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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: 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: 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: 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: 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: 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: 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.)

Purpose: This systematic review and meta-analysis aimed to determine the effectiveness of psychologically informed practice (PIP) with behavioural graded activity (BGA) compared to (1) waitlist controls (WLC), (2) other interventions (OI), (3) PIP alone or (4) BGA alone in cancer patients and survivors (CPaS)., Methods: PubMed, Web of Science and Embase were screened for randomised controlled trials encompassing BGA + PIP in CPaS. Effect sizes were inventoried for outcomes regarding physical activity (PA), quality of life (QoL) and debilitating symptoms (DS), which were assessed at four time points: post-intervention (PI), follow-up F1 (1 to 3 months), F2 (4 to 6 months) and F3 (> 6 months). The quality of the evidence was classified by the GRADE approach., Results: Thirty-three studies were found eligible, comprising 4330 participants. Significant effects with low heterogeneity of PIP + BGA comparing to WLC were found for anxiety (SMD - 1.29 [-1.71; - 0.86]), depression (SMD - 0.79 [- 1.10; - 0.48]), functional impairment (SMD - 0.72 [- 0.95; - 0.50]), PA (self-reported: (SMD - 0.58 [- 0.84; - 0.32]) and objectively measured: (SMD - 0.51 [- 0.90; - 0.13])) and social impairment (SMD - 0.33 [- 0.58; - 0.08]). When comparing PIP + BGA to OI, fatigue (SMD - 0.35 [- 0.51; - 0.20]) and PA (SMD - 0.26 [- 0.41; - 0.11]) at PI, and fatigue (SMD - 0.34 [- 0.58; - 0.10]) at F1 were found significant with low heterogeneity. No significant effects were observed in the meta-analyses of studies comparing PIP + BGA to BGA or PIP alone., Conclusions: PIP with BGA has a favourable effect on DS, PA and QoL in CPaS when compared to non-behavioural interventions such as WLC, usual care and education. However, further research is needed on 'how' and 'when' PIP + BGA should be provided in cancer rehabilitation., Implications for Cancer Survivors: PIP + BGA has the potential to facilitate CPaS to reach the recommended amount of PA and reduce DS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The primary aim of this cross-sectional study is to examine the prevalence of pain phenotypes in breast cancer survivors (BCS). A secondary aim entails examining whether health related quality of life differs between the main pain phenotypes in BCS., Methods: BCS who experienced chronic pain were asked to complete the numeric pain rating scale for pain, Margolis pain diagram, and short form 36 (SF-36). Following administration of questionnaires and quantitative sensory examinations were applied. To determine the prevalence of the predominant type of pain, a recently proposed classification system by the Cancer Pain Phenotyping (CANPPHE) Network was used., Results: Of the 86 female participants, 19 (22.09%) had dominant neuropathic pain, 18 (20.93%) had dominant nociceptive pain and 14 (16.28%) had dominant nociplastic pain. 35 participants (40.70%) were classified as having mixed pain. One-way ANOVA revealed a significant difference between the four pain groups for the SF-36 general health (F = 3.205, p = 0.027), social functioning (F = 4.093, p = 0.009), and pain (F = 3.603, p = 0.017) subscale scores., Conclusion: This study found that pain in BCS was mostly of mixed phenotype, followed by predominantly neuropathic and nociplastic pain. Furthermore, it was found that, compared to BCS with predominant neuropathic and nociceptive pain, BCS with predominant nociplastic pain have lower health related quality of life in the areas of bodily pain and social functioning., (© 2024. The Author(s).)

Introduction: Current treatments for pain in breast cancer survivors (BCSs) are mostly biomedically focused rather than biopsychosocially driven. However, 22% of BCSs with pain are experiencing perceived injustice, which is a known predictor for adverse pain outcomes and opioid prescription due to increased maladaptive pain behaviour. Educational interventions such as pain neuroscience education (PNE) are suggested to target perceived injustice. In addition, motivational interviewing can be an effective behavioural change technique. This trial aims to examine whether perceived injustice-targeted PNE with the integration of motivational interviewing is superior to biomedically focused pain education in reducing pain after 12 months in BCS with perceived injustice and pain. In addition, improvements in quality of life, perceived injustice and opioid use are evaluated, and a cost-effectiveness analysis will finally result in a recommendation concerning the use of perceived injustice-targeted PNE in BCSs with perceived injustice and pain., Methods and Analysis: This two-arm multicentre randomised controlled trial will recruit female BCS (n=156) with pain and perceived injustice. Participants will be randomly assigned to perceived injustice-targeted PNE or biomedically focused pain education in each centre. Both interventions include an online session, an information leaflet and three one-to-one sessions. The primary outcome (pain), secondary outcomes (quality of life, perceived injustice and outcomes for cost-effectiveness analysis) and explanatory outcomes (pain phenotyping, sleep, fatigue and cognitive-emotional factors) will be assessed at baseline and at 0, 6, 12 and 24 months postintervention using self-reported questionnaires online. Treatment effects over time will be evaluated using linear mixed model analyses. Additionally, a cost-utility analysis will be done from a healthcare payer and societal perspective., Ethics and Dissemination: The ethical agreement was obtained from the Main Ethics Committee (B.U.N.1432020000068) at the University Hospital Brussels and all other participating hospitals. Study results will be disseminated through presentations, conferences, social media, press and journals., Trial Registration Number: NCT04730154., Competing Interests: Competing interests: JN and the Vrije Universiteit Brussel received lecturing/teaching fees from various professional associations and educational organisations. JN, PVW, LL and EH authored a book on PNE, but the royalties are collected by the Vrije Universiteit Brussel and not them personally., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Muscle strengthening training (MST) and behavioural graded activity (BGA) show comparable effects on knee osteoarthritic (KOA) pain, but the mechanisms of action remain unclear. Both exercise-induced anti-inflammation and central sensitisation are promising pathways for pain relief in response to exercise therapy in patients with KOA: MST has the potential to decrease inflammation and BGA has the potential to decrease central sensitisation. Hence, this study aims to examine inflammation and central sensitisation as mediators for the effect of MST and/or BGA on pain in patients with KOA., Methods and Analysis: The Knee OsteoArthritis PAIN trial started on 10 January 2020 (anticipated end: April 2024). The three-arm clinical trial aims to recruit 90 KOA patients who will be randomly allocated to 12 weeks of (1) MST, (2) BGA or (3) care as usual. Assessments will be performed at baseline, 13 and 52 weeks after finishing the intervention. Outcomes, including pain (Knee injury and Osteoarthritis Outcome Score), were chosen in line with the OARSI recommendations for clinical trials of rehabilitation interventions for OA and the IMMPACT/OMERACT recommendations for the assessment of physical function in chronic pain clinical trials. Inflammation as well as features of central sensitisation (including conditioned pain modulation, offset analgesia, temporal summation of pain and event-related potentials following electrical stimulation), will be considered as treatment mediators. A multiple mediators model will be estimated with a path-analysis using structural equation models. In July 2023, all 90 KOA patients have been included and 42 participants already finished the study., Ethics and Dissemination: This study obtained ethics approval (B.U.N. 143201941843). Unravelling the mechanisms of action of exercise therapy in KOA will not only be extremely valuable for researchers, but also for exercise immunology and pain scientists and clinicians., Trial Registration Number: NCT04362618., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Fatigue and pain are the most common side effects impacting quality of life (QoL) in cancer survivors. Recent insights have shown that perceived injustice (PI) can play a substantial role in these side effects, but research on cancer survivors is scarce. Furthermore, guidelines for recognizing clinically relevant levels of PI in cancer survivors are missing. The aims of this study are to provide a clinically relevant cut-off for PI and to explore relationships between personal characteristics, symptoms, and QoL with PI. This multicenter, cross-sectional study uses the Injustice Experience Questionnaire (IEQ), Numeric Pain Rating Scale (NPRS), Patient-Specific Complaints (PSC), Multidimensional Fatigue Index (MFI), and European Organization for Research and Treatment of Cancer QoL Questionnaire-C30 (EORTC-QLQ-C30). A clinical cut-off for PI was identified based on the 75th percentile of IEQ scores. Univariate and multivariate regressions explored the relationship between PI and personal characteristics (sex, age, cancer type, treatment type), symptoms (pain intensity, fatigue), and QoL (daily activity complaints, cancer-related QoL). Cancer survivors (n = 121) were included, and a cut-off of 20 was identified. Significant indirect associations were found between chemotherapy, NPRS, PSC, MFI, and EORTC-QLQ-C30 with PI. In the multivariate model, only MFI (B = 0.205; 95% CI: 0.125-0.018) and age (B = 0.086; 95% CI: -0.191-0.285) maintained a significant association with PI.

Pain after cancer remains underestimated and undertreated. Precision medicine is a recent concept that refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics. Applying this to pain after cancer, the ability to classify post-cancer pain into the three major pain phenotypes (i.e. nociceptive, neuropathic, and nociplastic pain) and tailor pain treatment accordingly, is an emerging issue. This is especially relevant because available evidence suggests that nociplastic pain is present in an important subgroup of those patients experiencing post-cancer pain. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system for nociplastic pain account for the need to identify and correctly classify patients according to the pain phenotype early in their treatment. These criteria are an important step towards precision pain medicine with great potential for the field of clinical oncology. Within this framework, the Cancer Pain Phenotyping (CANPPHE) Network, an international and interdisciplinary group of oncology clinicians and researchers from seven countries, applied the 2021 IASP clinical criteria for nociplastic pain to the growing population of those experiencing post-cancer pain. A manual is provided to allow clinicians to differentiate between predominant nociceptive, neuropathic, or nociplastic pain after cancer. A seven-step diagnostic approach is presented and illustrated using cases to enhance understanding and encourage effective implementation of this approach in clinical practice., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Perceived injustice (PI) is a multidimensional appraisal cognition comprising the severity of loss consequent to injury, blame, a sense of unfairness, and/or irreparability of loss. PI gained increasing interest in pain research since it potentially contributes to the experience and burden of (chronic) pain., Objectives: This systematic review aimed to determine the prevalence of PI and factors associated with PI in people with pain., Study Design: Systematic review with meta-analysis., Methods: Web of Science, PubMed, and Embase were screened for cross-sectional or cohort studies encompassing human patients who were diagnosed with a condition causing pain and reported prevalence rates for PI and/or associations between a factor and PI. Meta-analyses were carried out, and subgroup analyses were undertaken based on the methodological quality of the studies, the type of pain population, and whether the outcome measure was valid or not in case of heterogeneity (P < 0.05)., Results: Fifty-four studies were found eligible. The prevalence of PI ranged from 23% to 77% (I2 = 99%, P < 0.001). Association with PI, assessed using the Injustice Experienced Questionnaire, were found with pain catastrophizing (pooled Pearson's r [rp] = 0.66 [0.64, 0.69], P < 0.00001), posttraumatic stress (rp = 0.63 [0.59, 0.67], P < 0.00001), anger (rp = 0.59 [0.49, 0.67], P < 0.00001), anxiety (rp = 0.59 [0.52, 0.64], P < 0.00001), pain acceptance (rp = -0.59 [-0.66, -0.49], P < 0.00001), depressive symptoms (rp = 0.57 [0.52, 0.60], P < 0.00001), kinesiophobia (rp = 0.57 [0.50, 0.64], P < 0.00001), academic functioning (rp = -0.54 [-0.65, -0.41], P < 0.00001), disability (rp = 0.53 [0.47, 0.59], P < 0.00001), emotional functioning (rp = -0.52 [-0.64, -0.39], P < 0.00001), pain interference (rp = 0.49 [0.35, 0.60], P < 0.00001), state anger (rp = 0.48 [0.41, 0.54], P < 0.00001), mental functioning (rp = -0.48 [-0.57, -0.38], P < 0.00001), symptoms of central sensitization (rp = 0.47 [0.39, 0.55], P < 0.00001), social functioning (rp = -0.47 [-0.60, -0.31], P < 0.00001), and physical functioning (rp = -0.43 [-0.53, -0.33], P < 0.00001), pain perceptions (rp = 0.40 [0.40, 0.64], P < 0.00001), trait anger (rp = 0.40 [0.29, 0.49], P < 0.00001), pain intensity (rp = 0.37 [0.33, 0.42], P < 0.00001), and anger inhibition (rp = 0.35 [0.26, 0.43], P < 0.00001)., Limitations: Some articles had to be excluded due to the absence of a full-text version. The findings can largely be applied to developed and high-income countries, but further research is needed in developing countries. Also, no validated cutoff values were available for the National Institutes of Health to determine the methodological quality of the included studies. Lastly, high heterogeneity was observed in many of the performed analyses. However, this was addressed by performing subgroup analyses, which could decrease heterogeneity in some cases., Conclusions: The prevalence of PI was >= 33% in 75% of the studies indicating that PI is important to consider in people with pain. There is evidence for the association of PI with psychological, pain, and quality of life characteristics in people with pain. The associations of PI with personal, injury, and recovery characteristics were overall not significant or negligible.

Human spaceflight is associated with several health-related issues as a result of long-term exposure to microgravity, ionizing radiation, and higher levels of psychological stress. Frequent reported skin problems in space include rashes, itches, and a delayed wound healing. Access to space is restricted by financial and logistical issues; as a consequence, experimental sample sizes are often small, which limits the generalization of the results. Earth-based simulation models can be used to investigate cellular responses as a result of exposure to certain spaceflight stressors. Here, we describe the development of an in vitro model of the simulated spaceflight environment, which we used to investigate the combined effect of simulated microgravity using the random positioning machine (RPM), ionizing radiation, and stress hormones on the wound-healing capacity of human dermal fibroblasts. Fibroblasts were exposed to cortisol, after which they were irradiated with different radiation qualities (including X-rays, protons, carbon ions, and iron ions) followed by exposure to simulated microgravity using a random positioning machine (RPM). Data related to the inflammatory, proliferation, and remodeling phase of wound healing has been collected. Results show that spaceflight stressors can interfere with the wound healing process at any phase. Moreover, several interactions between the different spaceflight stressors were found. This highlights the complexity that needs to be taken into account when studying the effect of spaceflight stressors on certain biological processes and for the aim of countermeasures development.

Background: In the pathogenesis of knee osteoarthritis (KOA), inflammatory mediators play an important role. However, the precise underlying mechanism by which regular exercise therapy (ET) exert effects on the immune system in KOA patients is unknown., Objectives: The aim of this systematic review was to investigate the basal and acute effects of ET on inflammatory biomarkers and brain derived neurotrophic factor (BDNF) in KOA patients., Methods: PubMed, Web Of Science and PEDro were systematically searched for appropriate studies. If possible, a meta-analysis was performed or an approximation of the effect size (ES) was calculated. Risk of bias was scored using the Cochrane ROB 2.0 or ROBINS-tools., Results: Twenty-one studies involving 1374 participants were included. Fifteen articles focused on basal exercise effects, four on acute effects, and two on both. Biomarker analysis (n=18) was performed in synovial fluid (n=4) or serum/plasma (n=17). A meta-analysis demonstrated that basal CRP was reduced in KOA patients 6-18 weeks weeks after ET (MD: -0.17;95%CI[-0.31;-0.03]), while IL-6 (MD: 0.21;95%CI[-0.44;0.85]), and TNF-α (MD: -0.57;95%CI[-1.47;0.32]), levels did not significantly change. Also, sTNFR1/2 did not change significantly after ET. For other biomarkers, insufficient data were available to perform a meta-analysis. Nevertheless, a low degree of evidence was found for a decrease in IL-6 (ES:-0.596 & -0.259 & -0.513), an increase in sTNFR1 (ES:2.325), a decrease in sTNFR2 (ES:-0.997) and an increase in BDNF (ES:1.412). Locally, intra-articular IL-10 (ES:9.163) increased, and IL1β (ES:-6.199) and TNF-α decreased (ES:-2.322) after ET. An acute exercise session elicited a myokine response (ES IL-6:0.314), and an increase in BDNF (no ES-data). No inflammatory effect (ES CRP:0.052; ES TNF-α:-0.019 & 0.081) following an acute bout of training was found. However, a single bout of exercise elicited a decrease in intra-articular IL-10 (no ES-data)., Conclusion: ET can induce circulatory and intra-articular anti-inflammatory effects in patients with KOA. The antiinflammatory properties have important implications for informing these patients and clinicians about the underlying effects of ET., (Copyright © 2023 International Society of Exercise and Immunology. All rights reserved.)

Background: For patients with therapy-refractory persistent spinal pain syndrome type II (PSPS-T2), spinal cord stimulation (SCS) may serve as an effective minimally invasive treatment. Despite the evidence that SCS can improve return to work (RTW), only 9.5 to 14% of patients implanted with SCS are effectively capable of returning to work. Thus, it seems that current post-operative interventions are not effective for achieving RTW after SCS implantation in clinical practice. The current objective is to examine whether a personalised biopsychosocial rehabilitation programme specifically targeting RTW alters the work ability in PSPS-T2 patients after SCS implantation compared to usual care., Methods: A two-arm, parallel-group multicentre randomised controlled trial will be conducted including 112 patients who will be randomised (1:1) to either (a) a personalised biopsychosocial RTW rehabilitation programme of 14 weeks or (b) a usual care arm, both with a follow-up period until 12 months after the intervention. The primary outcome is work ability. The secondary outcomes are work status and participation, pain intensity, health-related quality of life, physical activity and functional disability, functional capacities, sleep quality, kinesiophobia, self-management, anxiety, depression and healthcare expenditure., Discussion: Within the OPERA project, we propose a multidisciplinary personalised biopsychosocial rehabilitation programme specifically targeting RTW for patients implanted with SCS, to tackle the high socio-economic burden of patients that are not re-entering the labour market. The awareness is growing that the burden of PSPS-T2 on our society is expected to increase over time due to the annual increase of spinal surgeries. However, innovative and methodologically rigorous trials exploring the potential to decrease the socio-economic burden when patients initiate a trajectory with SCS are essentially lacking., Trial Registration: ClinicalTrials.gov NCT05269212. Registered on 7 March 2022., (© 2022. The Author(s).)

This review discusses chronic pain, multiple modifiable lifestyle factors, such as stress, insomnia, diet, obesity, smoking, alcohol consumption and physical activity, and the relationship between these lifestyle factors and pain after cancer. Chronic pain is known to be a common consequence of cancer treatments, which considerably impacts cancer survivors' quality of life when it remains untreated. Improvements in lifestyle behaviour are known to reduce mortality, comorbid conditions (i.e., cardiovascular diseases, other cancer, and recurrence) and cancer-related side-effects (i.e., fatigue and psychological issues). An inadequate stress response plays an important role in dysregulating the body's autonomic, endocrine, and immune responses, creating a problematic back loop with pain. Next, given the high vulnerability of cancer survivors to insomnia, addressing and treating those sleep problems should be another target in pain management due to its capacity to increase hyperalgesia. Furthermore, adherence to a healthy diet holds great anti-inflammatory potential for relieving pain after cancer. Additionally, a healthy diet might go hand in hand with weight reduction in the case of obesity. Consuming alcohol and smoking have an acute analgesic effect in the short-term, with evidence lacking in the long-term. However, this acute effect is outweighed by other harms on cancer survivors' general health. Last, informing patients about the benefits of an active lifestyle and reducing a sedentary lifestyle after cancer treatment must be emphasised when considering the proven benefits of physical activity in this population. A multimodal approach addressing all relevant lifestyle factors together seems appropriate for managing comorbid conditions, side-effects, and chronic pain after cancer. Further research is needed to evaluate whether modifiable lifestyle factors have a beneficial influence on chronic pain among cancer survivors.

Background: 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., Objective: Investigating the relationships between self-reported pain, disability, quality of life, psychological factors, and symptoms of CS; and electrical-based quantitative sensory testing (QST) outcomes in CWAD patients. Secondly, to investigate the differences in QST between CWAD patients and pain-free controls., Methods: Seventy-two individuals with CWAD and 55 pain-free controls underwent electrical stimuli-based QST. Detection and pain thresholds (EPT), temporal summation (TS), and conditioned pain modulation were examined. Spearman correlation and linear mixed models analyses were performed to assess, respectively, the hypothesized associations and group differences in QST., Results: The Pain Catastrophizing magnification subscale correlated with the left wrist EPT (r=-0.332; P=0.004), and the Pain Anxiety Symptom Scale-20 with the 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 left (P=0.011) and right wrist (P=0.023) were lower in the CWAD group, but conditioned pain modulation and TS did not differ between groups., Conclusion: QST outcomes relate to psychological constructs, rather than to self-reported pain intensity and distribution. Local hyperalgesia was found in individuals with CWAD, but no differences in endogenous pain facilitation nor inhibition., Competing Interests: D.L. was funded by the Bijzonder Onderzoeksfonds (BOF) Gent, Belgium. I.C., W.W., and A.M.: were funded by the Flemish Research Institution (FWO), Brussels, Belgium. The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)