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Supplemental Digital Content is Available in the Text. Anxiety predicts onset of knee pain and drives greater osteoarthritis pain in humans. Our validated preclinical model identifies supraspinal astrocytosis as a potential mechanism., 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.

© 2020 Austin CC et al. The systemic challenges of the COVID-19 pandemic require cross-disciplinary collaboration in a global and timely fashion. Such collaboration needs open research practices and the sharing of research outputs, such as data and code, thereby facilitating research and research reproducibility and timely collaboration beyond borders. The Research Data Alliance COVID-19 Working Group recently published a set of recommendations and guidelines on data sharing and related best practices for COVID-19 research. These guidelines include recommendations for researchers, policymakers, funders, publishers and infrastructure providers from the perspective of different domains (Clinical Medicine, Omics, Epidemiology, Social Sciences, Community Participation, Indigenous Peoples, Research Software, Legal and Ethical Considerations). Several overarching themes have emerged from this document such as the need to balance the creation of data adherent to FAIR principles (findable, accessible, interoperable and reusable), with the need for quick data release; the use of trustworthy research data repositories; the use of well-annotated data with meaningful metadata; and practices of documenting methods and software. The resulting document marks an unprecedented cross-disciplinary, cross-sectoral, and cross-jurisdictional effort authored by over 160 experts from around the globe. This letter summarises key points of the Recommendations and Guidelines, highlights the relevant findings, shines a spotlight on the process, and suggests how these developments can be leveraged by the wider scientific community.

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Background:\ud Knee pain results from a combination of nociceptive input from the joint, and processing by the central nervous system. Pressure pain detection thresholds (PPTs) are lower and pain is more severe in people with greater central sensitisation. \ud \ud Objective:\ud We hypothesised that lower PPTs predicted worse pain prognosis in people with knee pain.\ud \ud Methods:\ud KPIC participants were people aged >40 years recruited from Nottingham, UK. Participants were mailed questionnaires at baseline and 1 year. This study reports a sample of responders who attended baseline and 1 year clinical assessment, had self-reported knee pain (within the last 4 weeks) and underwent PPT. PPTs were measured at the knee, anterior tibia and the sternum. Radiographic knee OA was classified using an atlas. Questionnaires measured ICOAP (constant and intermittent knee pain), painDETECT (neuropathic-like) and average knee pain severity over 4 weeks (0-10).\ud The presence of pain at baseline and 1 year (persistent pain), or pain severity were predicted from baseline anterior tibia PPT. Additional analyses adjusted for baseline pain score, age, sex, BMI, or for radiographic knee OA. Pain persistence (Yes/No) was analysed using t tests, odds ratios (OR) and logistic regression. Pain severity was analysed using linear regression.\ud \ud Results:\ud The sample for this study contained n=419 people at baseline, and n=182 people reported knee pain persistent over both time points. The mean (SD) values were age 61 (9) years, BMI 30.1 (5.8) kg m-2, 59% female, and 36% fulfilled radiographic OA criteria at the index knee, for those with persistent knee pain at 1 year.\ud In univariate analysis, persistent knee pain was associated with a lower PPT at baseline (461 vs 424 kPa; OR (95% CI) 0.58 (0.34-0.97) p=0.020). Adjustments for age, sex and BMI removed the significance from the association (adjusted OR (95% CI) 0.64 (0.36-1.13) p=0.120). \ud In those with persistent pain, worse 1 year ICOAP-constant, ICOAP-intermittent, painDETECT and knee pain severity were correlated with lower baseline anterior tibia PPT ( r= -0.28 to -0.24; p

Introduction: The beneficial effect of dietary omega-3 supplementation in younger adults or older people with acute or chronic disease is established. Knowledge is now needed about the effect in medically stable older people. The objective of this study is to examine and assess the evidence for a role of dietary omega-3 polyunsaturated fatty acid (PUFA) supplementation in older adults on (1) muscle mass and muscle strength, (2) inflammatory biomarkers and (3) physical activity.Methods and analysis: A systematic review and data synthesis will be conducted of randomised controlled trials in older people not recruited for any given disease diagnosis. Placebo-controlled studies reporting interventions involving dietary supplementation of omega-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid will be included. Outcomes must include changes from baseline to last available follow up for one or more of the following: muscle mass, inflammatory biomarkers, physical activity, walking speed, weight change, hand grip strength or muscle strength. Once the search strategy has been carried out, two independent researchers will assess relevant papers for eligibility. Articles up until 31 December 2017 in any language will be included. We will provide a narrative synthesis of the findings from the included studies. Studies will be grouped for meta-analysis according to the outcome(s) provided. Where studies have used the same type of intervention, with the same outcome measure, we will pool the results using a random effects meta-analysis, with standardised mean differences for continuous outcomes and risk ratios for binary outcomes, and calculate 95% CI and two-sided p values for each outcome.Ethics and dissemination: No research ethics approval is required for this systematic review as no confidential patient data will be used. The results of this systematic review will be disseminated through publication in an open-access peer-reviewed journal and through conference presentations.

Ageing is a complex process of accumulation of molecular, cellular, and organ damage, leading to loss of function and increased vulnerability to disease and death, the rate and extent of which varies among individuals. Osteoarthritis (OA) is not only the most common joint disease, but is also one of the major causes of disability in people aged >65 years and is accompanied by comorbid conditions, increased mortality, and decreased quality of life. One of the major risk factors for OA is ageing. However, OA itself may be involved in the biological ageing process. This is likely to be in part a direct involvement, by contributing levels of systemic inflammation and sharing molecular pathways with biological ageing, such as mitochondrial damage leading to cell senescence. Although OA is not considered an inflammatory form of arthritis, there is evidence of subclinical low-grade inflammation in the whole joint and inflammatory processes play a key role in the disease pathogenesis. For instance, there is synovial inflammation (e.g., following injury), mechanically derived inflammation present due to biomechanical overloading of a joint, and systemic inflammation resulting from obesity. Systemic inflammation is often associated with frailty, and having a high concentration of inflammatory markers is predictive of incident frailty, some of which are known to increase with age and correlate with pain. In addition, OA may also contribute indirectly to biological ageing via the disability and pain resulting from it. Further research into the exact process linking OA and biological ageing, including frailty, is needed.

PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) 2015 checklist: recommended items to address in a systematic review protocol*. (DOC 895 kb)