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with increasing pain severity. In participants without pain, there were no major differences in PSS between people that did or did not perform sports. In contrast, in participants that did have current pain, performing sports revealed a lower PSS than not performing sports in both genders. The different films did not affect the pain sensitivity score in male participants. In females the film with laughing people led to a slightly lower PSS. However, the largest effect of film was observed in females who saw a film with people in pain. This led to an unexpected lower PSS than in females who did not see a film (55 vs 63, p<0,000). Conclusions: Our Dutch population study revealed that current pain had the largest impact on pain sensitivity. This effect was even larger in women as compared to men. We showed that females have a higher pain sensitivity than males. Importantly, our study shows that performing sports is related to lower pain sensitivity in people with pain. In females we found that changing environmental factors might be of larger benefit to influence pain than in males, as shown by the effect of watching different short films prior to filling out the questionnaires. In conclusion, our study shows that indeed pain severity has a major impact on pain sensitivity, but pain sensitivity is also subject to other factors like for example gender and sports. The latter strengthens findings of positive effects of sports that were found in OA pain as well. In females there is an added complexity due to a larger effect of external stimuli on pain sensitivity. Together with the differences in pain sensitivity between males and females this underlines the importance of gender differentiation in pain research.Purpose: Subchondral bone contributes to pain in knee osteoarthritis (OA). OA structural change particularly affects weight-bearing components of the joint, most notably the medial femorotibial compartment in people with varus angulation. Subchondral bone marrow lesions (BMLs) detected on MRI in knee OA are strongly associated with pain. BMLs typically occur in regions of the joint with the most severe structural change, for example, full-thickness cartilage lesions. However, the association between subchondral BMLs in weight-bearing components and weight-bearing pain has not been clarified. The purpose of this study was to assess association between BMLs location and weight bearing knee pain using data from the Osteoarthritis Initiative (OAI). We hypothesized that BMLs at the medial femorotibial joint compartment were associated with weight bearing pain, independent of non-weight bearing pain, and that changes in size of the BMLs over time were associated with change in weight bearing pain. Methods: The OAI is a publicly available multi-center, longitudinal, prospective observational study of knee OA. We examined the knees of OAI participants with MRI readings using the MRI Osteoarthritis Knee Score (MOAKS). BMLs, articular cartilage, osteophytes, Hoffa's synovitis, effusion, meniscal morphology and anterior cru...

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Background Subchondral bone marrow lesions (BMLs) detected on MRI in knee osteoarthritis (OA) are associated with knee pain. The prevalence and progression of subchondral BMLs are increased by mechanical knee load. However, associations of subchondral BML location with weight-bearing knee pain are currently unknown. In this study, we aim to demonstrate associations of subchondral BML location and size with weight-bearing knee pain in knee OA.Methods We analyzed 1412 and 582 varus knees from cross-sectional and longitudinal Osteoarthritis Initiative datasets, respectively. BML scores were semi-quantitatively analysed with the MRI Osteoarthritis Knee Score for 4 subchondral regions (median and lateral femorotibial, medial and lateral patellofemoral) and subspinous region. Weight-bearing and non-weight-bearing pain scores were derived from WOMAC pain items. Correlation and negative binomial regression models were used for analysis of associations between the BML scores and pain at baseline, and changes in the BML scores and changes in pain after 24-month follow up.Results Greater BML scores at medial femorotibial and lateral patellofemoral compartments were associated with greater weight-bearing pain scores, and statistical significance was retained after adjusting for BML scores at the other 4 joint compartments and other OA features, as well as for non-weight-bearing pain, age, sex and Body Mass Index (BMI) (medial femorotibial; B=0.08, p=0.02. patellofemoral; B=0.13, p=0.01). Subanalysis revealed that greater medial femorotibial BML scores were associated with greater pain on walking and standing (B=0.11, p=0.01, and B=0.10, p=0.04, respectively). Lateral patellofemoral BML scores were associated with pain on climbing, respectively B=0.14, p=0.02. Increases or decreases over 24 months in BML score in the medial femorotibial compartment were significantly associated with increases or decreases in weight-bearing pain severity after adjusting for non-weight-bearing pain, age, sex, baseline weight-bearing pain, BMI, and BML at the other 4 joint compartments (B=0.10, p=0.01). Conclusions Subchondral BML size at the medial femorotibial joint compartment was specifically associated with the severity and the change in weight-bearing pain, independent of non-weight-bearing pain, in knee OA. Specific associations of weight-bearing pain with subchondral BMLs in weight-bearing compartments of the knee indicate that BMLs in subchondral bone contribute to biomechanically-induced OA pain.