Eating habits and the desire to eat healthier among patients with chronic pain: a registry-based study.

Healthcare professionals often meet pain patients with a poor nutritional status such as obesity, unhealthy dietary behaviors, and a suboptimal dietary intake. A poor nutritional status may play a significant role in the occurrence, development, and prognosis of chronic pain. This study investigated eating habits in a specialized pain rehabilitation center using data (N = 2152) from the Swedish quality registry for pain rehabilitation during the period 2016-2021. Patients answered a lifestyle questionnaire regarding their eating habits and desire to modify their lifestyle. The mean (SD) patient age was 46.1 (14.6) years, with 24.8% classified as obese. Suboptimal eating habits included irregular mealtimes (27.2%), weekly consumption of fast-food (20.3%) and nearly daily consumption of confectionery (33.3%). Approximately 20% (n = 426) reported a desire to eat healthier. Frequent confectionery intake (Odds ratio [OR] 1.23, 95% Confidence Interval (CI) 1.04-1.47) and fast-food consumption (OR 1.58, 95% CI 1.24-2.02) increased the likelihood to desire healthier eating. Younger patients (18-29 years), those classified as obese, and those with more extended spatial pain were more likely to express a desire to eat healthier. Eating habits should be addressed in pain management and interdisciplinary pain rehabilitation teams are encouraged to provide nutritional care tailored to the patient's needs.

Interdisciplinary pain rehabilitation for patients with Ehlers-Danlos syndrome and hypermobility spectrum disorders.

OBJECTIVE: Chronic pain is a common manifestation of Ehlers-Danlos syndrome and hypermobility spectrum disorders; thus it is often suggested that patients undergo generic interdisciplinary pain rehabilitation, despite there being little evidence to support this decision. The aim of this study is to examine the effectiveness of standard rehabilitation programmes for chronic pain on patients with Ehlers-Danlos syndrome and hypermobility spectrum disorders, compared with patients with other chronic pain disorders. SUBJECTS: Data, collected between 2008 and 2016, were extracted from a Swedish national registry. The patient data comprised of 406 cases with Ehlers-Danlos syndrome or hypermobility spectrum disorders, 784 cases with a whiplash-related diagnosis, 3713 cases with diagnoses relating to spinal pain, and 2880 cases of fibromyalgia. METHODS: The differences between groups on key outcome measures from pre- to 1-year follow-up after interdisciplinary pain rehabilitation were analysed using linear mixed effects models. Sensitivity analysis in the form of pattern-mixture modelling was conducted to discern the impact of missing data. RESULTS: No significant differences were found in improvements from pre- to 1-year follow-up for patients with Ehlers-Danlos syndrome or hypermobility spectrum disorder compared with other diagnostic groups regarding measures of health-related quality of life, mental health, or fatigue. At follow-up, differences in pain interference (d = -0.34 (95% confidence interval [95% CI] -0.5 to -0.18)), average pain (d = 0.22 (95% CI 0.11-0.62)) and physical functioning (d = 2.19 (95% CI 1.61-2.77)) were detected for the group with spinal-related diagnoses in relation to those with EDS/HSD, largely due to pre-treatment group differences. Sensitivity analysis found little evidence for missing data influencing the results. CONCLUSION: This study suggests that patients with Ehlers-Danlos syndrome/hypermobility spectrum disorders may benefit from inclusion in an interdisciplinary pain rehabilitation programme.

Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content.

Objectives: This explorative study analyses interrelationships between peripheral compounds in saliva, plasma, and muscles together with body composition variables in healthy subjects and in fibromyalgia patients (FM). There is a need to better understand the extent cytokines and chemokines are associated with body composition and which cytokines and chemokines differentiate FM from healthy controls. Methods: Here, 32 female FM patients and 30 age-matched female healthy controls underwent a clinical examination that included blood sample, saliva samples, and pain threshold tests. In addition, the subjects completed a health questionnaire. From these blood and saliva samples, a panel of 68 mainly cytokines and chemokines were determined. Microdialysis of trapezius and erector spinae muscles, phosphorus-31 magnetic resonance spectroscopy of erector spinae muscle, and whole-body magnetic resonance imaging for determination of body composition (BC)-i.e., muscle volume, fat content and infiltration-were also performed. Results: After standardizing BC measurements to remove the confounding effect of Body Mass Index, fat infiltration and content are generally increased, and fat-free muscle volume is decreased in FM. Mainly saliva proteins differentiated FM from controls. When including all investigated compounds and BC variables, fat infiltration and content variables were most important, followed by muscle compounds and cytokines and chemokines from saliva and plasma. Various plasma proteins correlated positively with pain intensity in FM and negatively with pain thresholds in all subjects taken together. A mix of increased plasma cytokines and chemokines correlated with an index covering fat infiltration and content in different tissues. When muscle compounds were included in the analysis, several of these were identified as the most important regressors, although many plasma and saliva proteins remained significant. Discussion: Peripheral factors were important for group differentiation between FM and controls. In saliva (but not plasma), cytokines and chemokines were significantly associated with group membership as saliva compounds were increased in FM. The importance of peripheral factors for group differentiation increased when muscle compounds and body composition variables were also included. Plasma proteins were important for pain intensity and sensitivity. Cytokines and chemokines mainly from plasma were also significantly and positively associated with a fat infiltration and content index. Conclusion: Our findings of associations between cytokines and chemokines and fat infiltration and content in different tissues confirm that inflammation and immune factors are secreted from adipose tissue. FM is clearly characterized by complex interactions between peripheral tissues and the peripheral and central nervous systems, including nociceptive, immune, and neuroendocrine processes.

Acceptance and Fear-Avoidance Mediate Outcomes of Interdisciplinary Pain Rehabilitation Programs at 12-Month Follow-Up: A Clinical Registry-Based Longitudinal Cohort Study from the Swedish Quality Registry for Pain Rehabilitation (SQRP).

Background: Factors that influence outcomes of interdisciplinary pain rehabilitation programs (IPRP) are poorly known. It is unclear how outcomes are influenced by pain intensity, psychological distress, and coping strategies. Aim: This clinical registry-based longitudinal cohort study has three aims: 1) to determine the relative importance of pain intensity, psychological distress, acceptance, and fear-avoidance for changes in three outcomes of IPRP at 12-month follow-up; 2) to investigate whether the effects of pain intensity and psychological distress on the three outcomes are mediated via acceptance and fear-avoidance; and 3) to determine whether sex is a moderator. Methods: This study uses Patient-Reported Outcome Measures (PROMs) from specialist units reporting data (2008-2016) to the Swedish Quality Registry for Pain Rehabilitation (SQRP). Adult chronic pain patients (N = 1991) answered the PROMs (background, pain, psychological distress, coping, participation, and health-related quality of life (HRQoL)). Partial Least Squares Structural Equation Modelling (PLS-SEM) was used to explore the aims. Results: Changes in acceptance (ß:0.424-0.553; all P<0.001) were the strongest predictor of the three outcomes (changes in life control, interference, and HRQoL) at 12-month follow-up. The next strongest predictor was baseline acceptance (ß: 0.177-0.233; all P<0.001) and changes in fear-avoidance (ß: -0.152- -0.186; all P<0.001). Baseline pain intensity and psychological distress showed weak positive associations. Their effects on the three outcomes were mediated via acceptance aspects. Sex was not a moderator. Discussion and Conclusion: Acceptance aspects (baseline and changes) were important predictors of IPRP outcomes. Changes in fear-avoidance were also important although to a lesser degree. Some of the effects of pain intensity and psychological distress on outcomes were mediated via acceptance at baseline. Future PLS-SEM analysis of real-world IPRP should include more potential mediators (eg, catastrophizing and more facets of psychological flexibility and fear-avoidance) and the components of IPRP.

Serum levels of endocannabinoids and related lipids in painful vs painless diabetic neuropathy: results from the Pain in Neuropathy Study.

ABSTRACT: N-arachidonoylethanolamine (also known as anandamide) and 2-arachidonoylglycerol are activators of the cannabinoid receptors. The endocannabinoid system also includes structurally and functionally related lipid mediators that do not target cannabinoid receptors, such as oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide. These bioactive lipids are involved in various physiological processes, including regulation of pain. The primary aim of the study was to analyze associations between serum levels of these lipids and pain in participants in the Pain in Neuropathy Study, an observational, cross-sectional, multicentre, research project in which diabetic patients with painless or painful neuropathy underwent deep phenotyping. Our hypothesis was that painful neuropathy would be associated with higher levels of the 5 lipids compared with painless neuropathy. Secondary aims were to analyze other patient-reported outcome measures and clinical data in relationship to lipid levels. The lipid mediators were analyzed in serum samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum levels of anandamide were significantly higher in the painful group, but the effect size was small (Cohen d = 0.31). Using cluster analysis of lipid data, patients were dichotomized into a "high-level" endocannabinoid group and a "low-level" group. In the high-level group, 61% of patients had painful neuropathy, compared with 45% in the low-level group ( P = 0.039). This work is of a correlative nature only, and the relevance of these findings to the search for analgesics targeting the endocannabinoid system needs to be determined in future studies.

Hurdles and potentials when implementing internet-delivered Acceptance and commitment therapy for chronic pain: a retrospective appraisal using the Quality implementation framework.

OBJECTIVES: Internet-delivered psychological interventions can be regarded as evidence-based practices and have been implemented in psychiatric and somatic care at primary and specialist levels. However, challenges as low adherence and poor routinization, have arisen during attempts to implement internet-delivered interventions in chronic pain settings. Internet-delivered Acceptance and Commitment Therapy (IACT) has been found to be helpful for chronic pain patients and might aid in developing pain rehabilitation services. However, the integration of IACT into standard health care has not yet been described from an implementation science perspective. The aim of this hybrid 1 effectiveness-implementation study was to evaluate the process of implementing IACT in a pain rehabilitation setting, to guide future implementation initiatives. METHODS: In this retrospective study we described actions taken during an implementation initiative, in which IACT was delivered as part of an interdisciplinary pain rehabilitation program (IPRP) at a specialist level clinic. All documents relevant to the study were reviewed and coded using the Quality Improvement Framework (QIF), focusing on adoption, appropriateness and sustainability. RESULTS: The QIF-analysis of implementation actions resulted in two categories: facilitators and challenges for implementation. Sustainability may be facilitated by sensitivity to the changing needs of a clinical setting and challenged by unfitting capacity building. Appropriateness might be challenged by an insufficient needs assessment and facilitated by aligning routines for communication with the clinic's existing infrastructure. Adoption may be facilitated by staff key champions and an ability to adapt to occurring hurdles. Possible influential factors, hypotheses and key process challenges are presented in a logic model to guide future initiatives. CONCLUSIONS: Sustainable implementation may depend on both the continuity of facilitating implementation actions and flexibility to the changing needs and interests of patients, caregivers and organization. We conclude that the use of theories, models and frameworks (TMF) as well as a logic model may ease design, planning and evaluation of an implementation process. Lastly, we suggest that IACT may be appropriate for IPRP when given before or after IPRP, focusing on psychiatric comorbidities.

Catastrophizing and acceptance are mediators between insomnia and pain intensity-an SQRP study of more than 6,400 patients with non-malignant chronic pain conditions.

Background: Sleep problems (insomnia) and chronic pain are associated. Chronic pain and insomnia/insufficient sleep quality share similar symptoms and features. Although they have a bidirectional relationship, more research is needed to understand how they interact via mediators and how moderators influence this relationship. Aims: In this large clinical registry-based cohort study (N = 6,497), we investigate important mediators between insomnia and pain intensity in a cross-sectional sample of chronic pain patients using advanced path analysis. In addition, we investigate whether some background variables were moderators of the identified important paths or not and the correlation patterns between insomnia and pain intensity in relation to the mediators. Methods: This study includes a cohort of adult patients with chronic non-cancer pain from the Swedish Quality Registry for Pain Rehabilitation (SQRP) with data on patient-reported outcome measures (PROMs) (2008-2016). The PROMs cover the background, pain aspects, psychological distress, pain-related cognitions, activity/participation, and health-related quality of life variables of the patients. Partial least squares structural equation modeling was used to explore the direct and indirect (via mediators) relationships between insomnia and pain intensity at baseline. Results: In this cohort study, insomnia was prevalent at 62.3%, and both direct and indirect mediating paths were present for the insomnia-pain intensity relationship. All of the mediating effects combined were weaker than the direct effect between insomnia and pain intensity. The mediating effects via catastrophizing and acceptance showed the strongest and equal mediating paths, and mediating effects via fear avoidance were the second strongest. Insomnia showed stronger direct significant correlations with psychological distress, catastrophizing, and acceptance compared with those of pain intensity. Sex, age, education level, spatial extent of pain, or body mass index did not moderate the mediating paths. Discussion and conclusion: This study confirms the existence of significant direct and mediating paths between reported insomnia and pain intensity. Future studies should focus on illuminating how sleep interventions influence pain intensity and other important key factors that contribute to the distress of chronic pain patients.

Cerebrospinal Fluid Metabolomics Identified Ongoing Analgesic Medication in Neuropathic Pain Patients.

BACKGROUND: Cerebrospinal fluid (CSF) can reasonably be hypothesized to mirror central nervous system pathophysiology in chronic pain conditions. Metabolites are small organic molecules with a low molecular weight. They are the downstream products of genes, transcripts and enzyme functions, and their levels can mirror diseased metabolic pathways. The aim of this metabolomic study was to compare the CSF of patients with chronic neuropathic pain (n = 16) to healthy controls (n = 12). METHODS: Nuclear magnetic resonance spectroscopy was used for analysis of the CSF metabolome. Multivariate data analysis by projection discriminant analysis (OPLS-DA) was used to separate information from noise and minimize the multiple testing problem. RESULTS: The significant OPLS-DA model identified 26 features out of 215 as important for group separation (R2 = 0.70, Q2 = 0.42, p = 0.017 by CV-ANOVA; 2 components). Twenty-one out of twenty-six features were statistically significant when comparing the two groups by univariate statistics and remained significant at a false discovery rate of 10%. For six out of the top ten metabolite features, the features were absent in all healthy controls. However, these features were related to medication, mainly acetaminophen (=paracetamol), and not to pathophysiological processes. CONCLUSION: CSF metabolomics was a sensitive method to detect ongoing analgesic medication, especially acetaminophen.

Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies.

OBJECTIVE: To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs). DESIGN: Umbrella review. DATA SOURCES: PubMed, PsychInfo, Embase, up to 9 February 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted. RESULTS: 101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive). CONCLUSIONS: Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events. STUDY REGISTRATION: PROSPERO CRD42018093045. FUNDING: None.

Effects of interdisciplinary pain rehabilitation programs on neuropathic and non-neuropathic chronic pain conditions - a registry-based cohort study from Swedish Quality Registry for Pain Rehabilitation (SQRP).

BACKGROUND AND AIM: Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. Pharmacological treatments for neuropathic pain often fail despite following guidelines. Interdisciplinary Pain Rehabilitation Programs (IPRP) are an effective intervention for chronic pain conditions. Little research has investigated whether IPRP can benefit patients with chronic neuropathic pain compared to other chronic pain conditions. This study assesses the real-world effects of IPRP on patients with chronic neuropathic pain compared to non-neuropathic patients using Patient-Reported Outcome Measures (PROMs) available in the Swedish Quality Registry for Pain Rehabilitation (SQRP). METHODS: A neuropathic group of patients (n = 1,654) were identified in two steps. This group was compared to a non-neuropathic group (n = 14,355) composed of common diagnoses (low back pain, fibromyalgia, whiplash associated disorders, and Ehlers-Danlos Syndrome) in relation to background variables, three overall outcome variables, and mandatory outcome variables (pain intensity, psychological distress symptoms, activity/participation aspects and health-related quality of life variables). Of these patients 43-44% participated in IPRP. RESULTS: At assessment, the neuropathic group reported significantly (with small effect sizes (ES)) more physician visits the previous year, older age, shorter pain durations, and less spatial extent of the pain (moderate ES). Moreover, for the 22 mandatory outcome variables, we found only clinically insignificant differences according to ESs between the groups. For patients participating in IPRP, the neuropathic group displayed equal or in some cases slightly superior results compared to the non-neuropathic group. DISCUSSION AND CONCLUSION: After assessing the real-world effects of IPRP, this large study found that neuropathic pain patients can benefit from the IPRP intervention. Both registry studies and RCTs are needed to better understand which patients with neuropathic pain are most suitable for IPRP and to what extent special considerations need to be made for these patients within the framework of IPRP.

Pain intensity and psychological distress show different associations with interference and lack of life control: A clinical registry-based cohort study of >40,000 chronic pain patients from SQRP.

Background: Both chronic pain and depressive and/or anxiety symptoms are associated with negative impacts on daily living, including interference and lack of life control. However, little is known about how pain and psychological distress affect these impacts. Aim: The first aim was to assess how pain intensity, psychological distress, and social support interact with interference and lack of life control. A second aim was to investigate whether the strength of these relationships is moderated by the presence or absence of depression and/or anxiety. Subjects and methods: Patient-Reported Outcome Measures (PROMs), which are available in the Swedish Quality Registry for Pain Rehabilitation (SQRP), were retrieved for patients with chronic pain (N = 40,184). A theoretical model with the constructs/latent variables pain intensity, psychological distress, interference, lack of life control, and social support was proposed and analyzed using Partial Least Squares Structural Equation Modelling (PLS-SEM). Indicators for these constructs were identified from the PROMs of the SQRP. Two models of the total cohort, which differed with respect to the causal relationship between pain intensity and psychological distress, were investigated. The moderating effects of anxiety and/or depression were also analyzed. Results: Relatively low correlation and explanatory power (R 2 = 0.16) were found for the pain intensity-psychological distress relationship. Pain intensity had a stronger effect on interference than on lack of life control. The reverse was found for psychological distress - i.e., psychological distress seemed to have a higher negative influence on function than on interference. The underlying assumption of the causal relationship between pain intensity and psychological distress determined how strong pain intensity and psychological distress influenced interference and lack of life control. Social support showed very similar absolute significant correlations with interference and lack of life control. Interference and lack of life control showed relatively weak associations. The psychological distress level was a moderating factor for several of the paths investigated. Discussion and conclusion: A clinical treatment consequence of the low correlation between pain intensity and psychological distress may be that clinically treating one may not reduce the effect of the other. The relative importance of pain intensity and psychological distress on interference and lack of life control depends on the underlying assumption concerning the pain intensity-psychological distress relationship. Interference and lack of life control showed relatively weak associations, underscoring the need to clinically assess them separately. Social support influenced both impact constructs investigated. The cohort display heterogeneity and thus presence of definite signs of anxiety and/or depression or not was a moderating factor for several of the associations (paths) investigated. The results are important both for the assessments and the design of treatments for patients with chronic pain.

Efficacy of mecobalamin (vitamin B12) in the treatment of long-term pain in women diagnosed with fibromyalgia: protocol for a randomised, placebo-controlled trial.

INTRODUCTION: Fibromyalgia causes long-term pain. It affects at least 2% of the population, the majority being women. In addition, extended symptoms corresponding to vitamin B12 deficiency occur. Findings from several studies have indicated that vitamin B12 may be a possible treatment for pain in fibromyalgia. The aim of the proposed study is to evaluate whether vitamin B12 decreases pain sensitivity and the experience of pain (ie, hyperalgesia and allodynia) in women with fibromyalgia. METHODS AND ANALYSIS: The study is a randomised, placebo-controlled, single-blind, clinical trial with two parallel groups which are administered mecobalamin (vitamin B12) or placebo over 12 weeks. 40 Swedish women aged 20-70 years with an earlier recorded diagnosis of fibromyalgia are randomised into the placebo group or the treatment group, each consisting of 20 participants. Outcomes consist of questionnaires measured at baseline and after 12 weeks of treatment. A final re-evaluation will then follow 12 weeks after treatment ends. The primary outcome is tolerance time, maximised to 3 min, which is assessed using the cold pressor test. In order to broaden the understanding of the lived experience of participants, qualitative interviews will be conducted using a phenomenological approach on a lifeworld theoretical basis (reflective lifeworld research approach). ETHICS AND DISSEMINATION: The protocol for the study is approved by the local ethical committee at Linkoping (EPM; 2018/294-31, appendices 2019-00347 and 2020-04482). The principles of the Helsinki Declaration are followed regarding oral and written consent to participate, confidentiality and the possibility to withdraw participation from the study at any time. The results will primarily be communicated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT05008042.

Work Interventions Within Interdisciplinary Pain Rehabilitation Programs (IPRP) - Frequency, Patient Characteristics, and Association with Self-Rated Work Ability.

Background: Interdisciplinary pain rehabilitation programs (IPRPs) help people with chronic pain improve their health and manage their work; however, the way IPRPs address sick leave could be improved. Although work interventions can be a part of IPRP, it is not well known how and to what extent. Aim: This study explores the frequency of work interventions and the characteristics of patients who participate in work interventions as part of IPRP at specialist pain rehabilitation departments in Sweden. In addition, this study explores the association between participation in work interventions and change in patients' self-rated work ability after IPRP. Methods: Data from the Swedish quality registry for pain rehabilitation (SQRP), which includes 3809 patients between 2016 and 2018, were analysed with descriptive statistics and regression analyses. Results: The results indicate a high participation rate in work interventions (90%). Some differences were evident concerning characteristics of patients who participated in different work interventions. The return-to-work (RTW) plan, the most frequently used work intervention, had the strongest association with change in self-rated work ability after IPRP. However, the effect sizes were small, and the initial score best explained the change. Furthermore, there were differences between employed and unemployed patients and employment had a positive association with change in self-rated work ability. Conclusion: More research is needed to understand IPRP's mechanisms and work interventions to support patients with chronic pain, reduce sick leave, and manage work. Employment status needs to be considered and interventions should be tailored to match the individual needs.

Fear network and pain extent: Interplays among psychological constructs related to the fear-avoidance model.

OBJECTIVE: Psychological constructs related to the fear-avoidance model such as fear of movement, pain catastrophizing, and affective distress have been found to be inter-related among patients with chronic pain. However, relationships of these constructs have mostly been examined using regression-based analyses. This cross-sectional study employs a novel analytical approach, network analysis, to illustrate the complex interplays among these variables as well as pain intensity and pain interference. METHODS: This study utilized the Swedish Quality Registry for Pain Rehabilitation, including data from 10,436 participants (76.0% women; Mage = 45.0 years). Networks were analyzed separately for patients with different pain extents (i.e., numbers of pain locations) as the interplays may differ qualitatively depending on pain extent. RESULTS: We found that patients with a larger pain extent showed a worse clinical presentation (i.e., more depression and anxiety, increased fear of movement and pain interference), and their network differed from the patients with a smaller number of pain extent in terms of how strongly key variables were interconnected. In all network models, pain interference and catastrophizing showed consistently influential roles. CONCLUSION: Our findings highlight the interactive nature of psychological aspects of pain and how interrelated associations differ depending on pain extent. Findings are discussed based on ideas on how both fear and pain become overgeneralized.

The effects of a 15-week physical exercise intervention on pain modulation in fibromyalgia: Increased pain-related processing within the cortico-striatal- occipital networks, but no improvement of exercise-induced hypoalgesia.

Dysfunctional top-down pain modulation is a hallmark of fibromyalgia (FM) and physical exercise is a cornerstone in FM treatment. The aim of this study was to explore the effects of a 15-week intervention of strengthening exercises, twice per week, supervised by a physiotherapist, on exercise-induced hypoalgesia (EIH) and cerebral pain processing in FM patients and healthy controls (HC). FM patients (n = 59) and HC (n = 39) who completed the exercise intervention as part of a multicenter study were examined at baseline and following the intervention. Following the exercise intervention, FM patients reported a reduction of pain intensity, fibromyalgia severity and depression. Reduced EIH was seen in FM patients compared to HC at baseline and no improvement of EIH was seen following the 15-week resistance exercise intervention in either group. Furthermore, a subsample (Stockholm site: FM n = 18; HC n = 19) was also examined with functional magnetic resonance imaging (fMRI) during subjectively calibrated thumbnail pressure pain stimulations at baseline and following intervention. A significant main effect of exercise (post > pre) was observed both in FM patients and HC, in pain-related brain activation within left dorsolateral prefrontal cortex and caudate, as well as increased functional connectivity between caudate and occipital lobe bordering cerebellum (driven by the FM patients). In conclusion, the results indicate that 15-week resistance exercise affect pain-related processing within the cortico-striatal-occipital networks (involved in motor control and cognition), rather than directly influencing top-down descending pain inhibition. In alignment with this, exercise-induced hypoalgesia remained unaltered.

The Vastus Lateralis Muscle Interstitium Proteome Changes after an Acute Nociception in Patients with Fibromyalgia Compared to Healthy Subjects-A Microdialysis Study.

Fibromyalgia (FM) is a complex disorder and a clinical challenge to diagnose and treat. Microdialysis is a valuable tool that has been used to investigate the interstitial proteins and metabolites of muscle in patients with fibromyalgia. The implantation of the catheter in the muscle causes acute tissue trauma and nociception. The aim of this study was to investigate acute proteome changes in the vastus lateralis muscle in women fibromyalgia patients (FM) and healthy subjects (CON). A further aim was to study if a 15-week resistance exercise program in FM had any influence on how chronic painful muscle responds to acute nociception. Twenty-six women patients with FM and twenty-eight CON were included in this study. A microdialysis catheter (100 kilo Dalton cut off, membrane 30 mm) was inserted in the vastus lateralis muscle, and samples were collected every 20 min. Subjects rated pain before catheter insertion, directly after, and every 20 min of sample collection. Dialysate samples from time points 0-120 were pooled and considered trauma samples due to the catheter insertion. The samples were analyzed with nano-liquid chromatography-tandem mass spectrometry (nLC-MS/MS). Advanced multivariate data analysis was used to investigate protein profile changes between the groups. Multivariate data analysis showed significant (CV-ANOVA p = 0.036) discrimination between FM and CON based on changes in 26 proteins. After the 15-week exercise intervention, the expression levels of the 15 proteins involved in muscle contraction, response to stimulus, stress, and immune system were increased to the same expression levels as in CON. In conclusion, this study shows that microdialysis, in combination with proteomics, can provide new insights into the interstitial proteome in the muscle of FM. In response to acute nociception, exercise may alter the innate reactivity in FM. Exercise may also modulate peripheral muscle proteins related to muscle contraction, stress, and immune response in patients with FM.

Patients' Expectations Before Initiation of Intrathecal Baclofen Treatment: A Longitudinal Study with 1-Year Follow-Up.

OBJECTIVE: To investigate patients' expectations, met/unmet expectations and satisfaction with intrathecal baclofen treatment in relation to effect on spasticity, pain intensity, sleep quality, occupational performance, well-being and self-efficacy. DESIGN: A prospective longitudinal study with follow-up at 1 year. PATIENTS: Consecutive patients, age ≥ 18 years with a disabling spasticity of cerebral or spinal origin selected for intrathecal baclofen treatment at 2 university hospitals in Sweden were included. From August 2016 to June 2019, 35 patients began intrathecal baclofen treatment; 29 patients were included and completed the study. METHODS: Baseline and 1-year follow-up included assessment of spasticity by physiotherapists, a semi-structured interview regarding occupational performance using the Canadian Occupational Performance Measure and a questionnaire. RESULTS: Overall satisfaction with treatment and satisfaction with occupational performance were reported as moderate. Important variables that explained satisfaction with occupational performance were improvements in performance, expectations and performance before treatment. Patients had higher expectations compared with the 1-year outcomes regarding occupational performance, spasticity, pain intensity and sleep quality, although improvements were reported. CONCLUSION: A thorough discussion of goal setting with intrathecal baclofen treatment before implantation is necessary to give patients individual and realistic expectations.

Burden of disease and management of osteoarthritis and chronic low back pain: healthcare utilization and sick leave in Sweden, Norway, Finland and Denmark (BISCUITS): study design and patient characteristics of a real world data study.

OBJECTIVES: Osteoarthritis (OA) and chronic low back pain (CLBP) are common musculoskeletal disorders with substantial patient and societal burden. Nordic administrative registers offer a unique opportunity to study the impact of these conditions in the real-world setting. The Burden of Disease and Management of Osteoarthritis and Chronic Low Back Pain: Health Care Utilization and Sick Leave in Sweden, Norway, Finland and Denmark (BISCUITS) study was designed to study disease prevalence and the societal and economic burden in broad OA and CLBP populations. METHODS: Patients in Sweden, Norway, Finland and Denmark with diagnoses of OA or CLBP (low back pain record plus ≥2 pain relief prescriptions to indicate chronicity) were identified in specialty care, in primary care (Sweden and Finland) and in a quality-of-care register (Sweden). Matched controls were identified for the specialty care cohort. Longitudinal data were extracted on prevalence, treatment patterns, patient-reported outcomes, social and economic burden. RESULTS: Almost 1.4 million patients with OA and 0.4 million with CLBP were identified in specialty care, corresponding to a prevalence in the Nordic countries of 6.3 and 1.9%, respectively. The prevalence increased to 11-14% for OA and almost 6% for CLBP when adding patients identified in primary care. OA patients had a higher Elixhauser comorbidity index (0.66 vs. 0.46) and were using opioids (44.7 vs. 10.2%) or long-term nonsteroidal anti-inflammatory drug (NSAIDs) (20.9 vs. 4.5%) more than four times as often as compared to controls. The differences were even larger for CLBP patients compared to their controls (comorbidity index 0.89 vs. 0.39, opioid use 77.7 vs. 9.4%, and long-term NSAID use 37.2 vs. 4.8%). CONCLUSIONS: The BISCUITS study offers an unprecedented, longitudinal healthcare data source to quantify the real-world burden of more than 1.8 million patients with OA or CLBP across four countries. In subsequent papers we aim to explore among others additional outcomes and subgroups of patients, primarily those patients who may benefit most from better healthcare management.

An investigation of metabolome in blood in patients with chronic peripheral, posttraumatic/postsurgical neuropathic pain.

Neuropathic pain (NP) is a chronic pain condition resulting from a lesion or disease in the somatosensory nervous system. The aim of this study was to investigate the metabolome in plasma from patients with chronic peripheral, posttraumatic/postsurgical NP compared to healthy controls. Further, we aimed to investigate the correlation between pain intensity and the metabolome in plasma. The metabolic profile in plasma samples from 16 patients with chronic NP and 12 healthy controls was analyzed using a nuclear magnetic resonance spectroscopy method. Information about pain intensity, pain duration, body mass index (BMI), age, sex, and blood pressure were obtained through a questionnaire and clinical examination. Multivariate data analysis was used to identify metabolites significant for group separation and their correlation with pain intensity and duration, BMI, and age. We found 50 out of 326 features in plasma significantly contributing to group discrimination between NP and controls. Several of the metabolites that significantly differed were involved in inflammatory processes, while others were important for central nervous system functioning and neural signaling. There was no correlation between pain intensity and levels of metabolite in NP. These findings indicate that there seems to be peripheral/systemic differences in the metabolic profile between patients with chronic NP and healthy individuals.