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Persistent pain despite satisfactory disease treatment is frequent in rheumatoid arthritis (RA) and spondyloarthritis (Spa) and may result from specific changes in central pain processing. We assessed these mechanisms further by systematically comparing thermal pain thresholds and conditioned pain modulation (CPM) between patients with active RA or Spa and healthy controls. We included 50 patients with RA and 50 patients with Spa and 100 age-matched and sex-matched controls. Heat and cold pain thresholds (HPT-CPT) were measured on the dominant forearm, and CPM was assessed by applying conditioning stimuli (immersion in a cold-water bath) to one foot and the nondominant hand in 2 successive randomized sequences. Descending pain modulation was assessed as the difference in HPTs (in °C) before and after conditioning. Larger HPT differences (ie, a larger CPM effect) reflected more efficient descending inhibition. Potential associations between changes in CPM and clinical data, including disease activity, pain intensity, and psychological and functional variables, were systematically assessed. Heat pain threshold and cold pain threshold were similar in patients and controls. The mean CPM effect was significantly weaker in patients than that in controls for conditioning applied to either the foot (0.25°C ±2.57 vs 2.79°C ±2.31; P0.001) or the nondominant hand (0.57°C ±2.74 vs 2.68°C ±2.12; P0.001). The smaller CPM effect in patients was correlated with average pain intensity, but not with disease activity or other clinical characteristics, suggesting a significant pathophysiological role for changes in endogenous pain modulation in the mechanisms of chronic pain associated with inflammatory rheumatism.

This chapter presents the case of a 42-year-old woman with rheumatoid arthritis (RA) who describes tingling, pins and needles and sometimes burning pain at the right wrist and palmar area of the thumb and index, extending to the forearm. Clinical examination shows no sensorimotor deficit, and percussion of the median nerve at the wrist induces paresthesia. Carpal tunnel syndrome is frequent in RA and mainly a clinical diagnosis. Complementary explorations are not always mandatory. Nerve conduction studies may provide objective confirmation of decreased sensory and motor conduction of the median nerve at the wrist. Imaging particularly using ultrasound can help when there is strong suspicion of a local cause of compression. Nonsurgical treatment includes rest, splinting, and local corticosteroid injections. In refractory cases or when there is motor involvement, surgical decompression is indicated.

Resumen Objectifs: Si l’on considere le vaste perimetre que couvre la rhumatologie et la prevalence de la douleur au cœur de cette specialite, il nous a semble necessaire de mener une etude sur les habitudes de prescription dans le contexte de l’epidemie internationale des opioides et compte tenu de l’efficacite moderee des opioides forts dans le traitement des affections osteo-articulaires chroniques. Nous avons compare les pratiques de prescription d’opioides en rhumatologie francaise dans la douleur chronique non cancereuse et propose des recommandations de bonne pratique clinique. Methodes: Nous avons realise une etude transversale de la base de donnees de l’assurance maladie en France, incluant tous les patients âges de 16 ans ou plus ayant recu au moins un opioide fort sur prescription d’un rhumatologue en 2015. Une enquete nationale aupres de tous les rhumatologues francais a ete realisee en juin 2015 a l’aide d’un questionnaire en 47 items. Resultats: Seuls 2,4 % des patients ayant recu un opioide fort en 2015 (n = 700 946) avaient au moins une prescription d’un rhumatologue. Les rhumatologues prescrivaient davantage de morphine et significativement moins d’oxycodone et de fentanyl (p Conclusions: Pour soulager la douleur chronique non cancereuse, les rhumatologues prescrivaient generalement des opioides pour une courte duree, a des doses reduites, majoritairement en adequation avec les recommandations nationales. La formation a la prise en charge de la douleur influencait la prescription d’opioides par les rhumatologues.

We describe here the development and validation of the Osteoarthritis Symptom Inventory Scale (OASIS), a new self-administered questionnaire specifically designed to evaluate the various osteoarthritis (OA) pain symptoms with different dimensions related to OA pain mechanisms. The initial development phase and qualitative study generated a list of 17 descriptors reflecting OA pain and other associated symptoms, leading to the first version of the questionnaire (OASIS17). Each item was quantified on a 0-10 numerical scale. Validation was performed using 123 consecutive patients with OA pain recruited at 28 centers in France, mainly general practitioner offices. Validation involved: (i) determining the questionnaire's factorial structure through exploratory and confirmatory analyses, (ii) analyzing convergent and divergent validities (i.e., construct validity), (iii) assessing each item's test-retest reliability, and (iv) evaluating OASIS's ability to detect treatment effects (i.e., sensitivity to change). The final OASIS version includes nine items discriminating and quantifying three distinct, clinically relevant OA pain dimensions sensitive to treatment. OASIS9's psychometric properties suggest that it could improve the characterization of OA pain profiles for three clinically relevant domains: localized, neuropathic-like, and deep pain. The OASIS9 questionnaire could be used to phenotype OA pain patients and identify responders to various therapeutic interventions as a function of OA pain dimensions.

Resume La douleur est la principale manifestation clinique de l’arthrose. Elle n’est pas simplement un message nociceptif associe a la destruction articulaire. La douleur-symptome est une maladie a part entiere. La douleur dans l’arthrose presente plusieurs composantes : nociceptive, neuropathique et nociplastique. Au-dela de l’evaluation de son intensite et de son retentissement, l’evaluation par autoquestionnaires permet a la fois de depister les differentes composantes de la douleur et l’experience du patient (DN4, ICOAP, OASIS). A terme, phenotyper les patients arthrosiques selon les composantes de la douleur et leur experience permettrait une prise en charge personnalisee.

Multidisciplinary approaches to treating chronic pain have been proven effective. Currently, chronic pain patients face lengthy waitlists in pain medicine departments. To overcome this problem, we developed the "FastSchool" program to educate patients about pain management and treatment. In this study, we evaluated the benefit of a "FastSchool" session on pain and catastrophizing in chronic pain patients.Included patients had chronic non-cancer pain, no more than 2 visits to a pain medicine department. Patients attended a single 3-hour session, conducted by an interprofessional team. Four topics were addressed: chronic pain mechanisms, pharmacological therapies, physical activity, and the management of analgesics. Patients completed questionnaires at baseline and at 3 months post-session to assess pain interference, pain intensity, and catastrophizing.The study population included 88 patients; 71 completed the follow-up questionnaires. Pain interference (p = 0.002), average pain intensity (p = 0.013), and catastrophizing (p 0.001) decreased 3 months after FastSchool. At M3, 35 % of patients felt their pain had improved based on the Patient Global Impression of Change.FastSchool, an innovative short-term educational program inspired by cognitive behavioral therapy, showed positive results in reducing pain impact.Implementation of FastSchool in pain medicine departments would reduce waitlist times for non-pharmacological treatment.

Background Pain remains a prevalent symptom for rheumatoid arthritis (RA) patients despite a wide therapeutic choice. The objective of this study was to provide a multidimensional evaluation of pain. Methods A total of 295 RA patients from 7 French rheumatology centres were enrolled in a cross‐sectional study. Patients completed a chronic pain assessment questionnaire approved by the French National Authority for Health, the health assessment questionnaire (HAQ) as well as depression and anxiety scales (HAD, Beck Depression Inventory, STAI). Disease activity (DAS28) and ESR were recorded. A multivariate descriptive analysis was undertaken using principal component analysis (PCA). Results 38.4% of patients had a pain score > 40 mm/100, although 83% were on biological treatment and 38.7% were in remission based on the RA activity score. The PCA analysis found four axes representing 70% of total variance. The axes, per cent of variance and variables represented were as follows: (a) axis 1, 41% variance, anxiety and depression scores, sensory and affective qualifier score, HAQ and pain impact on daily life; (b) axis 2, 13% variance, disease activity score (DAS28) and pain relief with current treatment; (c) axis 3, 9% of variance, RA duration and radiographic score and (d) axis 4, 6% of variance, DAS28 and ESR. Moderate to severe pain was significantly associated with axes 1 and 2. Conclusions Despite a high proportion of patients on biological treatments, 38.4% of patients continue to experience moderate to severe pain. Pain is associated with the RA activity score, but also with the depression and anxiety scores. Significance Substantial proportion of rheumatoid arthritis (RA) patients still experiences relevant pain, although more than 80% on biological treatment. Pain is primarily associated with anxiety and depression scores and with disease activity score. These findings highlight the need to assess patients’ mental well‐being alongside. Clinical measures of disease activity to better manage pain and guide treatment decisions.

BACKGROUND: There is considerable public interest in whether Europe is facing an opioid crisis comparable to the one in the United States and the contribution of opioid prescriptions for pain to a potential opioid crisis. METHODS: A task force of the European Pain Federation (EFIC) conducted a survey with its national chapter representatives on trends of opioid prescriptions and of drug-related emergency departments and substance use disorder treatment admissions and of deaths as proxies of opioid-related harms over the last 20 years. RESULTS: Data from 25 European countries were received. In most European countries opioid prescriptions increased from 2004 to 2016. The levels of opioid consumption and their increase differed between countries. Some Eastern European countries still have a low opioid consumption. Opioids are mainly prescribed for acute pain and chronic noncancer pain in some Western and Northern European countries. There was a parallel increase in opioid prescriptions and some proxies of opioid-related harms in France, Finland and the Netherlands, but not in Germany, Spain and Norway. In United Kingdom, opioid overdose deaths, but not opioid prescriptions increased between 2016 and 2018. There are no robust data available on whether prescribed opioids for pain patients contributed to opioid-related harms. CONCLUSIONS: There are marked differences between European countries in trends of opioid prescribing and of proxies for opioid-related harms. Europe as a whole is not facing an opioid crisis. Discussions on the potential harms of opioids should not obstruct their prescription for cancer pain and palliative care. SIGNIFICANCE: Europe as a whole is not facing an opioid crisis. Some Eastern European countries have limited access to opioid medicines. Discussions on the potential harms of opioid medicines for noncancer pain should not obstruct opioid therapy for cancer therapy and palliative care. ispartof: EUROPEAN JOURNAL OF PAIN vol:25 issue:8 pages:1760-1769 ispartof: location:England status: published

The major therapeutic challenge in inflammatory rheumatic diseases is the persistence of pain despite good responses to specific therapies. Central sensitization, which can be assessed clinically by psychophysical measurements, including quantitative sensory testing (QST), is a widely proposed mechanism for chronic pain. In this systematic review, we explored the scientific literature addressing quantitative sensory testing in inflammatory rheumatic diseases. We searched Pubmed and Embase for publications up to December 2021 concerning studies on quantitative sensory testing focusing on pain thresholds, temporal summation (TS) and conditioned pain modulation (CPM), in adult patients with chronic inflammatory rheumatism (e.g. rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, juvenile idiopathic arthritis). The exclusion criteria were reviews, inclusion of children and no reported pain threshold. Data quality was assessed with the National Institutes of Health (NIH) Quality Assessment tools. We identified 27 studies (18 controlled, 9 uncontrolled) including 1875 patients with inflammatory rheumatic diseases and 795 controls. A decrease in pressure pain threshold, in favor of allodynia, was found in 12 of 14 controlled studies on patients with rheumatoid arthritis and spondyloarthritis. The results of other psychophysical tests, including TS and CPM, were inconsistent due to population heterogeneity and a lack of standardization of the patients' disease duration, activity and treatment. Our review shows that pain in chronic inflammatory rheumatism is associated with pressure allodynia. However, given the heterogeneous quality and discrepant results of studies of other QST outcome measures, the hypothesis of central sensitization involvement in pain processing in these patients cannot be confirmed.

Background Chronic pain affects approximately 30% of the general population, severely degrades quality of life (especially in older adults) and professional life (inability or reduction in the ability to work and loss of employment), and leads to billions in additional health care costs. Moreover, available painkillers are old, with limited efficacy and can cause significant adverse effects. Thus, there is a need for innovation in the management of chronic pain. Better characterization of patients could help to identify the predictors of successful treatments, and thus, guide physicians in the initial choice of treatment and in the follow-up of their patients. Nevertheless, current assessments of patients with chronic pain provide only fragmentary data on painful daily experiences. Real-life monitoring of subjective and objective markers of chronic pain using mobile health (mHealth) programs can address this issue. Objective We hypothesized that regular patient self-monitoring using an mHealth app would lead physicians to obtain deeper understanding and new insight into patients with chronic pain and that, for patients, regular self-monitoring using an mHealth app would play a positive therapeutic role and improve adherence to treatment. We aimed to evaluate the feasibility and acceptability of a new mHealth app called eDOL. Methods We conducted an observational study to assess the feasibility and acceptability of the eDOL tool. Patients completed several questionnaires using the tool over a period of 2 weeks and repeated assessments weekly over a period of 3 months. Physicians saw their patients at a follow-up visit that took place at least 3 months after the inclusion visit. A composite criterion of the acceptability and feasibility of the eDOL tool was calculated after the completion of study using satisfaction surveys from both patients and physicians. Results Data from 105 patients (of 133 who were included) were analyzed. The rate of adherence was 61.9% (65/105) after 3 months. The median acceptability score was 7 (out of 10) for both patients and physicians. There was a high rate of completion of the baseline questionnaires and assessments (mean 89.3%), and a low rate of completion of the follow-up questionnaires and assessments (63.8% (67/105) and 61.9% (65/105) respectively). We were also able to characterize subgroups of patients and determine a profile of those who adhered to eDOL. We obtained 4 clusters that differ from each other in their biopsychosocial characteristics. Cluster 4 corresponds to patients with more disabling chronic pain (daily impact and comorbidities) and vice versa for cluster 1. Conclusions This work demonstrates that eDOL is highly feasible and acceptable for both patients with chronic pain and their physicians. It also shows that such a tool can integrate many parameters to ensure the detailed characterization of patients for future research works and pain management. Trial Registration ClinicalTrial.gov NCT03931694; http://clinicaltrials.gov/ct2/show/NCT03931694

BACKGROUND Chronic pain affects approximately 30% of the general population, severely degrades quality of life (especially in older adults) and professional life (inability or reduction in the ability to work and loss of employment), and leads to billions in additional health care costs. Moreover, available painkillers are old, with limited efficacy and can cause significant adverse effects. Thus, there is a need for innovation in the management of chronic pain. Better characterization of patients could help to identify the predictors of successful treatments, and thus, guide physicians in the initial choice of treatment and in the follow-up of their patients. Nevertheless, current assessments of patients with chronic pain provide only fragmentary data on painful daily experiences. Real-life monitoring of subjective and objective markers of chronic pain using mobile health (mHealth) programs can address this issue. OBJECTIVE We hypothesized that regular patient self-monitoring using an mHealth app would lead physicians to obtain deeper understanding and new insight into patients with chronic pain and that, for patients, regular self-monitoring using an mHealth app would play a positive therapeutic role and improve adherence to treatment. We aimed to evaluate the feasibility and acceptability of a new mHealth app called eDOL. METHODS We conducted an observational study to assess the feasibility and acceptability of the eDOL tool. Patients completed several questionnaires using the tool over a period of 2 weeks and repeated assessments weekly over a period of 3 months. Physicians saw their patients at a follow-up visit that took place at least 3 months after the inclusion visit. A composite criterion of the acceptability and feasibility of the eDOL tool was calculated after the completion of study using satisfaction surveys from both patients and physicians. RESULTS Data from 105 patients (of 133 who were included) were analyzed. The rate of adherence was 61.9% (65/105) after 3 months. The median acceptability score was 7 (out of 10) for both patients and physicians. There was a high rate of completion of the baseline questionnaires and assessments (mean 89.3%), and a low rate of completion of the follow-up questionnaires and assessments (63.8% (67/105) and 61.9% (65/105) respectively). We were also able to characterize subgroups of patients and determine a profile of those who adhered to eDOL. We obtained 4 clusters that differ from each other in their biopsychosocial characteristics. Cluster 4 corresponds to patients with more disabling chronic pain (daily impact and comorbidities) and vice versa for cluster 1. CONCLUSIONS This work demonstrates that eDOL is highly feasible and acceptable for both patients with chronic pain and their physicians. It also shows that such a tool can integrate many parameters to ensure the detailed characterization of patients for future research works and pain management. CLINICALTRIAL ClinicalTrial.gov NCT03931694; http://clinicaltrials.gov/ct2/show/NCT03931694

Resume La douleur du sujet âge est sous-evaluee et difficile a prendre en charge en raison des multiples comorbidites et interactions medicamenteuses specifiques a ces patients. Si plusieurs recommandations internationales existent pour la gestion du traitement de la douleur chez le patient âge, un consensus francais, multidisciplinaire d’experts en douleur et geriatrie a ete publie en 2017 pour guider les prescriptions. Sur le plan pharmacologique, les antalgiques sont utilisables chez le patient âge en respectant certaines precautions. Il faudra principalement introduire les traitements un a un afin de surveiller leur efficacite propre et leur tolerance, il conviendra d’adapter les posologies a l’âge, les insuffisances d’organes et surtout les co-prescriptions. Afin d’optimiser le traitement l’association de therapeutiques non medicamenteuses doit etre envisagee et proposee. Enfin pour favoriser l’observance il conviendra d’expliquer au patient et a son entourage le traitement mis en place, son benefice attendu, ses effets indesirables potentiels.

International audience; OBJECTIVE: To develop guidelines for low back pain management according to previous international guidelines and the updated literature. METHODS: A report was compiled from a review of systematic reviews of guidelines published between 2013 and 2018 and meta-analysis of the management of low back pain published between 2015 and 2018. This report summarized the state-of-the-art scientific knowledge for each predefined area of the guidelines from a critical review of selected literature. A multidisciplinary panel of experts including 17 health professionals involved in low back pain management and 2 patient representatives formulated preliminary guidelines based on the compilation report and a care pathway. The compilation report and preliminary guidelines were submitted to 25 academic institutions and stakeholders for the consultation phase. From responses of academic institutions and stakeholders, the final guidelines were developed. For each area of the guidelines, agreement between experts was assessed by the RAND/UCLA method. RESULTS: The expert panel drafted 32 preliminary recommendations including a care pathway, which was amended after academic institution and stakeholder consultation. The consensus of the multidisciplinary expert panel was assessed for each final guideline: 32 recommendations were assessed as appropriate; none was assessed as uncertain or inappropriate. Strong approval was obtained for 27 recommendations and weak for 5. CONCLUSION: These new guidelines introduce several concepts, including the need to early identify low back pain at risk of chronicity to provide quicker intensive and multidisciplinary management if necessary.

Summary Background Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases. Methods In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609. Findings Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66–6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46–0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55–3·19, p=0·53). Interpretation Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases. Funding None.

Samira Ait Abdellah,1 Caroline Gal,1 Anne Leblanc,2 Anne-Priscille Trouvin,3 Serge Perrot3 1Clinical Research Department, PiLeJe Laboratoire, Paris, France; 2Applied Research Department, PiLeJe Laboratoire, Paris, France; 3Pôle Ostéo-Articulaire, Hôpital Cochin, Paris, FranceCorrespondence: Serge PerrotPôle Ostéo-Articulaire, Hôpital Cochin, 27 Rue Du Faubourg Saint-Jacques, Paris 75014, FranceTel +33 158 411 507Email serge.perrot@aphp.frPurpose: This observational study evaluated a combination of boswellia, turmeric, and red algae extracts in patients with knee osteoarthritis (KOA). Given the growing interest in patient-centered care in osteoarthritis, effects were assessed by an arsenal of patient-reported outcome measures (PROMs): Patient Acceptable Symptom Scale (PASS), Minimal Clinically Important Improvement (MCII), Patient Global Impression of Change (PGIC), and Lequesne algofunctional index (LAFI). Patients also completed a list of 17 items on pain quality.Patients and Methods: Patients with painful unilateral or bilateral KOA had to take 1– 4 capsules per day of a dietary supplement containing boswellia, turmeric, and red algae extracts for 90 days. Patients completed PROMs on Days 0 (baseline), 10, 20, 30, 60, and/or 90.Results: A total of 118 patients [female: 69.5%; age: 62.9 (9.5) years, mean (SD)] were included in the study and took at least one capsule. Mean (SD) follow-up duration was 100.7 (54.9) days. Pain relief was maximal on Day 90: 64.5% of patients were responders (positive PASS); 68.8% and 58.4% had MCII and PGIC scores indicating positive effect (score ≥ 3) or global improvement (score ≥ 5); 73.3% (versus 47.5% at baseline) were mildly/moderately disabled (LAFI score < 8); 55.2% had meaningful decrease (− 30%) in pain intensity (VAS), 35.1% (versus 59.2% at baseline) took analgesics as supplementary treatment. Median time to the first PASS change was 34 days. Pain intensity (VAS), as well as two pain characteristics (ie, “Stabbing pain” and “Widespread pain”), were independent factors associated with non-response on Day 30. Four clusters of responders were isolated according to pain characteristics, with one cluster exhibiting a higher responder rate.Conclusion: The results of this preliminary study suggest that the combination of boswellia, turmeric, and red algae extracts tested could improve KOA patients. Beyond these results, this study showed the importance of PROMs and specific pain qualitative descriptors for the accurate evaluation of dietary supplement approaches in painful conditions.Keywords: Curcuma, dietary supplement, joint disease, Porphyra, self-reported questionnaire

International audience; Pain in rheumatic diseases is primarily due to mechanical or inflammatory mechanism, but neuropathic pain (NP) component is also occurring in many conditions and is probably underdiagnosed. The purpose of this article is to provide an overview of prevalence, pathophysiological and currently available treatment of NP in rheumatic diseases. When associated with clinical evaluation assessing neurological clinical signs and neuroanatomical distribution, Douleur Neuropathique 4 Questions, painDETECT, Leeds assessment of neuropathic symptoms and signs and Neuropathic Pain Questionnaire can detect NP component. Inflammatory or connective diseases, osteoarthritis, back pain or persistent pain after surgery are aetiologies that all may have a neuropathic component. Unlike nociceptive pain, NP does not respond to usual analgesics such as paracetamol and non-steroidal anti-inflammatory drugs. Entrapment neuropathy, peripheral neuropathy or smallfibre neuropathy are different aetiologies that can lead to NP. A part of the pain labelled neuropathic is rather nociplastic, secondary to a central sensitisation mechanism. Identifying the right component of pain (nociceptive vs neuropathic or nociplastic) could help to better manage pain in rheumatic diseases with pharmacological and nonpharmacological treatments.

Background: Knee osteoarthritis (KOA) is a common, painful condition. This open-label, observational, longitudinal study evaluated the use of a fixed combination of boswellia, turmeric, and red algae extracts in patients with painful KOA. Given the growing interest in patient-centred care in osteoarthritis, effects were assessed by an arsenal of patient-reported outcome measures (PROMs): Patient Acceptable Symptom Scale (PASS), Minimal Clinically Important Improvement (MCII), Patient Global Impression of Change (PGIC), and Lequesne algofunctional index (LAFI). Patients also completed a list of 17 items on pain quality.Methods: Patients with painful unilateral or bilateral KOA were included. They had to take 1-4 capsules per day of a dietary supplement containing boswellia, turmeric, and red algae extracts (Cartimotil Fort®, PiLeJe Laboratoire, Paris, France) for 90 days. Patients completed PROMs on Days 0 (baseline), 10, 20, 30, 60, and/or 90. Results: From March 2017 to March 2019, 118 patients [female: 69.5%; age: 62.9 (9.5) years, mean (SD); BMI: 26.4 (4.0) kg/m²; DN4 Conclusions: This study showed that the fixed combination of boswellia, turmeric, and red algae extracts improved KOA patients. Further studies are needed to confirm the observations. Beyond these results, this study showed the importance of PROs and specific pain qualitative descriptors for accurate evaluation of dietary supplement approaches in painful conditions. Trial registration details: ClinicalTrials.gov, NCT02977936. Registered 30 November 2016, https://clinicaltrials.gov/ct2/show/NCT02977936

International audience; Chronic pain is a major public health issue that frequently leads to analgesic opioid prescriptions. These prescriptions could cause addiction issues in high-risk patients with associated comorbidities, especially those of a psychiatric, addictive, and social nature. Pain management in dependent patients is complex and is yet to be established. By combining the views of professionals from various specialties, we conducted an integrative review on this scope. This methodology synthesizes knowledge and results of significant practical studies to provide a narrative overview of the literature. The main results consisted in first proposing definitions that could allow shared vocabulary among health professionals regardless of their specialties. Next, a discussion was conducted around the main strategies for managing prescription opioid dependence, as well as pain in the context of opioid dependence and associated comorbidities. As a conclusion, we proposed to define the contours of holistic management by outlining the main guidelines for creating a multidisciplinary care framework for multi-comorbid patients with chronic pathologies.

Resume Introduction La kinesitherapie est une composante majeure de la prise en charge des douleurs d’origine musculo-squelettique (DMS). Cette etude avait pour objectif d’evaluer la kinesiophobie, son impact et sa prise en charge, dans une population de patients ayant recu une prescription de kinesitherapie pour des DMS. Methodes Une etude nationale prospective multicentrique a ete menee en France chez des patients ayant recu une prescription de kinesitherapie pour des DMS. Le score de kinesiophobie a ete mesure sur l’echelle de Tampa (Tampa Scale of Kinesiophobia [TSK]). La douleur, la satisfaction, la consommation d’antalgiques ont ete evaluees a la premiere visite, a la 5 e seance de kinesitherapie puis a la sortie du programme de reeducation. Resultats Sept cents patients consecutifs souffrant de DMS, dont 54,5 % de femmes, ayant recu une prescription de kinesitherapie, ont ete inclus par 186 medecins generalistes (MG) : 501 avaient un score eleve de kinesiophobie (score TSK > 40). Les patients presentant une kinesiophobie etaient significativement plus âges, avec une activite physique reduite, des douleurs plus intenses et une faible acceptabilite de la douleur. Les patients inclus par un MG ayant une kinesiophobie averee avaient des douleurs et un score de kinesiophobie plus eleves. A l’issue de la 5 e seance de kinesitherapie, la satisfaction globale etait significativement plus elevee chez les patients sans kinesiophobie. On notait une amelioration significative de la satisfaction chez les patients ayant recu une prescription preventive d’antalgiques avant la kinesitherapie, c’est-a-dire 25,6 % d’entre eux. Les facteurs predictifs independants de la prise en charge specifique des douleurs induites par la kinesitherapie etaient : kinesiophobie du patient (OR = 2,02 [1,07–3,82]), traitement antalgique en cours (OR = 2,05 [1,16–3,63]), medecin generaliste ayant suivi un cursus post-these sur la douleur (OR = 2,65 [1,29–5,43]), medecin generaliste exercant dans le secteur prive (OR = 1,88 [1,01–3,48]). Conclusion La kinesiophobie est un processus frequent chez les patients souffrant de DMS, il est associe a la kinesiophobie du MG et diminue la satisfaction du patient vis-a-vis de la kinesitherapie. Une prescription antalgique preventive avant les seances de reeducation permet d’augmenter la satisfaction des patients et doit etre proposee en vue d’ameliorer la prise en charge des DMS.

Introduction L’objectif de cette etude observationnelle etait d’evaluer la reponse a une association d’extraits de boswellia, curcuma, et algue rouge, trois plantes aux proprietes anti-inflammatoires et analgesiques bien connues, chez des patients souffrant de gonarthrose. Les effets ont ete evalues par un arsenal de mesures centrees sur le patient (patient-reported outcome measure [PROMs]). Patients et methodes Les patients souffrant d’une gonarthrose unilaterale ou bilaterale (radiographie Resultats Cent dix-huit patients (femmes : 69,5 % ; âge : 62,9 [9,5] ans, moyenne [ET] ; IMC : 26,4 [4,0] kg/m2 ; DN4 Conclusion Les patients atteints de gonarthrose complementes avec l’association de boswellia, curcuma, et algue rouge testee ont presente une amelioration significative de leur etat quels que soient les caracteristiques de la douleur et leur handicap a l’inclusion. Cette prise en charge a induit une diminution de la consommation de la prise d’antalgiques. Cette etude met egalement en evidence l’importance de l’utilisation de PROMs et de descripteurs qualitatifs de la douleur pour une evaluation individualisee des patients.

Resume Objectifs Evaluer l’efficacite de la rTMS « a large champ » dans la fibromyalgie. Une evaluation multidimensionnelle a ete realisee avec pour critere de jugement principal l’echelle numerique de la douleur et criteres secondaires les scores FIQ, MFI-20, HAD et WPI - SSS. Methodologie Essai clinique monocentrique ouvert, realise en neurophysiologie chez des patients atteints de fibromyalgie consultant au Centre d’evaluation et traitement de la douleur du CHU de Rouen entre novembre 2014 et juin 2016. Les patients etaient inclus sur la base du FIRST, des criteres ACR 1990 et ACR 2010. Les donnees etaient recueillies sur autoquestionnaires a j1, j7, j15 et j30 (EN douleur, scores FIQ, HAD, MFI-20 et WPI–SSS). Un examen clinique avec recherche des points de Yunus etait realise a j1 et j30. Trois seances de stimulations magnetiques transcrâniennes, espacees sur 5 a 8 jours, ont ete realisees pour chaque patient. Les seances comprenaient 30 stimulations, renouvelees 3 fois, soit 90 stimulations par seances. Resultats Vingt-et-un patients ont ete inclus. L’EN douleur, le FIQ et le HAD anxiete etaient significativement ameliores a j7 (respectivement p = 0,004, p = 0,007 et p = 0,049) et cette efficacite persistait jusqu’a j30. L’amelioration de la douleur portait a la fois sur les caracteristiques affectives et sensorielles au QDSA evalue a j30 ( p = 0,02). Le WPI etait significativement ameliore a j7 ( p = 0,049) mais cette efficacite disparaissait au cours du suivi. L’amelioration du MFI etait retardee par rapport aux stimulations (j30, p = 0,04) ainsi que l’amelioration du score HAD depression (j15, p = 0,007 et j30, p = 0,049). Conclusion La rTMS « a large champ » permet une amelioration des patients fibromyalgiques dans les multiples dimensions etudiees. Un essai clinique randomise controle devrait etre realise pour confirmer les resultats preliminaires.

Purpose The prevalence of neuropathic pain is high in the general population, and high priority is given to the management of this pain condition. The treatment of neuropathic pain remains challenging, despite the publication of national and international recommendations. The purpose of this narrative review of venlafaxine (VLX) is to provide a better knowledge of the pharmacology of this drug and a clearer view of its efficacy and tolerability in neuropathic pain. Methods Two independent reviewers searched PubMed with the following search terms: serotonin and noradrenalin reuptake inhibitors OR VLX hydrochloride AND pain . The reviewers included all clinical studies that investigated VLX in neuropathic pain conditions and excluded animal studies, studies on fibromyalgia, studies that focused on the prevention of neuropathic pain, case reports, and studies that did not clearly describe neuropathic pain in the included patients. We describe the 13 studies that we analyzed. Findings Eleven were randomized clinical trials, and the comparator was placebo in 8 studies. Nine studies reported that VLX was effective against neuropathic pain. However, among the trials, only one against placebo included a large number of patients with >200 participants and one against pregabaline and carbamazepine had >200 patients. Most of the adverse events reported in the selected studies were consistent with known adverse events of VLX, and most were mild to moderate. However, most studies were of very short duration. Implications Most of the clinical studies found that VLX was effective and well tolerated. However, given the limited number of study and the limitations of all these studies, further large clinical trials are needed. Currently, considering the limited therapeutic options for treating neuropathic pain and the highly variable nature of responses to all drugs, VLX has a place as a treatment option for neuropathic pain.

Active research is being conducted on musculoskeletal pain, and recent concepts will help clinicians and researchers to develop better approaches: -the new pain taxonomy recently has been modified with a third descriptor with the concept of nociplastic pain. -the latest International Classification of Diseases (ICD-11) includes an IASP task force that developed a new classification system for pain. In this new classification, one can differentiate primary musculoskeletal pain including fibromyalgia and low back pain and secondary musculoskeletal pain related to specific etiologies. -the concept of central sensitization in inflammatory rheumatic diseases is increasingly discussed. In these conditions, even with very active biological treatment, almost a third of patients are still complaining of persisting pain. These persisting pain states under adequate treatment, without any sign of inflammation, led researchers to look for evidence of central sensitization states.

International audience; An endemic increase in the number of deaths attributable to prescribed opioids is found in all developed countries. In 2016 in the USA, more than 46 people died each day from overdoses involving prescription opioids. European data show that the number of patients receiving strong opioids is increasing. In addition, there is an upsurge in hospitalisations for opioid intoxication, opioid abuse and deaths in some European countries. This class of analgesic is increasingly used in many rheumatological pathologies. Cohort studies, in various chronic non-cancer pain (CNCP) (osteoarthritis, chronic low back pain, rheumatoid arthritis, etc), show that between 2% and 8% of patients are treated with strong opioids. In order to help rheumatologists prescribe strong opioids under optimal conditions and to prevent the risk of death, abuse and misuse, recommendations have recently been published (in France in 2016, the recommendations of the French Society of Study and Treatment of Pain, in 2017, the European recommendations of the European Federation of IASP Chapters and the American Society of International Pain Physicians). They agree on the same general principles: opioids may be of interest in situations of CNCP, but their prescription must follow essential rules. It is necessary to make an accurate assessment of the pain and its origin, to formulate therapeutic objectives (pain, function and/or quality of life), to evaluate beforehand the risk of abuse and to get a specialised opinion beyond a certain dose or duration of prescription.

Objectives To study daily pain trajectories (DPT) in patients with knee (KOA) and hip osteoarthritis (HOA) over a one-month period and identify relationships with patients characteristics and acceptability. Methods This prospective, multicenter cohort study was conducted in France by 602 GPs, on outpatients, with painful KOA or HOA. Patients were asked to fill-in a 28-days daily pain diary. DPT were determined by the difference between daily pain and mean pain over 28 days. Pain peaks were defined as an increase of more than 1 point above the mean for up to three consecutive days. The number of pain peaks over the 28 day period allowed classifying the patient's pain trajectory as either “stable” or “unstable”. A logistic regression model was used to identify predicting factors associated with stable pain profile. Results Overall, 1645 patients were included and 886 were analyzed, (56% women, 67.8 years, BMI 27.6 kg/m2, pain 6.0, KOA 71.3%). At one month, stable DPT was found in 59.5% of the patients whatever OA location. In HOA, a shorter duration of disease and pain, a greater disability and in KOA, a more recent disease, morning stiffness ≥ 15 minutes and flare-up were independent factors associated with “stable” DPT. At one month, acceptable pain state was more frequent (65.4%) in patients with stable profiles. Conclusion In lower limb OA, pain is mostly stable over a 28-days period. Pain is better accepted when stable, with different determining factors according location. DPT should be considered when establishing HOA and KOA management.

Resume Objectifs Il est urgent d’ameliorer l’efficacite et la securite d’utilisation des opioides forts dans les douleurs chroniques non cancereuses (DCNC) grâce a des regles de prescription fondees sur les preuves scientifiques. Methodes Les questions cliniques abordees ont ete les suivantes : quelles indications, quels benefices, quels risques et quelles precautions prendre lors de l’utilisation des opioides fors dans la DCNC. Un groupe de travail pluridisciplinaire a elabore des recommandations selon la methodologie proposee par l’HAS. Une recherche systematique de la litterature a ete effectuee sur CENTRAL, MEDLINE et EMBASE. Chaque recommandation a ete evaluee selon la methodologie GRADE. Resultats Vingt et une meta-analyses et 31 etudes de cohorte ont ete selectionnees. Quinze recommandations sont proposees. Les opioides forts ne sont pas recommandes dans la fibromyalgie et les cephalees primaires. Les opioides forts ont montre une efficacite moderee dans les DCNC de l’arthrose des membres inferieurs, des lombalgies et dans la douleur neuropathique. Leur introduction peut etre proposee uniquement apres l’echec des traitements de premiere intention associes a une prise en charge globale chez un patient informe des avantages et des risques. Il est deconseille de poursuivre le traitement des opioides forts au-dela de trois mois en l’absence d’amelioration de la douleur, de la fonction ou de la qualite de vie. Il est egalement recommande de ne pas prescrire des doses quotidiennes superieures a 150 mg d’equivalent morphine. Les facteurs de risque de mesusage doivent etre evalues avant l’introduction des opioides forts et le mesusage regulierement recherche en cours de traitement. La priorite doit etre donnee aux formes a liberation prolongee. Les formes de fentanyl transmuqueux a liberation immediate sont a proscrire dans les DCNC. Conclusion Ces recommandations s’adressent a tous les medecins amenes a prescrire des opioides forts dans la DCNC.

Background Neoangiogenesis is a crucial event to promote the development of the hyperplasic proliferative pathologic synovium in Rheumatoid arthritis (RA). Ultrasound (US) is sensitive for detection of power Doppler (PD) vascularisation. Objectives To explore the associations between a set of complementary circulating angiogenic markers reflecting different angiogenic processes and a comprehensive US assessment in patients with RA. Methods Serum levels of eight angiogenic markers (Vascular Endothelial Growth Factor (VEGF), Placenta Growth Factor (PlGF), Tie-2, Angiopoietin-1, soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), Interleukin-8 (IL-8, CXCL8), CYR61 (CCN1) and Angiostatin), reflecting endothelial cell activation, proliferation, survival, growth and migration, as well as vessel maturation and stabilisation, were measured by quantitative ELISAs in a total of 125 patients with RA, who were all systematically assessed in parallel by PDUS, performed on 32 joints. Results Synovitis was detected in 84 patients with RA (67.2%). Among these patients, 53 patients (42.4%) had positive Doppler signal, including 31 with moderate to marked hyperemia. Serum levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) (808±293 ng/mL vs. 697±240 ng/mL, p=0.022) and Tie-2 (16.2±7.5 ng/mL vs. 13.8±4.9 ng/mL, p=0.038), were more likely to be increased in patients with synovial hyperemia detected on at least one joint (Power Doppler grade ≥1). sVCAM-1, Tie-2 and Angiostatin concentrations gradually increased together with the grade of the semiquantitative PDUS scale (figure 1A-C) and concentrations of these three markers were markedly increased in patients with moderate to marked hyperemia (Power Doppler grade 2 and 3). Levels of sVCAM-1 (r=0.20, p=0.028), Tie-2 (r=0.28, p=0.001), and Angiostatin (r=0.25, p=0.006) correlated with a global arthritis sum score, defined by the sum of the semiquantitative PDUS scores for all joints examined. Among the 81 patients with a DAS28-CRP≤3.2, 22 patients had synovial hyperemia detected on at least one joint (Power Doppler grade 1 in 13 patients, grade 2 in 6 patients and grade 3 in 3 patients). Patients with synovial hyperemia on at least one joint were more likely to have significantly increased levels of PlGF (18.9±11.2 pg/mL vs. 13.1±9.5 pg/mL, p=0.022) and Tie-2 (15.7±5.8 ng/mL vs. 12.6±3.4 ng/mL, p=0.004) than patients with absence of synovial hyperemia. Conclusions Serum levels of the angiogenic markers Tie-2, sVCAM-1 and Angiostatin were strongly associated with synovial vascularisation and inflammation assessed by PDUS among patients with established RA. Moreover, Tie-2 and PlGF were associated with persistent disease activity in RA patients in mow disease activity. These findings suggest that it may possible to find surrogate serum angiogenic biomarkers of active synovitis that might replace PDUS examination, in case of further confirmation of their pertinence. Disclosure of Interest A. Leblond: None declared, S. Pezet: None declared, A. P. Trouvin: None declared, M. Elhai: None declared, V. Gonzalez: None declared, Y. Allanore Grant/research support from: Pfizer, J. Avouac: None declared

Introduction Physical therapy (PT) represents a major approach in musculoskeletal (MSK) pain. This study aimed to assess kinesiophobia, its impact and management, in patients with MSK pain treated by PT. Methods A national multicenter, prospective study was conducted in France in patients with MSK pain referred to PT. Kinesiophobia was scored with the Tampa Scale of Kinesiophobia (TSK). Pain, satisfaction, analgesic intake and acceptability were assessed at the initial visit, at the 5th PT session, and at the end of PT. Results A total of 700 consecutive outpatients with MSK pain, 54.5% female, referred to PT were recruited by 186 GPs: 501 had significant levels of kinesiophobia (TSK score > 40). Patients with kinesiophobia were significantly older, with less physical activity, more pain and less acceptability. Patients from GPs presenting with kinesiophobia had both higher pain and kinesiophobia levels. After 5 PT sessions, global satisfaction was significantly higher in patients without kinesiophobia. A significant increase of PT satisfaction was observed in patients who had been given preventive analgesics before PT sessions, in 25.6% of patients. Independent predictors for specific management of PT-induced pain were: patient's kinesiophobia (OR = 2.02 [1.07–3.82]), current analgesics treatment (OR = 2.05 [1.16–3.63]), GP with postgraduate course on pain (OR = 2.65 [1.29–5.43]), GP's independent practice (OR = 1.88 [1.01–3.48]). Conclusion Kinesiophobia is frequent in patients with MSK pain, is associated to GPs’ kinesiophobia and decreases satisfaction of physical therapy. Preventive analgesic treatment before PT sessions improves patients’ satisfaction and should be proposed to improve MSK pain management.

Background Neoangiogenesis is a crucial event to promote the development of the hyperplasic proliferative pathologic synovium in Rheumatoid arthritis (RA). Ultrasound (US) is sensitive for detection of power Doppler (PD) vascularization. Objective To explore the associations between a set of complementary circulating angiogenic markers and a comprehensive US assessment in patients with RA. Patients and methods Serum levels of eight angiogenic markers were measured by quantitative ELISAs in a total of 125 patients with RA, who were all systematically assessed in parallel by PDUS, performed on 32 joints. Results Serum levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and Tie-2 were more likely to be increased in patients with synovial hyperemia detected on at least one joint (Power Doppler grade ≥1). sVCAM-1, Tie-2 and Angiostatin concentrations gradually increased together with the grade of the semiquantitative PDUS scale and concentrations of these three markers were markedly increased in patients with moderate to marked hyperemia (Power Doppler grade 2 and 3). Levels of sVCAM-1, Tie-2, and Angiostatin correlated with a global arthritis sum score, defined by the sum of the semiquantitative PDUS scores for all joints examined. Levels of Tie-2 and Placenta Growth Factor (PlGF) were associated with PDUS features indicating residual disease activity. Conclusion Our results support the relevance of measuring serum levels of vascular markers to evaluate the intensity and extent of synovial vascularization. Angiogenic markers, and particularly Tie-2, could be a valuable surrogate of active synovitis and their place in relation to PDUS in clinical practice deserve further investigation.

Summary Our objective was to evaluate the contribution of monitoring B cell subset depletion after rituximab in patients with rheumatoid arthritis (RA) in order to guide reintroduction to forestall relapse. This prospective, monocentre study included all RA patients receiving two 1-g rituximab infusions at a 15-day interval. The patients were followed clinically and biologically every 2 months until rituximab reintroduction. The physician was blinded to lymphocyte-typing results to diagnose relapse and, hence, retreatment. Among the 39 patients included between March 2010 and December 2011 and followed until April 2013, seven received two rituximab cycles, yielding a total of 46 cycles for analysis. After the two rituximab cycles, the total number of CD19+ B cells decreased significantly (0·155 versus 0·0002 G/l, P < 0·0001), with complete depletions in all patients of CD19+ CD38++ CD24++ (transitional) (P < 0·0001) and CD19+ CD27+ (memory) B lymphocytes. A significant majority of patients relapsed within the 4 months following repopulation of total B (P = 0·036), B transitional (P = 0·007) and B memory (P = 0·01) lymphocytes. CD19+ B lymphocyte repopulation preceded clinical RA relapse and enabled its prediction 4 months in advance. Hence, monitoring of CD19+ B lymphocytes could serve as a tool to predict those relapses.

Pain is an ubiquitous symptom in osteoarticular diseases, occurring much more commonly than stiffness or disability. OA of the knee, hand, or hip affects around 20% of adults in various populations and is dramatically increasing in many countries, mostly related to age and obesity, leading to an increased number of people having OA pain, and creating a huge burden related to disability and health care costs. OA-related pain, has been classically considered to be a nociceptive pain condition. Clinicians have considered pain to be an alarm signal, correlated to the intensity of joint degradation. In OA, most authors have focused their studies on joint architecture and local degradation, considering pain as only a symptom, a consequence of joint damage. However, OA-related pain is a specific disease, with a complex pathophysiology, including neuropathic peripheral and central abnormalities, together with local inflammation involving all joint structures. Clinical findings emphasize that it is not a stable and linear condition, that pain experience is independent of structural modifications, and that the quality of pain in OA is important to consider, aside from its intensity. OA-related pain is modulated by many factors, including the individual patient's psychological and genetic factors, as well as the theoretical role of meteorological influences. Recent neuroimaging findings have improved our knowledge about central mechanisms of OA pain, especially in persistent cases.

Objectives Neurological manifestations seem common in primary Sjögren's syndrome (pSS) but their reported prevalences vary. We investigated the prevalence and epidemiology of neurological manifestations in a French nationwide multicentre prospective cohort of patients with pSS, the Assessment of Systemic Signs and Evolution in Sjögren's syndrome (ASSESS) cohort. Methods The ASSESS cohort, established in 2006, includes 395 patients fulfilling American–European Consensus Group criteria for pSS. Demographic and clinical data were compared between patient groups with and without neurological manifestations, and across patient groups with peripheral nervous system (PNS) manifestations, central nervous system (CNS) manifestations and no neurological manifestations. Results Data at inclusion were available for 392 patients, whose mean age was 58±12 years. Mean follow-up was 33.9 months. Neurological manifestations were present in 74/392 (18.9%) patients, including 63 (16%) with PNS manifestations and 14 (3.6%) with CNS manifestations. Prevalences were 9.2% for pure sensory neuropathy, 5.3% for sensorimotor neuropathy, 1.3% for cerebral vasculitis and 1.0% for myelitis. Neurological manifestations were associated with greater pSS activity as assessed using the ESSDAI (9.4±6.8 vs 4.3±4.8; p