology, such as pain sensitisation, can contribute significantly to the pain experience. It is unknown how pain sensitisation influences outcomes from commonly employed interventions such as physiotherapy. The aims of this study are, first, to provide a comprehensive description of the somatosensory characteristics of people with pain associated with knee OA. Second, we will investigate if indicators of pain sensitisation in patients with knee osteoarthritis are predictive of non-response to physiotherapy. METHODS AND ANALYSIS: This is a multicentre prospective cohort study with 140 participants. Eligible patients with moderate to severe symptomatic knee osteoarthritis will be identified at outpatient orthopaedic and rheumatology clinics. A baseline assessment will provide a comprehensive description of the somatosensory characteristics of each participant by means of clinical examination, quantitative sensory testing, and validated questionnaires measuring pain and functional capacity. Participants will then undergo physiotherapy treatment. The primary outcome will be non-response to physiotherapy on completion of the physiotherapy treatment programme as defined by the Osteoarthritis Research Society International treatment responder criteria. A principal component analysis will identify measures related to pain sensitisation to include in the predictive model. Regression analyses will explore the relationship between responder status and pain sensitisation while accounting for confounders. ETHICS AND DISSEMINATION: This study has been approved by St James' Hospital/AMNCH Research Ethics Committee and by the St Vincent's Healthcare Group Ethics and Medical Research Committee. The results will be presented at international conferences and published in a peer review journal. TRIAL REGISTRATION NUMBER: NCT02310945.

Reliability of thermal quantitative sensory testing: a systematic review.

The use of quantitative sensory testing (QST) has become more widespread, with increasing focus on describing somatosensory profiles and pain mechanisms. However, the reliability of thermal QST has yet to be established. We systematically searched the literature using key medical databases. Independent reviewers evaluated reliability data using the Quality Appraisal for Reliability Studies checklist. Of the 21 studies we included in this review, we deemed 5 to have high methodological quality. Narrative analysis revealed that estimates of reliability varied considerably, but overall, the reliability of cold and warm detection thresholds ranged from poor to excellent, while heat and cold pain thresholds ranged from fair to excellent. The methodological quality of research investigating the reliability of thermal QST warrants improvement, particularly in terms of appropriate blinding. The results from this review showed considerable variability in the reliability of each thermal QST parameter.