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Objective: This observational study investigated whether central aspects of pain are associated with self-management domains in individuals with chronic low back pain (CLBP) undertaking a pain management program., Methods: Individuals with CLBP provided pain sensitivity and self-management data at baseline (n = 97) and 3-months (n = 87). Pressure pain detection threshold (PPT) at the forearm, temporal summation (TS) and conditioned pain modulation (CPM), Widespread Pain Index (WPI), and a Central Aspects of Pain factor (CAPf) were considered as central aspects of pain. Self-management was measured using the 8 domains of the Health Education Impact Questionnaire, as well as Pain Self Efficacy and Health Care Utilisation questionnaires., Results: PPT, CPM, WPI and CAPf predicted worse performance in several self-management domains at 3-months (r = 0.21 to 0.54, p < 0.05 overall). In multivariable regression models (adjusted for baseline scores of self-management, depression, catastrophization, pain and fatigue) low PPT, high TS, and high CAPf at baseline predicted poorer self-management at 3 months (R 2 =0.14 to 0.52, β = -0.37 to 0.35, p < 0.05)., Conclusions: Central aspects of pain are associated with impaired self-management, over and above effects of pain intensity, fatigue, depression and catastrophizing., Practice Implications: Treatments that target central aspects of pain might help improve self-management in people with CLBP., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof David Walsh has received research grants from Pfizer Ltd., Eli Lilly, Orion Pharma, UCB Pharma and non-personal pecuniary consultancy fees from GlaxoSmithKline plc, AKL Research & Development Limited, Pfizer Ltd, Eli Lilly and Company, Galapagos, Contura International, and AbbVie Ltd. Dr Daniel McWilliams has received research grants from Pfizer Ltd. And Eli Lilly. Dr Paul Hendrick and Dr Vasileios Georgopoulos have no relevant interests to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Pain and frailty are closely linked. Chronic pain is a risk factor for frailty, and frailty is a risk factor for pain. People living with frailty also commonly have cognitive impairment, which can make assessment of pain and monitoring of pain management even more difficult. Pain may be sub-optimally treated in people living with frailty, people living with cognitive impairment and those with both these factors. Reasons for sub-optimal treatment in these groups are pharmacological (increased drug side effects, drug-drug interactions, polypharmacy), non-pharmacological (erroneous beliefs about pain, ageism, bidirectional communication challenges), logistical (difficulty in accessing primary care practitioners and unaffordable cost of drugs), and, particularly in cognitive impairment, related to communication difficulties. Thorough assessment and characterisation of pain, related sensations, and their functional, emotional, and behavioural consequences ("phenotyping") may help to enhance the assessment of pain, particularly in people with frailty and cognitive impairment, as this may help to identify who is most likely to respond to certain types of treatment. This paper discusses the potential role of "digital phenotyping" in the assessment and management of pain in people with frailty. Digital phenotyping is concerned with observable characteristics in digital form, such as those obtained from sensing-capable devices, and may provide novel and more informative data than existing clinical approaches regarding how pain manifests and how treatment strategies affect it. The processing of extensive digital and usual data may require powerful algorithms, but processing these data could lead to a better understanding of who is most likely to benefit from specific and targeted treatments., (© 2024. The Author(s).)

Objective: Despite the high prevalence of chronic low back pain (CLBP) and osteoarthritis (OA), few estimates of the economic cost of these conditions in England have been published. The aim of the present analysis was to characterise the economic burden of moderate-to-severe pain associated with CLBP + OA and CLBP alone compared with general population-matched controls without CLBP or OA. The primary objective was to describe the total healthcare resource use (HCRU) and direct healthcare costs associated with the target patient populations. Secondary objectives were to describe treatment patterns and surgical procedures., Methods: This was a retrospective, observational cohort study of patients receiving healthcare indicative of moderate-to-severe chronic pain associated with CLBP, with or without OA. We used linked longitudinal data from the Clinical Practice Research Datalink GOLD and Hospital Episode Statistics (HES). Patients (cases) were matched 1 : 1 with controls on age, sex, comorbidity burden, GP practice, and HES data availability., Results: The CLBP-alone cohort comprised 13 554 cases with CLBP and 13 554 matched controls; the CLBP + OA cohort comprised 7803 cases with both OA and CLBP and 7803 matched controls. Across all follow-up periods, patients with CLBP alone and those with CLBP + OA had significantly more GP consultations, outpatient attendances, emergency department visits, and inpatient stays than controls (all p  < 0.0001). By 36 months after indexing, the mean (SD) per-patient total direct healthcare cost in the CLBP-alone cohort was £5081 (£5905) for cases and £1809 (£4451) for controls ( p  < 0.0001); in the CLBP + OA cohort, the mean (SD) per-patient total direct healthcare cost was £8819 (£7143) for cases and £2428 (£4280) for controls ( p  < 0.0001)., Conclusion: Moderate-to-severe chronic pain associated with CLBP-with or without OA-has a substantial impact on patients and healthcare providers, leading to higher HCRU and costs versus controls among people with CLBP alone or together with OA., Competing Interests: GC and PC are employees of Pfizer UK. CL was an employee of Pfizer UK at the time of the work and is now employed by Pfizer Aus. HS was an employee of Pfizer UK during the conduct of the work. RW and TT are employees of Adelphi Real World, which was contracted by Pfizer UK to conduct this study. RDK declares a personal financial interest in his employment by the University of Nottingham, which receives funding for his salary in part from the Primary Integrated Community Solutions Ltd. In the past 36 months, RDK declares the following nonpersonal financial interests: consultancy through his employment with the University of Nottingham to Pfizer Ltd. and Mibe Ltd. AJD declares a personal financial interest in his employment with York Medical Group (YMG), and over the past 36 months with NHS111 and RCP (London), from whom he receives payment for his work as a part-time salaried GP with YMG, and over the past 36 months as a GP on the NHS111 COVID-19 Response and the NICE Gout Committee, respectively, and in his ownership and directorship of AD Outcomes Ltd. In the past 36 months, AJD declares the following personal financial interests through medical and health economics consultancy work for AD Outcomes Ltd. for: Emotive (Agency) Ltd., Grunenthal (UK), Grunenthal (GmbH), Pfizer (UK), Pharmacy Magazine, Spink Health, Tilray (Portugal), and RCGP, as a racecourse doctor for various racecourses (Croft, Doncaster, Market Rasen, Newcastle, Pontefract, Redcar, Southwell, and Thirsk), and as a locum GP with out-of-hours, NHS111 and urgent care work for Vocare part of Totally Plc. AJD has a nonpersonal financial interest in his roles as a Trustee of the Primary Care Rheumatology and Musculoskeletal Medicine (PCRMM) Society (Trustee from 2017 to 2020) and as Trustee of the UK Gout Society (ongoing). The PCRMM Society has received funding from multiple companies for its annual conference including from Pfizer (UK) in 2020. AJD's work as a Trustee of the PCRMM Society and the UK Gout Society and as GP Clinical Lead for the North of England Low Back Pain Group are voluntary and unpaid; DAW declares a personal financial interest in his employment by the University of Nottingham, which receives funding for his salary from the UK Government, Sherwood Forest Hospitals NHS Foundation Trust, and UKRI. He is Director of the UKRI/Versus Arthritis Advanced Pain Discovery Platform (personal pecuniary: paid by the University of Nottingham as part of job plan, funded by UKRI), Honorary Consultant Rheumatologist at Sherwood Forest Hospitals NHS Foundation Trust (personal pecuniary; paid by the University of Nottingham as part of job plan, funded by Sherwood Forest Hospitals), and Professor of Rheumatology, University of Nottingham (personal pecuniary; paid by the University of Nottingham). In the past 36 months, DAW declares the following nonpersonal financial interests: research support to the University of Nottingham from Versus Arthritis and National Institute for Health and care Research; grants from Pfizer Ltd., Eli Lilly, and UCB Pharma; consultancy through his employment with the University of Nottingham to Pfizer Ltd., Eli Lilly, AbbVie Ltd., AKL R&D, Galapagos, Reckitt Benckiser Health Ltd., and GlaxoSmithKline Plc, and responsibilities for investigator-led grants outside the work in this presentation held by the University of Nottingham from Pfizer Ltd., Lilly Ltd. and UCB Pharma, and research grants from Versus Arthritis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (to University of Nottingham) from Pfizer Ltd. and AbbVie. The authors declare that they have no conflicts of interest., (Copyright © 2023 Greg Coates et al.)

Pain is common in people with dementia, and pain can exacerbate the behavioural and psychological symptoms of dementia. Effective pain management is challenging, not least in people with dementia. Impairments of cognition, communication and abstract thought can make communicating pain unreliable or impossible. It is unclear which biopsychosocial interventions for pain management are effective in people with dementia, and which interventions for behavioural and psychological symptoms of dementia are effective in people with pain. The result is that drugs, physical therapies and psychological therapies might be either underused or overused. People with dementia and pain could be helped by assessment processes that characterise an individual's pain experience and dementia behaviours in a mechanistic manner, phenotyping. Chronic pain management has moved from a 'one size fits all' approach, towards personalised medicine, where interventions recommended for an individual depend upon the key mechanisms underlying their pain, and the relative values they place on benefits and adverse effects. Mechanistic phenotyping through careful personalised evaluation would define the mechanisms driving pain and dementia behaviours in an individual, enabling the formulation of a personalised intervention strategy. Central pain processing mechanisms are particularly likely to be important in people with pain and dementia, and interventions to accommodate and address these may be particularly helpful, not only to relieve pain but also the symptoms of dementia., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The reciprocal interaction between pain and negative affect is acknowledged but pain-related alterations in brain circuits involved in this interaction, such as the mediodorsal thalamus (MDThal), still require a better understanding. We sought to investigate the relationship between MDThal circuitry, negative affect and pain severity in chronic musculoskeletal pain. For these analyses, participants with chronic knee pain (CKP, n = 74) and without (n = 36) completed magnetic resonance imaging scans and questionnaires. Seed-based MDThal functional connectivity (FC) was compared between groups. Within CKP group, we assessed the interdependence of MDThal FC with negative affect. Finally, post hoc moderation analysis explored whether burden of pain influences affect-related MDThal FC. The CKP group showed altered MDThal FC to hippocampus, ventromedial prefrontal cortex and subgenual anterior cingulate. Furthermore, in CKP group, MDThal connectivity correlated significantly with negative affect in several brain regions, most notably the medial prefrontal cortex, and this association was stronger with increasing pain burden and absent in pain-free controls. In conclusion, we demonstrate mediodorsal thalamo-cortical dysconnectivity in chronic pain with areas linked to mood disorders and associations of MDThal FC with negative affect. Moreover, burden of pain seems to enhance affect sensitivity of MDThal FC. These findings suggest mediodorsal thalamic network changes as possible drivers of the detrimental interplay between chronic pain and negative affect., (© 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Several pharmaceutical treatments for chronic pain caused by osteoarthritis (OA) and chronic low back pain (CLBP) are available or currently under development, each associated with different adverse events (AEs) and efficacy profiles. It is therefore important to understand what trade-offs patients are willing to make when choosing between treatments., Methods: A discrete-choice experiment (DCE) was conducted with 437 adults with chronic pain caused by OA and/or CLBP. Respondents were presented with a series of scenarios and asked to choose between pairs of hypothetical treatments, each defined by six attributes: level of symptom control; risks of heart attack, rapidly progressive osteoarthritis and dependency; frequency and mode of administration and cost. Attributes were based on known profiles of oral nonsteroidal anti-inflammatory drugs, opioids and injected nerve growth factor inhibitors, the last of which were under clinical development at the time of the study. Data were analysed using a latent class (LC) model to explore preference heterogeneity., Results: Overall, respondents considered improving symptom control and reducing risk of physical dependency to be the most important attributes. The LC analysis identified four participant classes: an 'efficacy-focused' class (33.7%), a 'cost-averse' class (29.4%), a 'physical-dependence-averse' class (19.6%) and a 'needle-averse' class (17.3%). Subgroup membership was incompletely predicted by participant age and their responses to comprehension questions., Conclusions: Preference heterogeneity across respondents indicates a need for a personalized approach to offering treatment options. Symptom improvement, cost, physical dependence and route of administration might be important to different patients., Significance: Multiple treatment options that differ substantially in terms of efficacy and adverse events are available for the management of chronic pain. With a growing emphasis on a patient-centred care model that incorporates patients' priorities and values into treatment decisions, there is a need to understand how individuals with chronic musculoskeletal pain balance the benefits and risks of treatment and how treatment priorities vary among individuals. This study was designed to identify patient preferences for different characteristics of treatments for the management of chronic pain and to investigate how preferences differ among respondents., (© 2021 Pfizer Inc. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.)

Background: Knee pain is a major source of distress and disability, with pain progression highly variable between individuals. Previous studies defining pain trajectories have all used a single measure of pain, and these differ across studies. Different measures reflect diverse pain mechanisms. To ascertain the clinical utility of pain trajectories, we explored associations between opioid and non-steroidal anti-inflammatory drug (NSAID) use., Methods: We model pain trajectories using two measures-Intermittent and Constant Osteoarthritis Pain (ICOAP) and the painDETECT, in 2141 participants, across 3 waves (the baseline, 1- and 3-year assessments) of the Knee Pain In the Community (KPIC) cohort., Results: Latent class growth analysis identified six trajectories using ICOAP subscales (High-Stable, Low-Stable, Moderate Worsening, Moderate Recovering, Worsening, and Recovering) and four trajectories using painDETECT (High-stable, Low-stable, Moderate Worsening, and Moderate Recovering). There was a high degree of correspondence between people assigned to pain trajectories between ICOAP intermittent and constant subscales, but less so using painDETECT. Opioid use was associated with ICOAP trajectories only (e.g., High-Stable and Worsening intermittent ICOAP trajectories) and in women., Conclusion: Different measures of pain produce different patterns of pain progression and these are differentially related to medication use. Opioid use is linked to trajectories of pain based on the impact of pain on behavior and not pain symptoms. Thus, managing pain's behavioral impact is more central to understanding opioid use than managing pain symptoms. These findings support more in-depth questioning about the type of pain and its progression in clinical practice., (© 2021 World Institute of Pain.)

Brain-derived neurotrophic factor (BDNF) and the high-affinity receptor tropomyosin receptor kinase B (TrkB) have important roles in neuronal survival and in spinal sensitization mechanisms associated with chronic pain. Recent clinical evidence also supports a peripheral role of BDNF in osteoarthritis (OA), with synovial expression of TrkB associated with higher OA pain. The aim of this study was to use clinical samples and animal models to explore the potential contribution of knee joint BDNF/TrkB signalling to chronic OA pain. Brain-derived neurotrophic factor and TrkB mRNA and protein were present in knee synovia from OA patients (16 women, 14 men, median age 67 years [interquartile range: 61-73]). There was a significant positive correlation between mRNA expression of NTRK2 (TrkB) and the proinflammatory chemokine fractalkine in the OA synovia. Using the surgical medial meniscal transection (MNX) model and the chemical monosodium iodoacetate (MIA) model of OA pain in male rats, the effects of peripheral BDNF injection, vs sequestering endogenous BDNF with TrkB-Fc chimera, on established pain behaviour were determined. Intra-articular injection of BDNF augmented established OA pain behaviour in MIA rats, but had no effect in controls. Intra-articular injection of the TrkB-Fc chimera acutely reversed pain behaviour to a similar extent in both models of OA pain (weight-bearing asymmetry MIA: -11 ± 4%, MNX: -12 ± 4%), compared to vehicle treatment. Our data suggesting a contribution of peripheral knee joint BDNF/TrkB signalling in the maintenance of chronic OA joint pain support further investigation of the therapeutic potential of this target.

Anxiety and depression are associated with increased pain responses in chronic pain states. The extent to which anxiety drives chronic pain, or vice versa, remains an important question that has implications for analgesic treatment strategies. Here, the effect of existing anxiety on future osteoarthritis (OA) pain was investigated, and potential mechanisms were studied in an animal model. Pressure pain detection thresholds, anxiety, and depression were assessed in people with (n = 130) or without (n = 100) painful knee OA. Separately, knee pain and anxiety scores were also measured twice over 12 months in 4730 individuals recruited from the general population. A preclinical investigation of a model of OA pain in normo-anxiety Sprague-Dawley (SD) and high-anxiety Wistar Kyoto (WKY) rats assessed underlying neurobiological mechanisms. Higher anxiety, independently from depression, was associated with significantly lower pressure pain detection thresholds at sites local to (P < 0.01) and distant from (P < 0.05) the painful knee in patients with OA. Separately, high anxiety scores predicted increased risk of knee pain onset in 3274 originally pain-free people over the 1-year period (odds ratio = 1.71; 95% confidence interval = 1.25-2.34, P < 0.00083). Similarly, WKY rats developed significantly lower ipsilateral and contralateral hind paw withdrawal thresholds in the monosodium iodoacetate model of OA pain, compared with SD rats (P = 0.0005). Linear regressions revealed that baseline anxiety-like behaviour was predictive of lowered paw withdrawal thresholds in WKY rats, mirroring the human data. This augmented pain phenotype was significantly associated with increased glial fibrillary acidic protein immunofluorescence in pain-associated brain regions, identifying supraspinal astrocyte activation as a significant mechanism underlying anxiety-augmented pain behaviour.

Background: Approximately 20% of patients experience chronic pain after total knee replacement. There is little evidence for effective interventions for the management of this pain, and current healthcare provision is patchy and inconsistent. Given the complexity of this condition, multimodal and individualised interventions matched to pain characteristics are needed. We have undertaken a comprehensive programme of work to develop a care pathway for patients with chronic pain after total knee replacement. This protocol describes the design of a randomised controlled trial to evaluate the clinical- and cost-effectiveness of a complex intervention care pathway compared with usual care., Methods: This is a pragmatic two-armed, open, multi-centred randomised controlled trial conducted within secondary care in the UK. Patients will be screened at 2 months after total knee replacement and 381 patients with chronic pain at 3 months postoperatively will be recruited. Recruitment processes will be optimised through qualitative research during a 6-month internal pilot phase. Patients are randomised using a 2:1 intervention:control allocation ratio. All participants receive usual care as provided by their hospital. The intervention comprises an assessment clinic appointment at 3 months postoperatively with an Extended Scope Practitioner and up to six telephone follow-up calls over 12 months. In the assessment clinic, a standardised protocol is followed to identify potential underlying causes for the chronic pain and enable appropriate onward referrals to existing services for targeted and individualised treatment. Outcomes are assessed by questionnaires at 6 and 12 months after randomisation. The co-primary outcomes are pain severity and pain interference assessed using the Brief Pain Inventory at 12 months after randomisation. Secondary outcomes relate to resource use, function, neuropathic pain, mental well-being, use of pain medications, satisfaction with pain relief, pain frequency, capability, health-related quality of life and bodily pain. After trial completion, up to 30 patients in the intervention group will be interviewed about their experiences of the care pathway., Discussion: If shown to be clinically and cost-effective, this care pathway intervention could improve the management of chronic pain after total knee replacement., Trial Registration: ISRCTN registry ( ISRCTN92545361 ), prospectively registered on 30 August 2016.

Introduction: Osteoarthritis (OA) pain is a major cause of long-term disability and chronic pain in the adult population. One in five patients does not receive satisfactory pain relief, which reflects the complexity of chronic pain and the current lack of understanding of mechanisms of chronic pain. Recently, duloxetine has demonstrated clinically relevant pain relief, but only in half of treated patients with OA. Here, the aim is to investigate the neural mechanisms of pain relief and neural signatures that may predict treatment response to duloxetine in chronic knee OA pain., Methods and Analysis: This is an ongoing single-centre randomised placebo-controlled mechanistic study (2:1 (placebo) allocation), using a multimodal neuroimaging approach, together with psychophysiological (quantitative sensory testing), genetics and questionnaire assessments. Eighty-one subjects with chronic knee OA pain are planned to power for between-group comparisons (placebo, duloxetine responder and duloxetine non-responder). Participants have a baseline assessment and, following 6 weeks of duloxetine (30 mg for 2 weeks, then 60 mg for 4 weeks), a follow-up evaluation. Brain imaging is performed at 3T with blood-oxygen-level dependent functional MRI at rest and during pin-prick nociceptive stimulation for main outcome assessment; arterial spin labelling and structural imaging (T1-weighted) for secondary outcome assessment. Questionnaires evaluate pain, negative affect, quality of sleep and cognition., Ethics and Dissemination: The study has been approved by the East Midlands, Nottingham and is being carried out under the principles of the Declaration of Helsinki (64th, 2013) and Good Clinical Practice standards. Results will be disseminated in peer-reviewed journals and at scientific conferences., Trial Registration Number: This trial is registered at ClinicalTrials.gov (NCT02208778).This work was supported by Arthritis Research UK (Grant 18769)., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To examine the measurement properties of the Chronic Pain Acceptance Questionnaire Revised (CPAQ-R) and its subscales with people with knee osteoarthritis using Rasch analysis., Design: Cross-sectional questionnaire study., Patients: A total of 176 participants with radiographic evidence of osteoarthritis of the knee, as identified by a Kellgren-Lawrence grade ≥ 2, and pain on most days for at least the past month., Methods: Participants completed the CPAQ-R at home within a set of measures covering different aspects of osteoarthritis pain. The questionnaires were returned by pre-paid envelope. Rasch analysis was conducted on the Activity Engagement and Pain Willingness subscales and the Total scale using Rasch Unidimensional Measurement Models (RUMM2020)., Results: The Activity Engagement and Pain Willingness subscales fit the Rasch model following minimal changes, including re-scoring and removal of item 14 due to misfit. Both subscales passed tests of unidimensionality. Although the Total scale could be adjusted to yield adequate fit statistics, it demonstrated multidimensionality., Conclusion: The Activity Engagement and Pain Willingness subscales have good measurement properties for 2 distinct factors relevant to pain acceptance. CPAQ-R is a valid measurement tool that may help target and evaluate response to treatments that address low activity engagement and pain willingness in people with osteoarthritis.

ObjectiveChronic pain due to osteoarthritis (OA) is a major clinical problem, and existing analgesics often have limited beneficial effects and/or adverse effects, necessitating the development of novel therapies. Epoxyeicosatrienoic acids (EETs) are endogenous antiinflammatory mediators, rapidly metabolized by soluble epoxide hydrolase (EH) to dihydroxyeicosatrienoic acids (DHETs). We undertook this study to assess whether soluble EH-driven metabolism of EETs to DHETs plays a critical role in chronic joint pain associated with OA and provides a new target for treatment.MethodsPotential associations of chronic knee pain with single-nucleotide polymorphisms (SNPs) in the gene-encoding soluble EH and with circulating levels of EETs and DHETs were investigated in human subjects. A surgically induced murine model of OA was used to determine the effects of both acute and chronic selective inhibition of soluble EH by N-[1-(1-oxopropy)-4-piperidinyl]-N'-(trifluoromethoxy)phenyl]-urea (TPPU) on weight-bearing asymmetry, hind paw withdrawal thresholds, joint histology, and circulating concentrations of EETs and DHETs.ResultsIn human subjects with chronic knee pain, 3 pain measures were associated with SNPs of the soluble EH gene EPHX2, and in 2 separate cohorts of subjects, circulating levels of EETs and DHETs were also associated with 3 pain measures. In the murine OA model, systemic administration of TPPU both acutely and chronically reversed established pain behaviors and decreased circulating levels of 8,9-DHET and 14,15-DHET. EET levels were unchanged by TPPU administration.ConclusionOur novel findings support a role of soluble EH in OA pain and suggest that inhibition of soluble EH and protection of endogenous EETs from catabolism represents a potential new therapeutic target for OA pain.

Background: The Support and Treatment After Replacement (STAR) care pathway is a clinically important and cost-effective intervention found to improve pain outcomes over one year for people with chronic pain three months after total knee replacement (TKR). We followed up STAR trial participants to evaluate the longer-term clinical- and cost-effectiveness of this care pathway. Methods: Participants who remained enrolled on the trial at one year were contacted by post at a median of four years after randomisation and invited to complete a questionnaire comprising the same outcomes collected during the trial. We captured pain (co-primary outcome using the Brief Pain Inventory (BPI) pain severity and interference scales; scored 0–10, best to worst), function, neuropathic characteristics, emotional aspects of pain, health-related quality of life, and satisfaction. Electronic hospital informatics data on hospital resource use for the period of one to four years post-randomisation were collected from participating hospital sites. The economic evaluation took an National Health Service (NHS) secondary care perspective, with a four-year time horizon. Results: Overall, 226/337 (67%) of participants returned completed follow-up questionnaires, yielding adjusted between-group differences in BPI means of -0.42 (95% confidence interval, CI (-1.07, 0.23); p = 0.20) for pain severity and − 0.64 (95% CI -1.41, 0.12); p = 0.10) for pain interference. Analysis using a multiple imputed data set (n = 337) showed an incremental net monetary benefit in favour of the STAR care pathway of £3,525 (95% CI -£990 to £8,039) at a £20,000/QALY willingness-to-pay threshold, leading to a probability that the intervention was cost-effective of 0.94. Conclusions: The magnitude of the longer-term benefits of the STAR care pathway are uncertain due to attrition of trial participants; however, there is a suggestion of some degree of sustained clinical benefit at four years. The care pathway remained cost-effective at four years. Trial registration: ISRCTN: 92,545,361. [ABSTRACT FROM AUTHOR]

Purpose: To examine the fit between data from the Short Form McGill Pain Questionnaire (SF-MPQ-2) and the Rasch model, and to explore the reliability and internal responsiveness of measures of pain in people with knee osteoarthritis. Methods: Participants with knee osteoarthritis completed the SF-MPQ-2, Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP) and painDETECT. Participants were sent the same questionnaires 3 and 6 months later. Results: Fit to the Rasch model was not achieved for the SF-MPQ-2 Total scale. The Continuous subscale yielded adequate fit statistics after splitting item 10 on uniform DIF for gender, and removing item 9. The Intermittent subscale fit the Rasch model after rescoring items. The Neuropathic subscale had relatively good fit to the model. Test-retest reliability was satisfactory for most scales using both original and Rasch scoring ranging from fair to substantial. Effect sizes ranged from 0.13 to 1.79 indicating good internal responsiveness for most scales. Conclusions: These findings support the use of ICOAP subscales as reliable and responsive measure of pain in people with knee osteoarthritis. The MPQ-SF-2 subscales found to be acceptable alternatives. [ABSTRACT FROM AUTHOR]

Background: Knee replacement surgery reduces pain for many people with osteoarthritis (OA). However, surgical outcomes are partly dependent on patients' moods, and those with depression or anxiety have worse outcomes. Approximately one-third of people with OA have mood problems. Cognitive behavioural therapy (CBT), a psychological therapy, is recommended by the National Institute for Health and Care Excellence for improving mood. However, evidence for the effectiveness of CBT before knee surgery in improving pain, mood, and quality of life following this surgery for people with knee OA is lacking.Methods/design: This is a multi-centre, mixed-methods feasibility randomised controlled trial to compare treatment as usual (TAU) plus a brief CBT-based intervention with a TAU-only control, for people with knee OA. We will recruit 50 patients with knee OA, listed for knee replacement surgery, with high levels of distress (assessed using a mood questionnaire), and who consent to take part. Participants will be randomly allocated to receive TAU plus intervention or TAU. Up to 10 sessions of CBT will be offered on an individual basis by a psychologist. The assessments and interventions will be completed before surgery. Repeat assessments at 4 and 6 months after randomisation will be sent and received by post. Two patient-partners will conduct feedback interviews with some participants to assess what aspects of the intervention were helpful or unhelpful, the acceptability of randomisation, the experience of being in a control group, and the appropriateness of the measures used. Interviews will be audio-recorded, transcribed, and analysed using the framework approach. We will examine the feasibility and acceptability of patient-partners conducting the interviews by also interviewing the patient-partners.Discussion: Findings from this study will be used to design a definitive study that will examine the clinical and cost-effectiveness of the CBT intervention in improving patient outcomes following knee surgery.Trial Registration: Current Controlled Trials ISRCTN80222865; Date: 19 June 2014. [ABSTRACT FROM AUTHOR]

Cognitive–behavioural therapy and maintenance of exercise have emerged as major tools in the treatment of patients with chronic low back pain. Patients'' beliefs about their problem may influence their uptake of and responses to particular treatment modalities. In particular, we hypothesised that patients'' beliefs about the cause and treatment of pain may mediate changes in physical disability following participation in a multidisciplinary pain management programme. A cohort of 84 patients was invited to respond to booklets of self-report questionnaires prior to, immediately after and 3 months following participation in multidisciplinary pain management programmes. Questionnaires addressed subjects'' beliefs about the nature and treatment of pain (Pain Beliefs Questionnaire), and their disability (Likert-modified Roland and Morris Disability Questionnaire, Physical Functioning scale of the Short Form-36 Health Survey, and Oswestry Low Back Pain Disability Questionnaire). Patients with chronic low back pain who more strongly endorsed ‘organic’ concepts about the nature and treatment of pain reported higher levels of physical disability at baseline, and displayed greater reductions in disability following participation in the pain management programmes. Reductions in reported ‘organic’ pain beliefs were associated with improvements in reported disability. Endorsement of ‘psychological’ concepts about the nature and treatment of pain was not associated with disability. These findings support a view that patients'' beliefs about the nature and treatment of their pain can change during participation in a multidisciplinary pain management programme based on cognitive–behavioural intervention. Modification of these beliefs may be associated with improvements in patients'' perceptions of the level of their disability. [Copyright &y& Elsevier]

Chronic musculoskeletal pain is a common problem globally. Current evidence suggests that maladapted central pain pathways are associated with pain chronicity, for example, in postoperative pain after knee replacement. Other factors such as low mood, anxiety, and tendency to catastrophize are also important contributors. We aimed to investigate brain imaging features that underpin pain chronicity based on multivariate pattern analysis of cerebral blood flow (CBF), as a marker of maladaptive brain changes. This was achieved by identifying CBF patterns that discriminate chronic pain from pain-free conditions and by exploring their explanatory power for factors thought to drive pain chronification. In 44 chronic knee pain and 29 pain-free participants, we acquired both CBF and T1-weighted data. Participants completed questionnaires related to affective processes and pressure and cuff algometry to assess pain sensitization. Two factor scores were extracted from these scores representing negative affect and pain sensitization. A spatial covariance principal component analysis of CBF identified 5 components that significantly discriminated chronic pain participants from controls, with the unified network achieving 0.83 discriminatory accuracy (area under the curve). In chronic knee pain, significant patterns of relative hypoperfusion were evident in anterior default-mode and salience network hubs, while hyperperfusion was seen in posterior default mode, thalamus, and sensory regions. One component correlated positively with the pain sensitization score (r = 0.43, P = 0.006), suggesting that this CBF pattern reflects neural activity changes encoding pain sensitization. Here, we report a distinct chronic knee pain-related representation of CBF, pointing toward a brain signature underpinning central aspects of pain sensitization. [ABSTRACT FROM AUTHOR]

The article compares beliefs on the consequences and causes of pain in pain-free individuals and patients with chronic non-inflammatory or inflammatory low back pain (LBP). Also explored is the difference in pain beliefs between patients with chronic LBP and pain-free controls and between patients with chronic LBP attributed to non-inflammatory or inflammatory medical diagnoses. Also cited are the issues' implications for studies of the spine.