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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 IPRPs 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., Funding Agencies|Swedish Research Council for Health, Working Life and Welfare [FORTE: 2016-07414]

Objective: Psychological constructs related to the fear-avoidance model such as fear of movement, pain cata-strophizing, and affective distress have been found to be inter-related among patients with chronic pain. How-ever, 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., Funding Agencies|AFA insurance; Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; [DNR 190054]; [2015-02512]; [2017-00177]

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.

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 respons

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 am

Background: Obesity is a risk factor for the development of fibromyalgia (FM) and generally most studies report increased Body Mass Index (BMI) in FM. Obesity in FM is associated with a worse clinical presentation. FM patients have low physical conditioning and obesity further exacerbates these aspects. Hitherto studies of FM have focused upon a surrogate for overall measure of fat content, ie, BMI. This study is motivated by that ectopic fat and adipose tissues are rarely investigated in FM including their relationships to physical capacity variables. Moreover, their relationships to clinical variables including are not known. Aims were to 1) compare body composition between FM and healthy controls and 2) investigate if significant associations exist between body composition and physical capacity aspects and important clinical variables.Methods: FM patients (n = 32) and healthy controls (CON; n = 30) underwent a clinical examination that included pressure pain thresholds and physical tests. They completed a health questionnaire and participated in whole-body magnetic resonance imaging (MRI) to determine body composition aspects.Results: Abdominal adipose tissues, muscle fat, and BMI were significantly higher in FM, whereas muscle volumes of quadriceps were smaller. Physical capacity variables correlated negatively with body composition variables in FM. Both body composition and physical capacity variables were significant regressors of group belonging; the physical capacity variables alone showed stronger relationships with group membership. A mix of body composition variables and physical capacity variables were significant regressors of pain intensity and impact in FM. Body composition variables were the strongest regressors of blood pressures, which were increased in FM.Conclusion: Obesity has a negative influence on FM symptomatology and increases the risk for other serious conditions. Hence, obesity, dietary habits, and physical activity should be considered w, Funding Agencies|Swedish Research Council [2018-02470]

Background: There is considerable diversity of outcome selections and methodologies for handling the multiple outcomes across all systematic reviews (SRs) of Interdisciplinary Pain Treatment (IPT) due to the complexity. This diversity presents difficulties for healthcare decision makers. Better recommendations about how to select outcomes in SRs (with or without meta-analysis) are needed to explicitly demonstrate the effectiveness of IPT.Objective: This overview systematically collates the reported outcomes and measurements of IPT across published SRs and identifies the methodological characteristics. Additionally, we provide some suggestions on framing the selection of outcomes and on conducting SRs of IPT.Methods: Three electronic databases (PubMed, Cochrane Library, and Epistemonikos) and the PROSPERO registry for ongoing SR were supplemented with hand-searching ending on 30 September 2021. Results: We included 18 SRs with data on 49007 people from 356 primary randomised controlled trials (RCTs); eight were followed by meta-analysis and ten used narrative syntheses of data. For all the SRs, pain was the most common reported outcome (72%), followed by disability/functional status (61%) and working status (61%). Psychological well-being and quality of life were also reported in half of the included SR (50%). The core outcome domains according to VAPAIN, IMMPACT, and PROMIS were seldom met. The methodological quality varied from critically low to moderate according to AMSTAR2. The AMSTAR2 rating was negatively correlated to the number of outcome domains in PROMIS, and VAPAIN was positively correlated with IMMPACT and PROMIS, indicating the intercorrelations between the reported outcomes. Conclusion: This systematic overview showed wide-ranging disparity in reported outcomes and applied outcome domains in SRs evaluating IPT interventions for chronic pain conditions. The intercorrelations between the reported outcomes should be appropriately handled in future research, Funding Agencies|County Council of Ostergotland, Sweden

Background: Patients with chronic pain often experience insomnia symptoms. Pain initiates, maintains, and exacerbates insomnia symptoms, and vice versa, indicating a complex situation with an additional burden for these patients. Hence, the evaluation of insomnia-related interventions for patients with chronic pain is important. Objective: This randomized controlled trial examined the effectiveness of internet-based cognitive behavioral therapy for insomnia (ICBT-i) for reducing insomnia severity and other sleep- and pain-related parameters in patients with chronic pain. Participants were recruited from the Swedish Quality Registry for Pain Rehabilitation. Methods: We included 54 patients (mean age 49.3, SD 12.3 years) who were randomly assigned to the ICBT-i condition and 24 to an active control condition (applied relaxation). Both treatment conditions were delivered via the internet. The Insomnia Severity Index (ISI), a sleep diary, and a battery of anxiety, depression, and pain-related parameter measurements were assessed at baseline, after treatment, and at a 6-month follow-up (only ISI, anxiety, depression, and pain-related parameters). For the ISI and sleep diary, we also recorded weekly measurements during the 5-week treatment. Negative effects were also monitored and reported. Results: Results showed a significant immediate interaction effect (time by treatment) on the ISI and other sleep parameters, namely, sleep efficiency, sleep onset latency, early morning awakenings, and wake time after sleep onset. Participants in the applied relaxation group reported no significant immediate improvements, but both groups exhibited a time effect for anxiety and depression at the 6-month follow-up. No significant improvements on pain-related parameters were found. At the 6-month follow-up, both the ICBT-i and applied relaxation groups had similar sleep parameters. For both treatment arms, increased stress was the most frequently reported negative effect. Conclusions: In

Mechanism-based diagnosis and therapies for chronic pain are lacking. However, bio-psycho-social interventions such as interdisciplinary multimodal rehabilitation programs (IPRPs) have shown to be relatively effective treatments. In this context we aim to investigate the effects of IPRP on the changes in levels of bioactive lipids and telomerase activity in plasma, and if these changes are associated with changes in pain intensity and psychological distress. This exploratory study involves 18 patients with complex chronic pain participating in an IPRP. Self-reports of pain, psychological distress, physical activity, and blood samples were collected before the IPRP and at a six-month follow-up. Levels of arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA), oleoylethanolamide (OEA), stearoylethanolamide (SEA), and telomerase activity were measured. Pain intensity was decreased, and SEA levels were increased at the six-month follow up. A significant correlation existed between changes in SEA levels and pain intensity. AEA levels, were inversely correlated with physical activity. Furthermore, 2-AG and telomerase activity was significantly correlated at the six-month follow-up. This study confirms that IPRP is relatively effective for reduction in chronic pain. Changes in SEA were correlated with changes in pain intensity, which might indicate that SEA changes reflect the pain reduction effects of IPRP., Funding Agencies|Swedish Research Council, Region Oestergoetland (Stiftelsefoervaltningen, Research-ALF)Swedish Research Council; Magnus Bergvalls foundation; ake Wiberg foundation

Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www. coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via nonprobability/snowball and representative sampling and assessed via self-rating and parental rating. Nonmodifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COHFIT project, with representative samples from eleven countries. Limitations: Cross-sectional and anonymous design. Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on childrens, adolescents and families, mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.

Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/ functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. Results: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of >= 1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged >= 65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. Limitations: . Cross-sectional survey, preponderance of non-representative participants. Conclusions: . Results from COH-FIT will comprehensively quantify the impact

One in five diabetic patients suffers from chronic pain with neuropathic characteristics, but the pathophysiological mechanisms underlying the development of neuropathic pain in diabetic distal symmetrical polyneuropathy (DSP) patients are poorly understood. Systemic low-grade inflammation has been implicated, but there is still a considerable knowledge gap concerning its scope and meaning in this context. The aim of the study was to establish the broad inflammatory signature of painful diabetic DSP in serum samples from the Pain in Neuropathy Study (PiNS), an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the present two-cohorts exploration-replication study (180 participants in each cohort), serum samples from PiNS participants were analyzed with the Olink INFLAMMATION panel (Olink Bioscience, Uppsala, Sweden) which enables the simultaneous measurement of 92 inflammation-related proteins (mainly cytokines, chemokines and growth factors). In both the exploration and the replication cohort, we identified a high-inflammation subgroup where 14 inflammation-related proteins in particular were associated with more neuropathy and higher pain intensity. The top 3 proteins were HGF, CSF-1 and CD40 in both cohorts. In the exploratory cohort, additional clinical data were available, showing an association of inflammation with insomnia and self-reported psychological distress. Hence, this cross-sectional exploration-replication study seems to confirm that low-grade systemic inflammation is related to the severity of neuropathy and neuropathic pain in a subgroup of diabetic DSP patients. The pathophysiological relevance of these proteins for the development of neuropathic pain in diabetic DSP patients must be explored in more depth in future studies.

IntroductionAbout 20% of the adult population have chronic pain, often associated with psychological distress, sick leave and poor health. There are large variations in the clinical picture. A biopsychosocial approach is used in investigation and treatment. The concept of personalised medicine, that is, optimising medication types and dosages for individual patients based on biomarkers and other patient-related factors, has received increasing attention in different diseases but used less in chronic pain. This cooperative project from all Swedish University Hospitals will investigate whether there are changes in inflammation and metabolism patterns in saliva and blood in chronic pain patients and whether the changes correlate with clinical characteristics and rehabilitation outcomes.Methods and analysisPatients at multidisciplinary pain centres at University Hospitals in Sweden who have chosen to participate in the Swedish Quality Registry for Pain Rehabilitation and healthy sex-matched and age-matched individuals will be included in the study. Saliva and blood samples will be collected in addition to questionnaire data obtained from the register. From the samples, proteins, lipids, metabolites and micro-RNA will be analysed in relation to, for example, diagnosis, pain characteristics, psychological distress, body weight, pharmacological treatment and clinical rehabilitation results using advanced multivariate data analysis and bioinformatics.Ethics and disseminationThe study is approved by the Swedish Ethical Review Authority (Dnr 2021-04929) and will be conducted in accordance with the declaration of Helsinki.The results will be published in open access scientific journals and in popular scientific relevant journals such as those from patient organisations. Data will be also presented in scientific meetings, meeting with healthcare organisations and disseminated in different lecturers at the clinics and universities., Funding Agencies|Petrus and Augusta Hedlunds Foundation; Gun and Bertil Stohnes Foundation; Loo and Hans Osterman Foundation; Demens foundation; Brain foundation [FO2018-0315]; Senil demens Sarfond foundation Region Orebro; Gamla Tjanarinnor foundation; Swedish Research Council [2018-02470]; Research-ALF region Ostergotland [RO-834951]

Background: Although neuropathic pain is a significant problem in polyneuropathy, the underlying molecular mechanisms are poorly understood. The endogenous bioactive lipids 2-arachidonoyl-glycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) are known to influence pain and inflammation in the peripheral nervous system. The aim of this study was to explore the plasma levels of endocannabinoids and related lipids and health-related quality of life in patients with polyneuropathy with and without pain. Methods: Patients (n = 48) with Chronic Idiopathic Axonal Neuropathy were included. Clinical data were retrieved from medical files. All patients filled out the SF-36 and EQ-5D questionnaires. In addition, blood samples were analyzed for 2-AG, OEA, PEA, and SEA. Results: Neuropathic pain was reported in 21 of the patients. There were significantly lower levels of 2-AG in patients with neuropathic pain (P = 0.03), but there were no significant differences in OEA (P = 0.61), PEA (P = 0.95), or SEA (P = 0.97) levels. The patients reporting pain in the hands had significantly lower SEA levels, 10.0 versus 15.0 (P = 0.03). The levels of 2-AG were significantly higher among patients reporting paresthesia in their feet (80.1 vs. 56.3; P = 0.02). Levels of PEA, SEA, and 2-AG were decreased in patients with loss of vibration. PEA and SEA were decreased in patients with loss of pain and temperature, and SEA decreased in patients with loss of sense of touch. However, the differences in the levels of bioactive endogenous lipids were not statistically significant when corrected for multiple comparisons. Conclusion: Alterations of 2-AG levels between polyneuropathy patients with and without neurogenic pain indicate that it could play an essential role. Further studies are warranted.

Objective: The concept of "invalidation" refers to the patients perception that the social environment does not recognize their medical condition. This study explores and describes invalidation experiences among Swedish patients with chronic widespread pain with regard to sociodemographic and pain characteristics, impact of pain, self-reported health, and symptoms of anxiety and depressive. Methods: A cross-sectional design using questionnaires, including sociodemographic and pain variables, the Illness Invalidation Inventory (Likert scale items regarding 5 sources), the Hospital Anxiety and Depression Scale, and the Short-Form General Health Survey. Descriptive and univariate analyses were applied. Results: Of the 152 respondents, 91% were women. Swedish patients with chronic widespread pain experienced invalidation to a large extent from all sources. The highest scores for invalidation were reported from contacts with social services (68%), and the lowest from spouses (30%). Being younger (p < 0.006), having periodic pain (p = 0.011), and having had more frequent visits to a doctor in the previous year (p = 0.007) were characteristics associated with higher invalidation scores. Experiences of invalidation were associated with worse self-reported mental health scores (r = -0.29 to -0.46). Conclusion: Since patients with chronic widespread pain frequently experience invalidation from the social environment, this further challenge in daily life must be taken into consideration in pain management within multimodal pain rehabilitation., Funding Agencies|AFA Insurance and forskningsALF (County Council of Ostergotland)

Objective: To explore the associations between habitual self-reported physical activity, pain sensitivity and patient-reported outcomes (including pain intensity) in patients with chronic pain. Design: Cross-sectional, experimental study. Subjects: Patients (n = 78), age range 18-65 years, with different chronic pain conditions (> 3 months) were compared with age- and sex-matched healthy controls (n = 98). Methods: Multivariate correlations between selfreported physical activity, pressure pain sensitivity, and patient-reported outcome measures were assessed. Results: Lower perceived health status (p <0.001, Cohens d =2.34), higher levels of depression (p< 0.001, Cohens d = 1.77), and lower pain tolerance threshold (p < 0.001, Cohens d = 1.66) were the most prominent variables discriminating patients from controls. In patients, bivariate and multivariate analyses showed that higher pressure pain tolerance was associated with male sex, lower pain intensity and fewer painful regions, higher self-efficacy and more self-reported physical activity, but not with lower levels of anxiety and depression. Conclusion: Pain tolerance thresholds, as well as degree of depression and perceived health status discriminated between patients and controls, and there was an association between pain tolerance thresholds and level of self-reported physical activity in patients. This study highlights the importance of further research into how increased physical activity may improve pain sensitivity in patients with chronic pain., Funding Agencies|ALF Research Grants Region Ostergotland; Research grant, Sinnescentrum, Region Ostergotland; Danish National Research Foundation [DNRF121]

Purpose: Quantitative sensory testing (QST) can be applied to quantify the sensitivity to different painful stimuli. This study aims to evaluate the association between preoperative pressure and thermal pain thresholds and trajectories of measurements of postoperative recovery (patient-reported daily maximum and average pain intensity, sum score of symptoms, and analgesic consumption) after benign hysterectomy.Patients and Methods: A prospective, longitudinal single-blinded, observational multicenter study was conducted in five hospitals in the southeast of Sweden between 2011 and 2017. A total of 406 women scheduled for abdominal or vaginal hysterectomy for benign conditions were enrolled in the study. QST measuring pressure (PPT), heat (HPT), and cold pain thresholds (CPT) were performed preoperatively. The cut-off levels for dichotomizing the pain thresholds (low/high) were set at the 25-percentile for PPT and HPT and the 75-percentile for CPT. The Swedish Postoperative Symptom Questionnaire was used to measure postoperative pain and other symptoms of discomfort (symptom sum score) on 13 occasions for six weeks postoperatively. Daily analgesic consumption of opioids and non-opioids was registered.Results: A CPT above the 75-percentile was associated with high postoperative maximum pain intensity (p = 0.04), high symptom sum score (p = 0.03) and greater consumption of non-opioids (p = 0.03). A HPT below the 25-percentile was only associated with greater consumption of non-opioids (p = 0.02). PPT was not associated with any of the outcome measures.Conclusion: CPT seemed to be predictive for postoperative pain and symptoms of discomfort after benign hysterectomy. Preoperative QST may be used to individualize the management of postoperative recovery for low pain threshold individuals., Funding Agencies|Medical Research Council of Southeast Sweden [FORSS-228581, FORSS-308471, FORSS-387681, FORSS-482051]; Region OEstergoetland Council (ALF grants) [ROE-200641, ROE-276871, ROE-35651, ROE-448391, ROE-540551, ROE-607891, ROE-699021, ROE-794531, ROE-931528, ROE-936208, ROE-968764]; Linkoeping University; Danish National Research Foundation [DNRF121]

Introduction: Little is still known about the underlying mechanisms that drive and maintain neuropathic pain (NeuP). Recently, lipids have been implicated as endogenous proalgesic ligands affecting onset and maintenance of pain; however, in the case of NeuP, the relationship is largely unexplored. Objectives: The aim of this study was to investigate the lipoprotein profile in patients with chronic peripheral NeuP compared with healthy controls. Methods: The concentrations of 112 lipoprotein fractions in plasma from patients with NeuP (n = 16) and healthy controls (n = 13) were analyzed using proton nuclear magnetic resonance spectroscopy. A multiplex immunoassay based on an electrochemiluminescent detection method was used to measure the concentration of 71 cytokines in plasma from patients with NeuP (n = 10) and healthy controls (n = 11). Multivariate data analysis was used to identify patterns of protein intercorrelations and proteins significant for group discrimination. Results: We found 23 lipoproteins that were significantly upregulated in patients with NeuP compared with healthy controls. When the influence of cytokines was included in a regression model, 30 proteins (8 cytokines and 22 lipoprotein fractions) were significantly upregulated or downregulated in patients with NeuP. Both conditions presented lipoprotein profiles consistent with inflammation. Body mass index did not affect lipoprotein profiles in either group. No relationship between age and lipoprotein pattern was found in NeuP, but a significant relationship was found in healthy controls. Conclusion: Patients with NeuP presented a lipoprotein profile consistent with systemic low-grade inflammation, like that seen in autoimmune, cardiometabolic, and neuroprogressive diseases. These preliminary results emphasize the importance of chronic low-grade inflammation in NeuP., Funding Agencies|Swedish Research Council; ALF Research Grants; Region Ostergotland; NEURO Sweden