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Introduction: Chronic pain in breast cancer survivors (BCSs) impacts the health-related quality of life (HRQoL) and participation in activities of daily living tremendously[1-5]. Over the past decades, the use of pain neuroscience education (PNE) has been shown to be effective in reducing pain[6-8]. Since PNE alone has relatively small effect sizes, it should ideally be combined with a physical component[6], such as behavioural graded activity (BGA)[9,10]. Therefore, this study aims to investigate the effectiveness of PNE with BGA compared to usual care on chronic pain in BCSs. Methods: Two hundred BCSs with chronic pain will be randomly assigned to the intervention or usual care group. The intervention group will receive a 12-week treatment program consisting of 6 sessions, in which PNE and BGA are integrated. Whereas the usual care group will receive an information leaflet regarding "Pain in and after cancer". The primary outcome is pain, and the secondary outcomes are endogenous hyperalgesia and HRQoL. Explanatory variables such as pain cognitions, sleep, depression will be inventoried as well. All variables will be assessed at baseline, immediate, 3-and, 12-months post-treatment. To examine the added effect of PNE and BGA, a linear mixed model for repeated measurements will be conducted[11,12]. Results: We hypothesise that PNE with BGA will lead to more beneficial outcomes compared to usual care in BCSs with chronic pain. Discussion: PNE with BGA might lead to proper non-pharmacological treatment for pain in BCS. Process evaluation: Currently, 82/200 participants were recruited. The recruitment was delayed due to the COVID-19 outbreak. [ABSTRACT FROM AUTHOR]

Introduction: In 2013, a study showed low guideline adherence regarding chronic low back pain (CLBP) in physiotherapy students concerning activity and work recommendations (47% and 16%)1. The aim of this study is to investigate if the 2020' physiotherapy students'attitudes and beliefs regarding CLBP and osteoarthritis (OA) and the guideline adherence have changed since 2013, by using the same protocol. Methods: Physiotherapy students in their 2nd and 4th year of education from 6 Belgian and 2 Dutch institutions participated. The attitudes and beliefs regarding CLBP and OA were measured using the Pain attitudes and beliefs scale (BAPS), the Health Care Providers' Pain and Impairment Relationship Scale (HC-PAIRS) and a questionnaire regarding therapeutic exercise and knee OA. A clinical case vignette was used to measure the guideline adherence regarding CLBP. Results: In total, 2738 students participated, 1624 in 2013 and 1114 in 2020. Compared to 2013, students in 2020 scored lower on a biomedical orientation (p < 0.001) and higher on psychosocial orientations (p < 0.001) regarding CLBP and OA. Medium effect size (cohens'd = 0.548) was found on the psychosocial orientation of the PABS, other differences only had small effect sizes. In 2020, 54% provided clinical guidelines' consistent recommendations for activity and 28% for work, which significantly improved compared to 2013. Discussion: A positive shift occurred towards a more biopsychosocial approach between students of 2013 and 2020. However, the improved guideline adherence concerning activity and work recommendations remains low. Process evaluation: Additional clinical case vignette to measure clinical recommendations regarding OA would have strengthen this study. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic alliance (TA) is a necessity for optimal physiotherapy treatment for patients with musculoskeletal (MSK) pain1,2. Mutual understanding and open communication are important in building strong TA1,2. Building TA with patients from socio-cultural vulnerable groups seems to be difficult and might be related with higher risk on poor treatment outcomes3. Therefore, the aims of this study are to: (1) determine facilitators and barriers for building optimal TA with patients with MSK pain from socio-cultural vulnerable groups (2) develop and implement interventions to optimize TA. Methods: This participatory action research consists of multiple cycles of five phases in which researchers, clinicians and patients work closely together to investigate and optimize TA. Both observational research and semi-structured interviews will be conducted to gather data for reflection and deep understanding. Preliminary results will be used to collectively develop and implement interventions to optimize TA. This cycle of data collection and reflection will be repeated until optimal outcomes in TA are achieved from both therapist and patient perspective. Results: Diverse facilitators and barriers in TA are expected such as communication styles, language barriers, and expectations of treatment. Working together with patients and physiotherapists as co-researchers creates the ability to jointly investigate and optimize TA. Discussion: Since MSK pain is a frequent and debilitating health problem in patients from socio-cultural vulnerable groups, research into improving TA is important. By using participatory action research, knowledge about barriers and facilitators for TA can be obtained and changes in current physiotherapy practice may be facilitated. Process evaluation: Currently, the research design and practical preparations are being finalized. [ABSTRACT FROM AUTHOR]

Introduction: Up to >50% of individuals with symptomatic knee osteoarthritis (KOA) also report insomnia. Research suggests that the insomnia-pain link is bi-directional and complex with other factors like anxiety and mood being relevant. Network analysis allows to estimate these dynamic system interactions and to illustrate them graphically. This is an advantage over traditional statistical models (e.g. regression models) which investigate aspects of systems in isolation1. However, network analysis has not yet been utilized in the field of KOA and insomnia. Methods: We will use baseline data from a randomized controlled trial to estimate a cross-sectional network model connecting insomnia and pain in patients with KOA. The network structure will be estimated using Gaussian Graphical models with LASSO-regularization2. Established measures for sleep, pain, depression, anxiety, physical activity, pain catastrophizing and fatigue will be included. We will further analyse global network density and node centrality1. Results: The results will provide us a better understanding of how the network connecting pain and insomnia is built and which factors are most influential. Discussion: Our study will be the first that uses network analysis to understand the connection between KOA pain and insomnia. This will provide relevant clinical insights and interest other researchers in this exciting area of research. Process evaluation: Network analyses are new to me and there are not many examples in the field of chronic pain. It took me some time to understand the basics but the more I read the more excited I get about the opportunities these methods offer. [ABSTRACT FROM AUTHOR]

Introduction: Numerous scientific studies have established the necessity of a biopsychosocial (BPS) approach in the treatment of chronic pain, however, the implementation into clinical practice falls short. The aim of this study is to investigate the effectiveness of a BPS pain educational program for primary healthcare providers (PHCP) on changes in knowledge and attitude, and the guideline adherence. Methods: Within an implementation project of the Belgian Federal Government, a BPS pain educational program was developed based on recent scientific research, and barriers and facilitators formulated by an expert panel. 300 PHCP from various disciplines followed the course which contains two e-learning sessions and two one-day face-to-face trainings. Changes in knowledge and attitudes regarding chronic pain were measured using the KNowledge and Attitudes of Pain (KNAP). Guideline adherence was measured with two clinical case vignettes. Participants were measured pre-course, post-course and at a 6-month follow-up. The satisfaction of participants regarding the training and implementation into practice was measured during the course and at the follow-up. Results: A shift towards the biopsychosocial perspective that is in line with clinical guidelines is expected after completing the chronic pain course. Discussion: The pain course developed in the present study might increase the biopsychosocial perspective and guideline adherence of PHCP. Process evaluation: The selection of adequate evaluation tools to assess multidisciplinary groups was challenging. Furthermore, it remains to be established whether the improvements observed in knowledge and attitude questionnaires and the guideline adherence based on clinical vignettes reflect actual change in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Central sensitization is common in knee osteoarthritis patients (KOAP)1. Exercise therapy is suggested to be beneficial by activating endogenous analgesia2. Therefore, this systematic review aims to summarize the basal and/or acute effects of exercises on endogenous analgesia in KOAP. Methods: PubMed, Web of Science, and Embase were systematically searched. If possible, a meta-analysis was performed. Risk of bias was scored using the Cochrane ROB 2.0 or ROBINS-I and strength of evidence was assessed by the GRADE approach. Results: A total of 19 studies were included: 4 studies investigated pain thresholds after an acute bout of exercise; 15 articles focused on basal levels of endogenous analgesia (as measured by pain thresholds (n = 15), -facilitation (n = 3), and -inhibition (n = 2)). A meta-analysis combining 2 studies demonstrated that KOAP did not become more tolerant for pressure pain than healthy controls immediately after resistance training (p > 0.05). Besides that, one study with moderate quality of evidence showed that exercising KOAP had higher pain thresholds than non-exercising KOAP immediately after exercise (p < 0.05). A meta-analysis combining three studies showed that strength training of 6-12 weeks caused a significant increase in pain thresholds in KOAP compared to non-exercising KOAP (p < 0.05). Discussion: Very low quality of evidence proved that strength training of at least 6 weeks is effective in increasing pain thresholds in KOAP. Moderate quality of evidence demonstrated that an acute bout of exercise effectively increases pain thresholds in KOAP. Process evaluation: Literature about this topic is scarce, especially studies investigating pain facilitation (n = 3) and inhibition (n = 1). [ABSTRACT FROM AUTHOR]

Introduction: Chronic Whiplash Associated Disorders (CWAD) are characterized by long-lasting symptoms of neck pain occurring after an acceleration-deceleration injury. Central sensitization (CS) has been suggested as the possible underlying mechanism for these symptoms, and is characterized by changes in the central nervous system. Besides CS, psychological factors are believed to play an important role in the experience of (chronic) pain. Methods: 72 CWAD patients and 55 healthy controls underwent electrical stimuli-based quantitative sensory testing (QST). Detection and pain thresholds (EPT), temporal summation (TS) and conditioned pain modulation (CPM) were examined. Spearman correlations and linear mixed models analyses were performed to assess respectively the hypothesized associations with and group differences in QST. Results: The Pain Catastrophizing magnification subscale correlated with left wrist EPT (r = -0.332; p = 0.004), and the Pain Anxiety Symptom Scale-20 with left wrist (r = -0.325; p = 0.005) and ankle (r = -0.330; p = 0.005) EPT. TS at the ankle correlated with the CS Inventory (r = 0.303; p = 0.010), Short Form 36 pain subscale (r = -0.325; p = 0.005), and Illness Perception Questionnaire revised consequences subscale (r = 0.325; p = 0.005). EPTs of left (p = 0.011) and right wrist (p = 0.023) were lower in the CWAD group, but CPM and TS did not differ between groups. Discussion: QST outcomes relate to psychological constructs, rather than to self-reported pain intensity and distribution. Local hyperalgesia was found in CWAD patients, but no differences in endogenous pain facilitation nor inhibition. Process evaluation: Both CWAD patients reporting unilateral as bilateral neck pain were included, which complicated the interpretation of distal hyperalgesia. [ABSTRACT FROM AUTHOR]

Introduction: Research about perceived injustice (PI) in people with pain is expanding1. PI predicts adverse pain-related and disability outcomes2, and increases the risk of long-term opioid use potentially leading to side-effects3. Therefore, understanding PI in people with pain is necessary to target interventions and prevent pain chronicity. Methods: A systematic search was conducted. Two independent reviewers screened and evaluated the literature and extracted the data. Meta-analyses were performed for prevalence rates and factors associated with PI in people with pain. Results: Fifty-four studies were found eligible. Prevalence of PI ranged between 23-77% (I² = 99%). Significant associations were found with pain catastrophizing, posttraumatic stress, anger, anxiety, pain acceptance, depressive symptoms, kinesiophobia, academic functioning, disability, emotional functioning, pain interference, state anger, mental functioning, central sensitization, social functioning, physical functioning, pain perceptions, trait anger, pain intensity, and anger inhibition. Discussion: Prevalence was =33 in 75% of the studies. Considering PI in the treatment of people with pain is important due to its association with adverse pain, psychological, and quality of life characteristics. Process evaluation: This is the first systematic review estimating the prevalence and factors associated with PI. Methodologically, not all association measures (e.g., odds-ratios, beta-coefficients) could be included in the meta-analyses. Since we focussed on associations, we cannot draw any conclusions on causal interactions between PI and related factors in people with pain. [ABSTRACT FROM AUTHOR]

Introduction: Psychological factors and changes in sensory system play a role in low back pain (LBP). Psychological factors are examined by questionnaires and the sensory system by quantitative sensory testing (QST). Questionnaires Start Back screening Tool (SBT) and Central Sensitization Inventory (CSI) subgroup patients into risk respectively severity levels. The aim of this study was investigating the linear trend across the risk and severity levels based on the SBT and CSI for various psychological factors and sensitivity changes in the sensory system. Methods: Participants with LBP were recruited. Demographic information was taken, psychological questionnaires were filled in. Comprehensive QST was taken and linear contrast analysis was conducted in this cross-sectional study. Results: Psychological variables (e.g. kinesiophobia, catastrophizing) show significant positive linear trends across the risk levels of the SBT (p < 0.001) and severity levels of the CSI. Several QST-measurements show significant linear trends between the risk and severity levels based on the SBT (e.g. heat pain thresholdlow leg, p = 0.005) and CSI (e.g. pressure pain thresholdL4, p = 0.012). Discussion: Psychological factors increase as risk and severity levels increase. As the risk and/or severity levels increase some responsiveness of nociceptive neurons increased measured by pressure pain thresholds and heat pain thresholds. Temporal summation and conditioned pain modulation show no significant linear trends. Process evaluation: Recruiting people with LBP in primary care was challenging. Patients do not have often time to participate in research. It is helpful to actively approach different physiotherapists and to recruit participant in one's own working environment. [ABSTRACT FROM AUTHOR]

Introduction: Surgery, the cornerstone of most cancer treatments, is associated with considerable postoperative complications1. Adjusting patients' health behavior before surgery may have beneficial effects on postoperative outcomes. The objective of this trial is to investigate the feasibility and safety of, and patient-satisfaction and adherence with, patient-centered teleprehabilitation in patients undergoing breast cancer (BC) surgery. Methods: Women (n = 50) who will undergo breast surgery because of stage I-III BC are eligible. All participants will receive multimodal patient-centered teleprehabilitation comprising of motivational interviewing, education, exercise therapy, and stress management. Feasibility, participation rate, patient satisfaction, intervention safety, and treatment adherence will be monitored as primary outcomes. Fatigue, pain, quality of life (QoL), self-efficacy, and healthcare utilization will be assessed by self-reported questionnaires at baseline, 0-, 2-, and 6-months post-intervention. Results: Proof of concept for using telecommunication and exercise therapy in prehabilitation prior to BC surgery is available2,3. We expect the proposed intervention to be feasible and effective at reducing fatigue, pain, and healthcare use, and at improving treatment adherence, QoL, and self-efficacy. Discussion: Effective prehabilitation interventions can reduce the long-term symptoms that arise/persist beyond treatment completion, improving patients' QoL. By using telecommunication technologies, socio-economic barriers can be reduced, making care accessible to all. Process evaluation: With timely recruitment being the greatest challenge, a thorough mitigation strategy was put in place. Recruitment, drop-out, and loss-to-follow-up will constantly be monitored. Additional study centers confirmed their willingness to participate, and other study centers can easily be contacted through our collaboration with the Belgian Society of Medical Oncology. [ABSTRACT FROM AUTHOR]

Introduction: Insomnia is a common sleep disorder in people with knee osteoarthritis (KOA), adversely affecting daily function and general health1. It represents a barrier for effective conservative management. Clinical guidelines for KOA recommend integrating comorbidity-specific interventions as a part of patient-centred care2. However, insomnia is rarely addressed in the often joint-targeted KOA treatment. Methods: A two-arm randomized controlled trial (RCT) will be conducted on 128 patients with KOA and insomnia in a community setting. Subjects will randomly be allocated to the intervention group (cognitive behavioral therapy for insomnia (CBT-I) additional to best-practice KOA-care (education and exercise therapy)) or to the control group (best-practice KOA-care). The physiotherapist-led programme for both treatment arms will contain 18 sessions within 14 weeks, 30 minutes each. The primary outcome is pain intensity. Pain interference, sleep-related outcomes and physical activity/function are secondary outcomes. The tertiary outcomes are inflammation and healthcare utilisation. Blinded assessment will be conducted at baseline, post-intervention, and at 3 months, 6 months, and 12 months follow-up. Results: The results will give insights into the clinical and cost-effectiveness of CBT-I combined with best-practice physiotherapy. Discussion: This will be the first RCT integrating CBT-I in best-practice KOA-care in KOA patients with established insomnia whereby inflammation and sleep will be objectively assessed. This could help to improve the outcomes of a large proportion of KOA patients. Process evaluation: Being involved as a therapist in the trial and in the meanwhile developing my skills as a researcher, seems challenging. Is it all about getting the balance right? [ABSTRACT FROM AUTHOR]

Introduction: Numerous variables are associated with the physical activity level (PAL) and health-related quality of life (HRQOL) in various populations with chronic pain and fatigue. This study aims to identify transdiagnostic and disease-specific determinants of HRQOL and PAL in two distinct patient groups experiencing chronic pain and fatigue: patients with chronic fatigue syndrome (CFS) and multiple osteochondromas (MO). Methods: Data on sociodemographic, symptomatology, psychosocial variables, HRQOL and the PAL of patients with MO (n = 342) were collected at OLVG Amsterdam through a survey. The same data was collected at Vrije Universiteit Brussel of patients with CFS (n = 103). Determinants of HRQOL and PAL are explored with multiple linear regression models. Results: Preliminary results showed that both groups have a significantly lower HRQOL and PAL (p = 0.001) than the general population. PAL is expected to be positively associated with HRQOL in both groups. Pain and fatigue intensity and depression are hypothesized to be negatively associated with HRQOL and the PAL. The level of catastrophizing is lower in patients with MO; catastrophizing is hypothesized to be negatively associated with the PAL and HRQOL in patients with CFS, but not MO. Discussion: These results are expected to assist research and clinical practice in the development of evidence-based interventions aimed at maximizing HRQOL for patients with CFS and/or MO. Process evaluation: Explanatory variables are not measured with the same measurement instruments in both groups and require recoding. We need to compare associated variables between patient groups, dummy coding for the chronic condition seems the most appropriate procedure. [ABSTRACT FROM AUTHOR]

Introduction: Behavioural graded activity (BGA) has gained acceptance in chronic pain populations and is widely used in psychological informed practices (PIP)1. However, no review has been published about the effect of BGA in cancer populations. Therefore, the aim of this systematic review was to investigate the effectiveness of PIP with BGA compared to (1)waitlists (WLC), (2)other interventions (OI), (3)PIP-, or (4)BGA alone in cancer patients and survivors (CPaS). Methods: Three databases were screened for randomized controlled trials encompassing PIP with BGA in CPaS. Effect sizes of physical activity (PA), quality of life (QoL) and debilitating symptoms were inventoried. Subgroup analyses were undertaken to reduce heterogeneity (I2 > 50%). Results: Thirty-three studies were included, comprising 4330 participants. Significant effects of PIP+BGA comparing to WLC were found for anxiety (SMD:-1.29[-1.71;-0.86], I2 = 0%), fatigue (SMD:-0.86[-1.18;-0.54], I2 = 61%), depression (SMD:-0.79[-1.10;-0.48], I2 = 0%), functional impairment (SMD:-0.72[-0.95;-0.50], I2 = 0%), psychological distress (SMD:-0.58[-0.82;-0.34], I2 = 51%), PA (SMD:-0.58[-0.84;-0.32], I2 = 47% and SMD:-0.51[-0.90;-0.13], I2 = 0%), QoL (SMD:-0.38[-0.68;-0.09], I2 = 51%), social impairment (SMD:-0.33[-0.58;-0.08], I2 = 0%) and only the psychological distress (SMD:-0.89[-1.76;-0.02], I2 = 82%) remained significantly after one-to-three months. When comparing PIP+BGA to OI, significant effects were found for anxiety (SMD:-0.47[-0.88;-0.06], I2 = 83%), depression (SMD:-0.46[-0.84;-0.09], I2 = 82%), fatigue (SMD:-0.35[-0.51;-0.20], I2 = 48%), and PA (SMD:-0.26[-0.41;-0.11], I2 = 44%). One-to-three months post-intervention, effects for anxiety (SMD:-1.54[-2.88;-0.21], I2 = 87%), depression (SMD:-0.46[-0.84;-0.09], I2 = 82%) and fatigue (SMD:-0.34[-0.58;-0.10], I2 = 47%) remained significant. After four-to-six months significance only remained for anxiety (SMD:-0.14[-0.33;0.06], I2 = 0%). No significant effects were observed in the meta-analyses comparing PIP+BGA to BGA or PIP alone. Discussion: PIP with BGA is superior to non-behavioural interventions in improving anxiety, fatigue, depression, functional and social impairment, psychological distress, PA, and QoL in CPaS. Long-term improvements remained for anxiety, fatigue, depression and psychological distress. Process evaluation: Further research is needed on 'how' and 'when' BGA should be provided in cancer rehabilitation. [ABSTRACT FROM AUTHOR]

Introduction: Twenty-two percent of breast cancer survivors (BCSs) with pain are experiencing perceived injustice (PI)1. PI predicts adverse pain outcomes and opioid prescription due to increased pain behavior2. Educational interventions including reassurance and encouragement towards activity re-engagement are suggested to target PI3. Methods: Female BCSs (n = 156) experiencing pain+PI (=3 months post oncological treatment) are recruited. PI-targeted pain neuroscience education (PI-PNE) including motivational interviewing (rather biopsychosocially driven) is compared with biomedical pain education. The randomisation is done separately for each of the 6 treatment locations. Both interventions include an online session, information leaflet, and three one-to-one sessions. Online questionnaires assess pain, quality of life (QoL), PI, healthcare costs, sleep, fatigue, and cognitive-emotional factors at baseline and 0-, 6-, 12-, and 24-months post-intervention. A linear mixed model for repeated measures will evaluate whether the groups differ in terms of pain, PI, opioid use, and QoL after 12 months. Results: We expect that PI-PNE is superior to biomedical education at reducing pain, PI, and opioid use, and improving QoL in BCSs with pain and PI. Discussion: This is the first randomized controlled trial investigating the effectiveness of PI-PNE as a non-pharmacological strategy in BCSs with pain+PI. Process evaluation: Preparational work (e.g., ethical approval, interventions) is finalized. Recruitment started in April 2021 but is going slow due to COVID-19. Analyses are planned in 2023. [ABSTRACT FROM AUTHOR]

Introduction: Get Back is a further development of a prior person-centered prehabilitation project for lumbar fusion surgery (1). The program showed good effect on the patient's health related quality of life and had a high adherence rate and was found to be safe. Get Back aims to expand this program to include patients with lumbar spinal stenosis, who before surgery, have a worse starting position. This project aims to: (1) identify patients planned for surgery by screening for fear of movement and pain catastrophizing; (2) with person centered approach, via an e-health platform, support patients to challenge their fears of moving towards personal goals. Methods: The primary outcome is process feasibility conducted by the variables: recruitment rate, session compliance, and acceptability (2). Acceptability will more specifically be evaluated using questionnaires about the patient's and the physical therapist's satisfaction with the intervention. Preliminary treatment effects will be analyzed using validated self-report questionnaires, actigraph for measuring physical activity and functional capacity tests (3). Results: The hypothesis is that Get Back will: (1) be acceptable and increase patients' participation in their care. (2) increase patients' physical activity and health related quality of life compared to usual care. Discussion: The feasibility study will be followed by a multi-center randomized controlled trial. Process evaluation: The next step is to initiate a patient involvement process together with persons who have lived with lumbar spinal stenosis and undergone surgery to get input on the content and setup. [ABSTRACT FROM AUTHOR]

Introduction: Current perioperative education for patients undergoing lumbar surgery is only limited effective in preventing unfavorable outcome. Perioperative pain neuroscience education (PPNE) is a recently introduced intervention that aims to inform such patients about what to expect from their recovery, to improve maladaptive pain cognitions, and to reconceptualize pain. As such, this study aims to evaluate the effectiveness of PPNE on quality of life at 6 weeks post-surgery in at-risk patients undergoing surgery for lumbar radiculopathy. Methods: Following screening, 108 at-risk patients (i.e., having chronic pain = 6 months, and maladaptive degrees of kinesiophobia and pain catastrophizing) undergoing surgery for lumbar radiculopathy will be randomized into an experimental (PPNE) or control (perioperative biomedical education) group. Intervention includes a pre-and postoperative in-person session with a physiotherapist, and access to an educational web application. The primary outcome measure is quality of life which will be assessed at 1 week pre-surgery, and 6 weeks, 6 months and 1 year post-surgery. Results: The central hypothesis describes that due to the effect of PPNE these patients, despite their risk profile for unfavorable outcome, will have good surgical outcome with improvements in quality of life. Discussion: Findings will provide insight in the effectiveness of PPNE as a preventive measure for unfavorable surgical outcome and will be valuable for all clinicians working with such at-risk patients. Process evaluation: Though recruitment for this study has recently started, the process has been slow. As such, updated recruitment strategies are needed to help overcome current barriers. [ABSTRACT FROM AUTHOR]

Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease with unknown pathophysiology. Previous studies found lower salivary cortisol in patients with ME/CFS, which is referred to as hypocortisolism and is moreover associated with anxiety disorders. Therefore, we examined the relation between cortisol and anxiety specifically in patients with ME/CFS. Methods: Saliva of 28 patients with ME/CFS and 26 healthy controls (HCs) was collected twice. Cortisol levels were determined via liquid chromatography -mass spectrometry. Anxiety was assessed via the Beck Anxiety Inventory (BAI). Results: Cortisol levels were not significantly different between patients with ME/CFS (mean = 0.907 ng/ml; 95% C.I. 0.595 to 1.1219) and HCs (mean = 1.379 ng/ml; 95% C.I. 0.998 to 1.759; F = 3,702; p = 0.060). Patients with ME/CFS (mean = 39.582; 95% C.I. 37.320 to 41.844) had higher BAI scores than HCs (mean = 27.988; 95% C.I. 25.641 to 30.335; F = 49,984; p < 0.001). A weak, but significant, correlation was found between cortisol levels and anxiety on day 1 (r = -0.343; p = 0.03) and day 2 (r = -0.363; p = 0.018) in the entire group. Discussion: This study did not identify hypocortisolism in patients with ME/CFS. However, the negative correlation between anxiety and cortisol levels combined with the higher BAI scores in patients is consistent with literature, in which anxiety disorders are associated to hypocortisolism. Process evaluation: The study design was not ideal to determine differences in cortisol levels as this was not the main focus of the project. Cortisol levels were determined only once each day whereas, in ideal situations, daily cortisol output is determined via multiple measures per day because of the diurnal fluctuations in cortisol levels. [ABSTRACT FROM AUTHOR]

Introduction: Neck pain is the main consultation reason in primary care (PC) in Spain and with a prevalence of 8.4% in women and 3.2% in men1. Pain neuroscience communication (PNC) and motivational interviewing (MI) have been widely tested in chronic pain management and are successful for chronic pain management2. Objective: to evaluate the effectiveness of a complex intervention compared with routine PC physiotherapy to improve disability and intensity and severity of pain in patients with chronic neck pain (CNP). Methods: Randomized clinical trial. Subjects: Patients 18-65 years old with CNP referred from their physician. Sample: 142 patients. Intervention: PNC, MI and cognition targeted exercise (CTE). Control group: Standard PC health education program. Variables: Main: pain intensity. Secondary: pain severity, conditioned pain modulation, temporal summation, neck disability, fear/avoidance behaviours, kinesiophobia catastrophism, quality of life, and adherence. Follow-up: Baseline, 3, 6, 12 months. Results: We expect that patients with CNP in the intervention of PNC, MI and CTE will have a higher improvement in pain intensity, compared to the control group. Results: We expect that patients with CNP in the intervention of PNC, MI and CTE will have a higher improvement in pain intensity, compared to the control group. Process evaluation: We have recruited 32 clinicians from the PC, they will change their location so we will wait until that to start recruiting, also due to the pandemic, big group therapies are restricted so they will be reduced. Patients cannot be blind to the intervention, so appointments in different days to avoid communication will be made. [ABSTRACT FROM AUTHOR]

Introduction: The benefits of perioperative pain neuroscience education (PPNE) for people undergoing surgery for lumbar radiculopathy have recently been established. 1,2 However so far, not much is known about which factors influence PPNE's treatment success. Therefore, this study aims to assess the potential influence of preoperative pain intensity, pain cognitions and sensory function on the PPNE treatment effect for postoperative quality of life 1 year following surgery for lumbar radiculopathy. Methods: This study is a secondary analysis of a randomized controlled trial in which 120 patients were randomized to receive either PPNE or perioperative biomedical education (PBE).3 Quality of life was assessed using the Short Form 36-item Health Survey (SF-36) at baseline (1 week pre-surgery), and 6 weeks, 6 months and 1 year post-surgery. Linear mixed models will be built for the SF-36 Physical component, SF-36 Mental component, and SF-6D utility scores using the following independent variables: treatment (PPNE versus PBE), time, and baseline scores for back pain intensity, leg pain intensity, pain catastrophizing, kinesiophobia, hypervigilance, and measures of quantitative sensory testing (i.e., electrical pain threshold, temporal summation, and conditioned pain modulation). Results: It is hypothesized that patients who report unfavorable scores for these preoperative factors will show a larger treatment effect of PPNE on postoperative quality of life. Discussion: Findings will provide novel insight into the potential moderating effect of preoperative factors on treatment outcome following PPNE in people undergoing surgery for lumbar radiculopathy. Process evaluation: Analysis for this study is underway and results are expected in Spring 2022. [ABSTRACT FROM AUTHOR]

Introduction: Whiplash injuries typically occur from a motor vehicle collision and lead to chronic whiplash associated disorders (CWAD) in 20-50% of cases. Changes in neurotransmission, metabolism and networks seem to play a role in the pathogenic mechanisms of CWAD. Methods: This case-control study (CWAD patients/healthy controls (HC):50/50), investigated ankle and wrist electrical pain thresholds (EPT) and the amplitude and latency of event-related potentials (ERPs) resulting from 20 electrical stimuli at the intensity of 1,4xEPT. Linear mixed effect models were applied to detect group differences in EPTs and ERP characteristics. Correlations between ERP characteristics, EPT, self-reported pain, disability, pain catastrophizing and symptoms of central sensitisation (CS) were investigated. Results: In CWAD patients, left wrist P3 latency (t = -2.283; p = 0.023) was prolonged, and their ankle EPT correlated with ankle P1 (ρs = 0.293; p = 0.044) and P3 amplitude (ρs = 0.306; p = 0.033), and left wrist P3 amplitude (ρs = 0.343; p = 0.017). Symptoms of CS correlated with right wrist P3 amplitude (ρs = 0.308; p = 0.030) and latency (ρs = -0.341; p = 0.015), and the worst pain during the week before the assessment correlated with left wrist P1 latency (ρs = 0.319; p = 0.029). Discussion: CWAD patients did not show signs of hypersensitivity, but their ERP characteristics seemed to be related to the intensity of the stimulus, self-reported symptoms of CS, and worst pain during the week before the assessment. Process evaluation: Self-reported disability had changed between time of inclusion and baseline assessment, resulting in the inclusion of 8 CWAD patients with low disability at baseline. [ABSTRACT FROM AUTHOR]

Introduction: Many patients with chronic widespread pain (CWP) experience stress intolerance -an exacerbation of symptoms in response to stress. The effect of stress on pain depends on the magnitude of the (autonomic) stress response, which is variable between and even within subjects. This project aims to explain the variability in the autonomic stress response and link it to stress intolerance by investigating the effect of epigenetics on catecholamine expression (messengers of the autonomic nervous system (ANS)) and ANS activity in general. Methods: Patients with CWP (n = 44) and age-and BMI-matched healthy controls (n = 44) are enrolled in a randomised cross-over study. In the experimental procedure, mental stress is induced via the Montreal Imaging Stress Test. The control procedure consists of relaxation breathing. The following outcomes are assessed before, during and after each procedure: (1) biological: DNA methylation of genes encoding for catecholamine-degrading enzymes, enzymatic activity of those enzymes and catecholamine expression; (2) neurophysiological: heart rate variability and blood pressure; (3) clinical: pain thresholds and symptom severity. Symptom severity will also be monitored online one day and seven days after their visits. Results: We expect that higher levels of DNA methylation affect the enzymatic activity of catecholamine-degrading enzymes, in turn leading to dysregulated ANS activity and stress intolerance in patients with CWP. Discussion: This design will allow us to provide causal statements about the role of epigenetics in stress intolerance. Process evaluation: The project will be initiated in May 2022. All laboratory methods will be validated and optimised before the samples of this project will be analysed. [ABSTRACT FROM AUTHOR]

Background: Up to 30% of people infected with SARS-CoV-2 report disabling symptoms 2 years after the infection. Over 100 persistent symptoms have been associated with Post-Acute COVID-19 Symptoms (PACS) and/or long-COVID, showing a significant clinical heterogeneity. To develop effective, patient-targeted treatment, a better understanding of underlying mechanisms is needed. Epigenetics has helped elucidating the pathophysiology of several health conditions and it might help unravelling inter-individual differences in patients with PACS and long-COVID. As accumulating research is exploring epigenetic mechanisms in PACS and long-COVID, we systematically summarized the available literature on the topic., Methods: We interrogated five databases (Medline, Embase, Web of Science, Scopus and medXriv/bioXriv) and followed PRISMA and SWiM guidelines to report our results., Results: Eight studies were included in our review. Six studies explored DNA methylation in PACS and/or long-COVID, while two studies explored miRNA expression in long-COVID associated with lung complications. Sample sizes were mostly small and study quality was low or fair. The main limitation of the included studies was a poor characterization of the patient population that made a homogeneous synthesis of the literature challenging. However, studies on DNA methylation showed that mechanisms related to the immune and the autonomic nervous system, and cell metabolism might be implicated in the pathophysiology of PACS and long-COVID., Conclusion: Epigenetic changes might help elucidating PACS and long-COVID underlying mechanisms, aid subgrouping, and point towards tailored treatments. Preliminary evidence is promising but scarce. Biological and epigenetic research on long-COVID will benefit millions of people suffering from long-COVID and has the potential to be transferable and benefit other conditions as well, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We urge future research to employ longitudinal designs and provide a better characterization of included patients.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms., Methods: A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software., Results: This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31-.67]; Z = 5.29, p < .01) and β1 adrenergic receptor expression (SMD = .79 [.06-1.52]; Z = 2.13; p = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18-.97]; Z = 2.85, p < .01), β2 AR (SMD = .41 [.02-.81]; Z = 2.04; p = .04) and COMT (SMD = .42 [.03-.81]; Z = 2.11; p = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [-.47 to -.70]; Z = 2.10; p = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = -.79 [-1.27 to -.30]; Z = -3.14; p < .01)., Conclusion: This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background/Objectives : To investigate if intra-articular biomarkers relate to peripheral and central sensitization in patients with late-stage knee osteoarthritis (KOA). Methods : A total of 17 (6M, 11F) patients (aged 69 ± 10 years) were assessed for peripheral (pressure pain thresholds (PPT)) and central (temporal summation (TS) and conditioned pain modulation (CPM)) sensitization the day before total knee arthroplasty. Synovial fluid was collected during surgery and assayed for IL-6, IL-8, IL-10, TNF-α, CXCL-10, BDNF, NGF, CCL2, CCL5, VEGF, IL-1RI, MMP-1, MMP-7, IL-1β, and CXCL-9. Associations of biomarkers and their combinations reflecting chronic (CXCL-9) and acute ((CCL2×CXCL-10)/IL-10)) inflammation, cartilage degeneration (MMP-1×MMP-7), and neurotrophy (NGF×BDNF) with PPT, TS, and CPM were analyzed by bivariate correlations and by multiple linear regression analyses corrected for BMI, sex, and age. Results : The medial joint line and the superior medial joint region showed the lowest PPT. Higher acute inflammation related significantly to worse pressure tenderness at the superior medial joint region (R 2 = 0.642; p = 0.010). Cartilage degeneration and chronic inflammation were associated with both absolute (R 2 = 0.827; p = 0.001) and relative CPM (R 2 = 0.882; p < 0.001). Acute inflammation and neurotrophy were related to relative TS at the m. tibialis anterior (R 2 = 0.728; p = 0.02). Conclusions : This study demonstrates that increased levels of intra-articular biomarkers of acute inflammation are related to peripheral sensitization and that biomarkers of cartilage degeneration and chronic inflammation are associated with central sensitization. These results may be a stepping-stone toward a better understanding of the working mechanism of peripheral and central sensitization in KOA pain and the development of more targeted therapeutic interventions.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: Pain is a prevalent side-effect seen in breast cancer survivors (BCS). Psychological factors are known role-players in pain mechanisms. Both pain and psychological factors contribute to or interact with healthcare use (HCU). However, the association between psychological factors and HCU has never been investigated in BCS with pain, which is aimed in this study., Methods: Belgian BCS with pain (n = 122) were assessed by the Medical Consumption Questionnaire, Injustice Experienced Questionnaire, Pain Catastrophizing Scale, Pain Vigilance and Awareness Questionnaire, Brief Illness Perceptions Questionnaire, and the Depression, Anxiety and Stress Scale. Associations were analyzed using logistic and Poisson regressions., Results: Opioid use was related to more catastrophizing and less psychological distress. Psychotropic drug was related to more psychological distress. Endocrine therapy related to less vigilance and awareness. Psychological distress related to all types of healthcare provider (HCP), with psychological distress negatively related to physiotherapy, psychology, and other primary HCP visits, and positively with visiting a general practitioner and secondary HCP. Catastrophizing related to more visiting behavior in primary HCP, except to a general practitioner. Perceived injustice related to more general practitioner and other primary HCP visits, but to fewer psychology visits. Illness perceptions are only related to visiting other primary HCP. Vigilance and awareness was related to more psychologist and secondary HCP visits., Conclusion: Our findings underscore the complex interplay between HCU and psychological factors in BCS with pain. Psychological distress was overall the most important psychological factor related to HCU, whether catastrophizing and perceived injustice were the most relevant related to HCP visits., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Though perioperative pain neuroscience education (PPNE) positively influences patients' surgical outcomes, little is known about the mechanisms behind this treatment's success. Therefore, this study aims to evaluate the potential mediating role of pain cognitions and pain sensitivity in the treatment effect of PPNE on postoperative quality of life in people undergoing surgery for lumbar radiculopathy. This secondary analysis uses data from 120 participants of a randomized controlled trial who were randomized to receive either PPNE or perioperative biomedical education before undergoing surgery for lumbar radiculopathy. Quality of life was assessed 1-year postsurgery using the short form 36-item health survey (SF36) physical and mental component scores. Potential mediators included pain cognitions (ie, kinesiophobia, pain catastrophizing, and hypervigilance) and pain sensitivity (ie, endogenous nociceptive modulation), assessed 6 weeks postsurgery. Mediation models were constructed using structural equation modeling, and 95% confidence intervals (CIs) were calculated using 10,000 bootstrap samples. Analyses show a significant total effect for PPNE (estimate = .464, 95% CI [.105, .825]) and a significant indirect effect via pain catastrophizing on the SF36 physical component (estimate = .124, 95% CI [.001, .293]). No mediating effect was found through the remaining pain cognitions or pain sensitivity measures. Also, no potential mediators were identified for the treatment effect of PPNE on the SF36 mental component. Our findings suggest that pain catastrophizing mediates the treatment effect of PPNE on physical health-related quality of life in people undergoing surgery for lumbar radiculopathy. PERSPECTIVE: This secondary analysis identified pain catastrophizing as a mediator for PPNE in people undergoing surgery for lumbar radiculopathy. More so, its findings indicate that this educational intervention can enhance the postoperative physical health-related quality of life of these patients by addressing their catastrophizing thoughts. TRIAL REGISTRATION: Clinicaltrials.gov (NCT02630732)., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)