PURPOSE:This paper aims to understand the distinctive biopsychosocial aspects and patient perspectives on chronic low back pain in Lebanon, an Arab country with a unique and rich cultural heritage. METHOD:Qualitative, semi-structured interviews with 12 Lebanese patients purposefully sampled from various governorates. The interviews included participants from different geographic areas and religions. The data underwent analysis through an inductive thematic approach guided by a bounded relativist ontology, a subjectivist epistemology, and a descriptive phenomenological framework. The coding process was managed by computer-assisted qualitative data analysis software (QSR NVivo version 12.0). RESULTS:The researchers identified and constructed two themes: (1) Chronic low back pain: understanding the impact, coping strategies, and communication patterns in lived experiences within the Lebanese context. This theme sheds light on the complexities of pain management and societal influences in Lebanon. (2) Explanatory model of patients living with chronic low back pain in Lebanon. This theme allowed an exploration of the multifaceted narratives of chronic low back pain. CONCLUSION:This study found that Lebanese individuals attribute chronic low back pain to biomedical factors despite some recognizing psychosocial elements. It emphasizes the need to educate patients on the biopsychosocial model, facilitate better care, and dispel misconceptions.

The high prevalence and the debilitating nature of pain following cancer urge the need for appropriate pain assessment and management in this population. Yet cancer pain remains under-recognized and under-treated. For effective pain management, correct identification of the presence of different underlying pain mechanisms is warranted, since pain management strategies differ considerably according to the predominant mechanisms. To raise awareness around possible underlying pain mechanisms in pain after cancer, the three major pain mechanisms are shortly explained and translated to this specific population. Next, in this Special Issue, we delve further into the existing evidence on the presence of these pain mechanisms in patients with pain after cancer, and on how they can be assessed or approached in patients with pain after cancer.

Background The Ehlers-Danlos syndromes (EDS) are a paradigm group of rare heritable connective tissue disorders caused by pathogenic defects in genes involved in biosynthesis, fibrillogenesis, and/or supramolecular organization of collagen fibrils in the extracellular matrix (ECM). Joint hypermobility, skin hyperextensibility, abnormal wound healing and easy bruising are among the cardinal clinical features. The classical EDS type, caused by caused by defects in type V or rarely type I collagen, is the most prevalent genetically elucidated EDS type [1].(Chronic) pain is highly prevalent in individuals with EDS and is one of the foremost reasons these individuals seek medical attention. There is a high use of analgesics, surgery, and physical therapy but these treatment modalities often bring only modest relief at best, and some are associated with unwanted side effects. Few studies, almost exclusively conducted in the molecularly unexplained hypermobile EDS type, have brought limited evidence for neuropathic pain and decreased intra-epidermal nerve fiber density. Interestingly, functional and structural abnormalities of the nervous system and associated pain-related behaviors have also been described in mouse models of EDS [2]. Comprehensive human studies on pain prevalence and pain mechanisms in molecularly solved EDS types are however currently not available, thereby representing a major gap in the study of pain in EDS. Objectives The primary aim of this cross-sectional study was to identify the sensory profile of individuals with cEDS. Secondly, we aimed to identify the pain characteristics and the emotional-cognitive burden in cEDS. Methods Nineteen individuals with molecularly confirmed cEDS and 19 healthy matched control were recruited. Sensory profiling included sensitivity to innocuous and noxious stimuli of multiple modalities (electrical, thermal, vibration, touch, pressure) and a parallel and sequential conditioned pain modulation protocol. Moreover, pain characteristics and emotional-cognitive factors that are known to influence pain processing were studied using a set of validated questionnaires (PD-Q, DN4, HADS, HAQ, SF-36, CSI, PVAQ, TAMPA scale). Results: The cEDS cohort showed an altered sensory profile. Higher (p=0.04) detection thresholds for vibration stimuli at the lower limb were found indicating the presence of hypoesthesia. Reduced/altered thermal sensitivity was found with significantly more (p<0.001) paradoxical thermal sensations at the lower limb (usually to heat). Lower pain thresholds were found to mechanical (p<0.001) stimuli at both the upper and lower limbs and to cold (p=0.005) stimulation at the lower limb indicating hyperalgesia.Using a parallel conditioned pain paradigm, significantly (p=0.005 and p=0.046) smaller antinociceptive responses were shown in cEDS suggestive of impaired central pain inhibition. Conclusion This study represents the first systematic investigation of pain in a genetically defined EDS type. With evidence for sensory changes and impaired pain modulation in cEDS, we provide new insights on the possible role of the ECM in the development and persistence of pain. References [1] Malfait et al. Am J Med Genet C Semin Med Genet 2021;187(4):429-445.[2] Malfait et al. Nat. Rev. Dis. Primers 2020;6(1):64. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1.cEDS cohort compared to control groupPain+Emotional burden(+)Detection thresholdsElectrical=Thermal=Vibration+Touch=Paradoxical thermal sensations+Pain thresholdsElectrical=Cold-Heat=Pressure-Conditioned pain modulation-+/-: statistically significant differences; = non-significant

This chapter provides an overview of the current understanding of physical activity in patients with chronic fatigue syndrome (CFS). It discusses research data concerning CFS physical activity levels and patterns, and explains that effective treatments are available to improve physical activity levels in patients with CFS. The chapter addresses some methodological issues and directions for future research in this important area. Based on their behavior, patients with CFS can be categorized in two subgroups. One group comprises those who feel helpless and avoid activity, resulting in extremely passive behavior. The second group displays a highly variable activity pattern. Self-management for people with CFS involves encouraging them to pace their activities and respect their physical and mental limitations. Physical activity monitoring in CFS research has been conducted with accelerometers worn at the wrist or the leg. Both of these anatomical locations might generate somewhat biased findings.

Background Knee osteoarthritis (KOA) is a heterogenous disease, meaning individuals can present with various signs and symptoms related to different biopsychosocial (BPS) factors [1,2]. Several phenotypes can as such be expected. Phenotyping KOA patients, specifically those awaiting total knee arthroplasty (TKA), could be relevant, because a substantial part of patients (20%) reports chronic post-TKA pain [3]. Various preoperative phenotypic factors related to domains of the BPS model have been described, but consensus and a classification of patients based on these factors is still lacking [4–7]. Objectives The aim of this exploratory study is to identify phenotypes based on BPS related factors in KOA patients awaiting TKA. Methods Participants were included if they were diagnosed with KOA and waiting for TKA surgery in one of the four participating hospitals in Belgium and the Netherlands. A cross-sectional latent profile analysis was conducted in MPlus [8] containing the grade of KOA before TKA surgery (structural variable); body mass index and glycated hemoglobin value (metabolic variables); isometric strength of m. Quadriceps and m. Hamstrings of the affected leg, proprioceptive accuracy of the affected leg, and physical function (functional variables); pain intensity scores and symptoms related to altered somatosensory processing (pain-related variables); pain catastrophizing, depression, anxiety symptoms, expectations and satisfaction (psychological variables); and work and education level (social variables). Data were checked for multicollinearity and multivariate outliers. The ideal model was chosen based on qualitative evaluation, goodness of fit and classification uncertainty. Results 224 participants were included of which 109 women (65.19 +/- 8.18 years old) and 108 men (66.92 +/- 7.18 years old). A model with 2 phenotypes was found to be most appropriate. Both phenotypes differed in 13 out of 19 continuous variables. Phenotype 1 (72% of all participants) was characterized by scoring better on at least one of all metabolic, functional, psychological and pain-related continuous variables compared to phenotype 2 (28% of all participants), except for glycated hemoglobin value, proprioception, expectations, and widespread temporal summation and conditioned pain modulation (part of somatosensory processing variables). Concerning categorical variables, phenotype 1 (72%) was characterized by having a lower probability to have a Kellgren & Lawrence (K&L) scale 2 compared with patients in phenotype 2 (28%). The probabilities of the other categorical variables did not differ between the two phenotypes. Conclusion A model with 2 phenotypes in KOA patients awaiting TKA appeared the most appropriate, which confirmed the existence of a group that experiences disturbed somatosensory processing signs in combination with worse results on psychological (pain catastrophizing, fear and depression), functional (strength and physical function), structural (higher possibility to have a K&L grade 2 compared to the other phenotype) and metabolic factors (body mass index), and a group that does not present this disruption in combination with better results on the aforementioned BPS factors. Further research is necessary and should also investigate if different phenotypes react differently regarding treatment outcome after TKA. References [1]Dell'Isola, A. et al. PLoS One 13, e0191045 (2018)[2]Bierma-Zeinstra, S. M. A. et al. Arthritis Res. Ther. 13, 213 (2011)[3]Sayah, S. M. et al. J. Arthroplasty 36, 3993-4002.e37 (2021)[4]Baert, I. A. et al. Osteoarthritis Cartilage 24, 213–23 (2016)[5]Wylde, V. et al. BMJ Open 7, e018105 (2017)[6]Petersen, K. K.-S. Scand. J. Pain (2022)[7]Laferton, J. A. C. et al. Health Psychol. Rev. 16, 50–66 (2022)[8]Muthén, L. K., et al. (2017) Acknowledgements: NIL. Disclosure of Interests Sophie Vervullens: None declared, Lotte Meert: None declared, Gavin Van der Nest: None declared, Jonas Verbrugghe: None declared, Peter Verdonk: None declared, Frank Rahussen: None declared, Rob Smeets Grant/research support from: Global Awards for Advancing Chronic Pain Research (ADVANCE) 2021 ID#70107413 –> However not used for this study., Mira Meeus: None declared.Figure 1

IntroductionPeople with haemophilia (PwH) suffer from knee and ankle joint pain, but the association with structural damage remains underexplored. They report activity limitations but it is unclear which factors contribute to lower limb activity limitations (LL-AL). AimsThis study aimed (i) to analyse the association between ankle joint pain and structure and (ii) explore the contribution of haemophilia-related, individual and psychological factors to LL-AL in PwH. MethodsThis study included 104 moderate/severe PwH. Ankle pain intensity was assessed with a numeric rating scale and pain sensitivity with algometry (pressure pain threshold (PPTA)). Ankle structure was assessed with MRI (IPSG-MRI) and ultrasound (HEAD-US), joint health with the Haemophilia Joint Health Score (HJHS). The HAL-LOWCOM subscore evaluated LL-AL. A Spearman correlation analysed the correlation between ankle pain and structure. The contribution of haemophilia-related factors (joint health, overall pain (Brief Pain Inventory-Pain Severity (BPI-PS)), functional status (2-Minute-Walking-Distance, Timed Up and Go); individual factors (age, BMI) and psychological factors (fear and avoidance beliefs over physical activity (FABQ-PA) and work (FABQ-Work), anxiety and depression) to LL-AL was explored using a regression analysis. ResultsOnly low correlations were found between ankle pain intensity and structure (IPSG-MRI, HEAD-US). PPTA was unrelated to structure. Altogether, HJHS, overall pain (BPI-PS), FABQ-Work and age explained 69% of HAL-LOWCOM variance, with 65% explained by the combination of HJHS and BPI-PS. ConclusionNo meaningful associations were found between ankle pain and structural damage, suggesting that other factors may contribute to PwH's ankle pain. In contrast, mainly haemophilia-related factors explained LL-AL variance.

PURPOSE The purpose of this paper was first to gain an in-depth understanding of the barriers and facilitators to implementing the BPS model and pain neuroscience education in the current Lebanese physical therapy health care approach and explore its acceptability. METHOD A qualitative semi-structured interview using purposive sampling was conducted with eight Lebanese physical therapists practising in different governorates. The transcribed text from the interviews was analyzed using inductive thematic analysis. RESULTS Two topics were generated and constructed by the researchers: (1) "barriers to the implementation of pain neuroscience education, with subthemes including (a) "current health care approach," (b) "basic curriculum and continuing education," (c) "patients' barriers"; (2) "facilitators to the implementation of pain neuroscience education," with subthemes containing (a) "interest in the BPS model, (b) "therapeutic alliance," and (c) "motivation for future training on BPS approach." CONCLUSION The analysis of the results showed that Lebanese physical therapists currently hold a strong biomedical view of chronic pain, assessment, and treatment. However, despite the presence of barriers and challenges, they are aware and open to consider the implementation and future training about the BPS model and pain neuroscience education in their approach.IMPLICATIONS FOR REHABILITATIONThe exploration of potential barriers and facilitators to the bio-psychosocial model and pain neuroscience education implementation may provide an opportunity for better development and design of a culturally sensitive pain neuroscience education material for Arab-speaking and Lebanese physical therapists.The exploration of barriers and facilitators to the implementation of pain neuroscience education will help to improve pain education and ensure better clinical pain management.The most important barriers were the dominant characteristic of the Lebanese physical therapist's health approach, which is focused on a biomechanically oriented model, and their lack of knowledge to approach chronic pain from a biopsychosocial perspective.

We identified three axes: The importance of basic and translational research is universally acknowledged, but many experimental pain models remain focused on reflexive responses, which are largely irrelevant to human pain. Animal models of transition from acute to chronic pain are virtually absent—a crucial problem in human pain research, and back-translational research remains underdeveloped (Mouraux et al., 2021). Improving methods to mimic aspects of pathological pain in humans is urgent to understand pathophysiology and to back translate to animal research with translatable biomarkers for treatment development (Quesada et al., 2021). Despite significant therapeutic advances in the last decade (CGRP inhibitors in chronic migraine, topical procedures for peripheral neuropathic pain, intrathecal ziconotide in malignant and non-malignant pain), most pharmacological pain interventions have been in use for decades, and provide limited long-term benefits (Mouraux et al., 2021). For most treatments, we do not know why they work or fail, and this black box needs to be addressed by examining mechanisms through which interventions exert effects on outcomes. By identifying mechanisms, we can refine interventions to improve their effectiveness and implementation. Predictive factors have been validated regarding chronic pain after neural lesions, surgical trauma or psychological distress; however, their clinical implementation is unsatisfactory, partly because lack of translation to the clinics of the procedures on which adequate predictors rely. European consortia such as IMI-PainCare aim at profiling functional indicators of pain development and drug effects using biomarkers derived from pain descriptors, non-invasive neurophysiological procedures and imaging measurements. While the Dolorisk consortium aims at analysing potential predictors of chronic pain and response to therapy towards personalized medicine. Better treatments will only emerge when we have a better understanding of pathophysiology of different pain types in specific populations (e.g. those with cognitive impairment, mental health disorders) across the lifespan. Non-pharmacological treatments such as neuromodulation, manual therapy and exercise have shown efficacy in a variety of pain conditions, but in the absence of personalization, they will remain confronted with ceiling effects. Psychological approaches have demonstrated efficacy but barriers to uptake, including stigma, need to be addressed. There is great enthusiasm for digital approaches such as smartphone apps and virtual reality, but we need to robustly test their benefits and harms. Artificial intelligence is getting more popular, but we have yet to unlock its potential to aid appropriate diagnosis and prognosis. Focus on cutting-edge digital techniques may underlie some neglect of the ‘social’ in the biopsychosocial model—and there is a great need to both understand the mechanisms by which social factors contribute to pain, and how we can tackle them. A major issue is closing the large evidence-practice gaps that persist in the management of pain. The attempts worldwide to improve uptake of evidence have yielded disappointing results. What we consider ‘optimal’ evidence often stems from clinical trials that may not represent the actual patients healthcare professionals treat. For instance, excluding subjects from trials due to co-morbidities and demographics is common practice that severely reduces generalizability of results. Understanding interactions between pain disorders and their co-morbidities and the effect of targeting co-morbidities on pain-related disability is crucial (Voute et al., 2023). Ineffective and often aggressive treatments are still overused, for example, in musculoskeletal pain conditions, while effective and safe treatments remain underused (Maher et al., 2019). Patients are largely absent from care decisions. Providing appropriate care needs to consider patients' health literacy, values, expectations, culture, and preferences to ensure shared decisions are made. Research questions and interventions—where possible, should be codesigned with patients, target patient important outcomes and support their self-management efforts. This Strategy aims not only to enable high-quality and meaningful research, but also maximize its translation into European policy and practice. Thanks to EFIC's leadership, collaborations and communication infrastructure, we believe it will herald better treatments for pain, increase the profile of European pain research and advocate for pain research funding.

Background Conflicting results exist between somatosensory profiles of patients with temporomandibular myalgia (TMDm). The objective of this review was to examine whether adults with TMDm show altered responses to dynamic quantitative sensory tests compared with healthy controls. Methods We searched five electronic databases for studies, excluding those without suitable controls or where TMDm was associated with confounding non-musculoskeletal disorders. Risk of bias was assessed with the SIGN case-control study checklist. Findings were structured around dynamic quantitative sensory tests and their localization. Where possible, we performed meta-analysis with a random inverse variance model to compare patients with TMDm and healthy controls. Statistical heterogeneity was estimated with Chi(2) test and inconsistency index, I-2. Results We extracted data from 23 studies comprising 1284 adults with chronic TMDm and 2791 healthy controls. Risk of bias was assessed as high for 20 studies. Mechanical temporal summation, the most studied phenomenon (14 studies), is increased in the upper limb of patients with TMDm (SMD = 0.43; 95% CI: .11 to .75; p = .009) but not in the jaw area (p = .09) or in the cervical area (p = .29). Very little evidence for altered thermal temporal summation (five studies), conditioned pain modulation (seven studies), exercise-induced hypoalgesia (two studies), placebo analgesia (two studies), stress-induced hypoalgesia (one study) and offset analgesia (one study) was found. Discussion A major limitation of this review was the risk of bias of included studies. Future studies would benefit from following methodological guidelines and consideration of confounding factors.

PSiM IV – Pain Practice Investigating shortterm habituation to pain with FMRI – A protocol integrating selfreport, block and trialbytrial analyses MM van der Miesen; AL Kaas; CJ Vossen; EA Joosten; DEJ Linden; JC Peters Department of Anesthesiology and Pain Management, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; Department of Cognitive Neuroscience, Maastricht University, Maastricht, The Netherlands; Department of Anesthesiology, Maastricht University Medical Centre, Maastricht, The Netherlands; School of Mental Health and Neuroscience, Maastricht University, Maastricht,

Psychologically based interventions aim to improve pain-related functioning by targeting pain-related fears, cognitions and behaviors. Mediation and moderation analyses permit further examination of the effect of treatment on an outcome. This systematic review and meta-analysis aims to synthetize the evidence of specific mediators and moderators (i.e., treatment targets) of psychologically based treatment effects on pain and disability. A total of 28 mediation and 11 moderation analyses were included. Thirteen mediation studies were included in a meta-analysis, and the rest was narratively synthetized. Reductions in pain-related fear (indirect effect [IE]: -0.07; 95% confidence interval [CI]: -0.11, -0.04) and catastrophizing (IE: -0.07; 95%CI: -0.14, -0.00), as well as increases in self-efficacy (IE: -0.07; 95%CI: -0.11, -0.04), mediated effects of cognitive behavioral therapy on disability but not on pain intensity, when compared to control treatments. Enhancing pain acceptance (IE: -0.17; 95%CI: -0.31, -0.03) and psychological flexibility (IE: -0.30; 95%CI: -0.41, -0.18) mediated acceptance and commitment therapy effects on disability. The narrative synthesis showed conflicting evidence, which did not support a robust moderated effect for any of the examined constructs. Overall, the methodological quality regarding mediation was low, and some key pitfalls are highlighted alongside recommendations to provide a platform for future research.

OBJECTIVE This systematic review summarizes the relevant literature on the effectiveness of tailored interventions in non-specific low back pain (NSLBP). METHODS The search strategy has been executed in December 2019 in the electronic databases PubMed, Web of Science and Embase. Study selection, data extraction and quality assessment were done independently by two authors. RESULTS A total six eligible studies were identified. Five out of six articles used a classification system to subgroup patients. All active patient tailored interventions had similar or better results than the non-patient tailored interventions, most importantly on pain (short- and mid-term, not for long term follow-up). Two motor control interventions revealed sustained or increased effects at 12 months follow-up for disability. For cost-effectiveness, medication use and work absenteeism, results were inconclusive. Global rating of change evaluation confirmed significant between-group results at 10 weeks to 4 months follow-up, but results were not maintained at 12-month evaluation. DISCUSSION & CONCLUSION: Our findings support the preliminary evidence for the use of patient tailored treatment for reductions in pain and disability. However, our results are of very low to moderate quality evidence and the observed effects strongly depend on the subgroups and the chosen interventions. More high-quality RCT's with homogenous designs and larger sample sizes are needed.

The current systematic review aimed to compare the effect of injury-focused (specific) exercises versus more general (non-specific) exercises on pain in patients with chronic neck or shoulder pain. We searched PubMed, EMBASE, and Web of Science. Two reviewers screened and selected studies, extracted outcomes, assessed risk of bias, and rated the quality of evidence. A total of nine eligible studies, represented in 13 articles, were identified, with a considerable risk of bias. One article investigated the acute effect of single bouts of exercise on pain and reported an immediate pain reduction after non-specific exercise. Regarding short-term effects, seven out of the nine studies found no differences in pain between interventions, with inconsistent results among two other studies. Concerning the long-term effects, while pain reduction seems to be favored by specific exercises (two out of four articles), the best format is still unclear. Based on the acute effects, a single bout of non-specific exercise seems to be a better option for pain-relief for patients with chronic neck or shoulder pain. For short-term effects, there are no differences in pain between specific and non-specific exercises. Regarding long-term effects, specific exercises seem to be the best option. Nevertheless, more studies are warranted.

BACKGROUND AND OBJECTIVE:After whiplash injury, some patients develop chronic whiplash-associated disorders. The exact pathophysiology of this chronification is still unclear and more knowledge is needed regarding the different post-injury phases. Therefore, studies were searched that examined temporal changes in pain processing, measured by Quantitative Sensory Testing (QST).DATABASES AND DATA TREATMENT:This systematic review searched three electronic databases (Medline, Web of Science and Embase) for articles meeting the eligibility requirements. Risk of bias was assessed according to a modified Newcastle-Ottawa Scale.RESULTS:The 12 included studies presented moderate to good methodological quality. These studies showed altered pain processing within the first month after injury and normalization within 3 months in 59%-78% of the patients. After 3 months, recovery stagnates during the following years. Thermal and widespread mechanical hyperalgesia occur already in the acute phase, but only in eventually non-recovered patients.CONCLUSIONS:Differences in pain processing between recovering and non-recovering patients can be observed already in the acute phase. Early screening for signs of altered pain processing can identify patients with high risk for chronification. These insights in temporal changes show the importance of rehabilitation in the acute phase. Future research should target to develop a standardized (bed-site) QST protocol and collect normative data which could, in relation with self-reported pain parameters, allow clinicians to identify the risk for chronification.SIGNIFICANCE:Altered pain processing is present soon after whiplash injury, but usually recovers within 3 months. Non-recovering patients show little to no improvements in the following years. Differences between recovering and non-recovering patients can be observed by Quantitative Sensory Testing already in the acute phase. Therefore, it is considered a feasible and effective tool that can contribute to the identification of high-risk patients and the prevention of chronification.