Audun Stubhaug

• Vingen, Hans Vangsnes; Ćuk, Ana; Sauter, Axel Rudolf; Spigset, Olav; Andersen, Finn Husøy & Skedsmo, Fredrik [Vis alle 11 forfattere av denne artikkelen] (2026). Prolonging peripheral ropivacaine nerve block with an in situ-formed hydrogel carrier: randomized controlled trial in an ovine model. Regional anesthesia and pain medicine. ISSN 1098-7339. doi: 10.1136/rapm-2026-108092. Fulltekst i vitenarkiv Vis sammendrag

  Background Local anesthetics are effective for regional anesthesia but have a relatively short duration of action. This motivates the development of sustained-release delivery systems. The aim of this study was to evaluate whether an in situ-forming hydrogel composed of poloxamers and alginate could prolong the duration of ropivacaine-induced sensory and motor blockade. Methods In this randomized and blinded two-period cross-over study, 10 female sheep received ultrasound-guided sciatic nerve injections of either 200 mg ropivacaine poloxamer-alginate hydrogel (Rop-HG) or 200 mg, as a control, plain ropivacaine solution (Rop-C). Sensory and motor functions were assessed repeatedly using a standardized clinical scoring system. Plasma ropivacaine concentrations were measured over time, and postmortem histopathological evaluation of the sciatic nerve and surrounding tissues was performed. Results Rop-HG markedly prolonged block duration compared with Rop-C, increasing the median (IQR) sensory block from 24 hours (IQR 16–36) to 60 hours (IQR 60–72) and the median motor block from 16 hours (IQR 16–18) to 60 hours (IQR 36–72). Pharmacokinetic analysis showed a sharp early peak for Rop-C (median C max 5101 nmol/L and median T max 0.33 hours), whereas Rop-HG produced a lower and delayed profile (median C max 558 nmol/L and median T max  8 hours). Histopathology revealed more pronounced and persistent local tissue reactions in Rop-HG-treated limbs, characterized by degeneration, necrosis, and inflammation. Conclusion Ultrasound-guided perineural injections of 200 mg Rop-HG substantially prolonged the clinical duration of sciatic nerve block and reduced early systemic exposure compared with a 200 mg plain ropivacaine solution. However, the formulation was associated with severe local tissue degeneration, necrosis, and inflammation. Consequently, it remains unclear whether the prolonged clinical effect resulted from a sustained pharmacological release of ropivacaine or from the local tissue toxicity. Further optimization of the formulation is required before clinical translation.

• Nes, Lise Solberg; Børøsund, Elin; Nordang, Elise Flakk; Asbjørnsen, Rikke Aune; Eide, Hilde & Varsi, Cecilie [Vis alle 15 forfattere av denne artikkelen] (2026). Delivery Model Matters for Digital Interventions in Pain Self-Management: Mixed Methods Study. Journal of Medical Internet Research (JMIR). ISSN 1439-4456. 28. doi: 10.2196/89780. Fulltekst i vitenarkiv
• Azulay, Naomi; Singstad, Bjørn-Jostein; Schirmer, Henrik; Løchen, Maja-Lisa; Olsen, Roy Bjørkholt & Jenssen, Trond [Vis alle 10 forfattere av denne artikkelen] (2026). Exploring hemodynamic measurements from the Tromsø Study for prediction of cardiovascular disease using traditional statistical models and machine learning approaches. Scientific Reports. doi: 10.1038/s41598-026-57003-5. Fulltekst i vitenarkiv Vis sammendrag

  Abstract In Norway, NORRISK2 is the government-recommended risk model for predicting an individual’s 10-year probability of getting cardiovascular disease (CVD). This study aims to investigate the potential for improvement of CVD prediction by using hemodynamic measurements from a non-invasive beat-to-beat blood pressure monitor, taken as part of pain sensitivity assessment with the cold-pressor test (CPT) during the Tromsø6 Study (2007–2008). Using 6694 recordings, ultra-short-term pulse rate variability (PRV) and baroreflex sensitivity (BRS) obtained during the CPT were added as additional variables into the existing NORRISK2 survival model (extended model). In addition, the time-series data was used in a machine learning (ML) model without the NORRISK2 background variables. Both models were compared to a recalibration of the original NORRISK2 model. The predictions from the recalibrated NORRISK2 model and the ML model were then combined with logistic regression. The statistical models performed similarly on the test set, with an area under the receiver operating characteristic (AUROC) of 0.8 (95% CI: 0.71–0.86), 0.79 (0.71–0.85) and 0.77 (0.69–0.84) (original, recalibrated and extended NORRISK2, respectively). The ML model using only hemodynamic measurements obtained a test set AUROC of 0.73 (0.67–0.80). Combining the NORRISK2 and ML model did not increase the AUROC. Adding ultra-short-term PRV and BRS derived from Tromsø6 did not improve the prediction of the NORRISK2 model either. Although with lower accuracy, the beat-to-beat time series of hemodynamic variables from a CPT had a significant (p < 0.01) ability to predict future CVD without any other person-specific data.

• Bollemeijer, Juliette; Page, Christian Magnus; Klein, Isabel; Danielsen, Kjersti; Furberg, Anne-Sofie & Jenssen, Marita [Vis alle 13 forfattere av denne artikkelen] (2026). Chronic Pain and Pain Tolerance in Psoriasis: A Cross-sectional Study of Three Population-based Cohorts in the Netherlands and Norway. Acta Dermato-Venereologica. ISSN 0001-5555. 106. doi: 10.2340/actadv.v106.adv-2026-0510. Fulltekst i vitenarkiv Vis sammendrag

  Pain is increasingly recognized as an important butunder-addressed symptom in psoriasis. Although oftenattributed to psoriatic arthritis (PsA) or skin-relatedpain, individuals with psoriasis or PsA also reportpain in other musculoskeletal structures, including axialand buttock pain (1, 2). Quantitative sensory testing(QST) uses standardized experimental stimuli to assesspain thresholds and tolerance, and small studies inpsoriasis or PsA have reported reduced pressure painthresholds (3, 4). However, large population-basedstudies assessing chronic pain and QST measures inpsoriasis, both with and without PsA, are lacking,despite the substantial impact of pain in psoriasis onhealth-related quality of life (5). Using data from threelarge population-based cohorts in the Netherlands andNorway, we therefore examined whether individualswith psoriasis differ from controls in chronic pain,number of pain sites, pain intensity and pain toleranceassessed by 2 QST measures: the cold pressor test(CPT) and cuff pressure algometry (PAlg). We alsoevaluated the influence of PsA, psoriasis activity andseverity on these associations.

• Eikeseth, Fillip Ferreira; Pedersen, Geir; Stubhaug, Audun; Sütterlin, Stefan & Kvarstein, Gunnvald (2026). Psychometric evaluation of the Level of Personality Functioning Scale - Brief Form 2.0 in adults with chronic pain. Scandinavian Journal of Pain. ISSN 1877-8860. 26(1). doi: 10.1515/sjpain-2025-0037. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Chronic pain and personality disorders frequently co-occur. This co-occurrence may pose challenges in pain management and should be addressed by clinicians to optimize outcomes. The Level of Personality Functioning Scale – Brief Form 2.0 (LPFS-BF) is a time-efficient screening tool for impairments in personality functioning based on the Alternative DSM-5 Model for Personality Disorders. Methods This cross-sectional study evaluates the psychometric properties of the LPFS-BF in a sample of adults with chronic pain. Data was retrieved from the Oslo University Hospital Pain Registry and includes 892 participants referred to outpatient pain management. The psychometric properties of the LPFS-BF were investigated in terms of factor structure, scale reliability, and concurrent validity with anxiety and depression, health-related quality of life, and past week usual pain intensity. Results Mean age was 49 years and 64 % were female. A bifactor structure showed best model fit: Comparative fit index=0.995, Tucker-Lewis index=0.993, root mean square error of approximation=0.023, standardized root mean square residual=0.030. Scale reliability was good for the general factor (ω t =0.89, ω h =0.79), poor for the self domain (ω t =0.25, ω h =0.05), and questionable for the interpersonal domain (ω t =0.68, ω h =0.40). Explained common variance for the general factor was 68 % which supported essential unidimensionality. The magnitudes of the associations between the LPFS-BF and the investigated variables were comparable to previous research, thus supporting its concurrent validity. Conclusions The results suggest that the LPFS-BF is best viewed as a unidimensional scale in the current sample and support the LPFS-BF as a valid and reliable screening tool for impairments in personality functioning among individuals with chronic pain.

• Pogatzki-Zahn, Esther M.; Lucia, Sarah De; Weinmann, Claudia; Heitkamp, Hauke; Hummelshoj, Lone & Liedgens, Hiltrud [Vis alle 42 forfattere av denne artikkelen] (2025). A core outcome set of measurement instruments for assessing effectiveness and efficacy of perioperative pain management: results of the international IMI-PainCare PROMPT Delphi consensus process. British Journal of Anaesthesia. ISSN 0007-0912. 134(5), s. 1460–1473. doi: 10.1016/j.bja.2025.01.029. Fulltekst i vitenarkiv Vis sammendrag

  Background Effective perioperative pain management is crucial to prevent patient suffering, delayed recovery, chronic postsurgical pain, and long-term opioid use. However, the heterogeneous use of outcomes in studies complicates evidence synthesis and might not accurately reflect the experiences of individual patients. We initiated a consensus process to establish a core outcome set (COS) of patient-reported outcome measures (PROMs) in postoperative pain, building upon the earlier consensus on a COS of domains. Methods Potential PROMs were identified via systematic literature searches for the domains pain intensity (with subdomains at rest and during activity), physical function, self-efficacy, and adverse events, followed by appraisal of psychometric properties according to the COnsensus-based Standards for the selection of health Measurement INstruments methodology. Then, a consensus meeting was convened, followed by a Delphi process with an international, multiprofessional panel of stakeholders, including those with lived experience. A conclusive consensus meeting approved the final COS of PROMs. Results The final COS consists of one unidimensional numerical rating scale for assessing pain intensity on average, worst pain intensity, pain intensity at rest, and procedure-specific pain intensity during activity; one unidimensional scale for pain interfering with activities in bed; one procedure-specific scale for assessing physical function; the IMI-PainCare PROMPT adaptation of the Arthritis Self-Efficacy Scale for assessing self-efficacy; and the IMI-PainCare PROMPT adaptation of the Opioid-Related Symptom Distress Scale for assessing adverse events. Conclusions Comprehensive use of a core outcome set will help harmonise outcome assessment, facilitate comparisons between studies, promote patient-centred research, and improve postoperative pain care.

• Ekholdt, Christopher; Granan, Lars-Petter Ness; LUNDELAND, BÅRD; Stubhaug, Audun & Meier, Kaare (2025). The neuromodulation registry survey: A web-based survey to identify and describe characteristics of European medical patient registries for neuromodulation therapies in chronic pain treatment. Scandinavian Journal of Pain. ISSN 1877-8860. 25(1). doi: 10.1515/sjpain-2025-0025. Fulltekst i vitenarkiv Vis sammendrag

  Objectives This survey aims to identify and describe the characteristics of registries for neuromodulation implantations used to treat chronic pain in Europe. Neuromodulation therapies such as spinal cord stimulation (SCS) are employed to treat chronic pain through implantable medical devices. These therapies are considered effective and are part of standard care in many countries. Registries can provide valuable real-world data to complement randomized controlled clinical trials. Materials and methods We conducted a web-based survey to gather information on registries monitoring neuromodulation implants for chronic pain treatment, and the survey was sent to 101 European centers. Results We received responses from 47 centers across 17 European countries. Of these, 27 centers reported using a registry for neuromodulation therapies to treat pain, which this study is based upon. National registries exist in Belgium, the Netherlands, the UK, as well as a national registry solution in France. Non-national registries were identified in Denmark, Finland, Norway, Spain, Sweden, Switzerland, and Turkey. We present an overview on data types collected from different registries. Categories of variables collected are quite consistent across registries and are mostly in line with recommendations for chronic pain. The primary objective of the registries is most commonly measuring clinical outcomes and complications, while guideline adherence is less commonly monitored. The most frequently reported challenge is the lack of personnel for planning, designing, and funding for running the registries. Conclusions We identified 27 centers utilizing neuromodulation registries for chronic pain treatment, with 23 providing detailed data. Although the survey’s limitation is its findings are not generalizable to all registries, the findings offer key insights for the establishment and growth of registries in neuromodulation. Registries primarily aim to investigate the clinical and patient-reported outcomes, though variability in other clinical data collection remains a challenge for benchmarking and guideline adherence. Significant financial and organizational hurdles exist, which can be addressed through cooperative initiatives.

• Nordrik, Torbjørn; Rotevatn, Elisabeth Ørskov; Mannseth, Janne; Stubhaug, Audun & Rygh, Lars Jørgen (2025). Opioid use at admittance increases need for intrahospital specialized pain service: Evidence from a registry-based study in four Norwegian university hospitals. Scandinavian Journal of Pain. ISSN 1877-8860. 25(1). doi: 10.1515/sjpain-2025-0008. Fulltekst i vitenarkiv Vis sammendrag

  Objectives: Acute Pain Services (APS) have significantly evolved since their establishment in the 1990s, emphasizing multimodal analgesia, which is a pivotal component of enhanced recovery after surgery, to enhance postoperative recovery. Despite improvements, variability in pain trajectories among patients necessitated the development of transitional pain units to address individual needs and ensure safe opioid tapering. The Norwegian National Registry for Advanced Acute Pain Services (AAPS), known as SmerteReg, was established to further enhance understanding of pain treatment in these patients. In this study, we aimed to analyze opioid use patterns and characteristics of opioid users referred to AAPS compared to non-opioid users. Methods: Data from SmerteReg (2016–2020) were analyzed, including patient demographics, diagnoses, pain treatment, and patient-reported outcome measures. Patient characteristics at admittance were compared between opioid users and non-opioid users. Multivariate logistic regression was used to explore factors associated with opioid use. Results: Of 1,068 patient tracks, 64% were opioid users at admittance. Opioid users were older and more frequently female, reporting higher levels of anxiety, depression, catastrophizing, and sleep problems before admission. Sleep problems before admittance was reported three times more frequent by patients using opioids compared to patients not using an opioid at admittance. Conclusion: Pre-admittance opioid use was prevalent among patients referred to AAPS, emphasizing the need for tailored pain management strategies. Women, older patients, and those reporting sleep problems before admittance were more likely to use opioids. The finding that sleep problems before admittance were strongly associated with opioid use, suggests the importance of addressing sleep disturbances in pain management protocols. This study contributes to understanding opioid use patterns and factors influencing pain management in hospitalized patients.

• Jensen, Amalie Storaa; Steingrímsdóttir, Ólöf Anna; Jönsson, Birgitta; Stubhaug, Audun; Nielsen, Christopher Sivert & Hadler-Olsen, Elin (2025). Orofacial Pain Is Associated With Oral Health–Related Quality of Life: The Tromsø Study 2015-2016. International Dental Journal. ISSN 0020-6539. 76(1). doi: 10.1016/j.identj.2025.109328. Fulltekst i vitenarkiv
• Årnes, Anders Pedersen; Fjeld, Mats Kirkeby; Morseth, Bente; Hopstock, Laila Arnesdatter; Horsch, Alexander & Wilsgaard, Tom [Vis alle 10 forfattere av denne artikkelen] (2025). Exploring the Relationship Between Physical Activity and Pressure Pain Tolerance in the General Population. The Tromsø Study 2015–2016. European Journal of Pain. ISSN 1090-3801. 30(1). doi: 10.1002/ejp.70187. Fulltekst i vitenarkiv Vis sammendrag

  Background Physical activity (PA) is commonly recommended for the treatment and prevention of pain. Several small‐sample studies have indicated a relationship between PA and pressure pain sensitivity. Methods This study used data from the seventh Tromsø Study (2015–2016) cohort to assess how questionnaire‐based leisure time PA (LTPA), occupational PA (OPA), and exercise‐expended metabolic equivalent of task (MET) hours per week ( n  = 21,083), as well as accelerometer‐measured total counts and moderate‐to‐vigorous PA (MVPA; n  = 6778) relate to pressure pain tolerance (PTol). Flexible parametric survival analysis was used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Results Higher LTPA and MET‐hours per week were associated with higher levels of PTol ( p  < 0.001). With sedentary LTPA as a reference group, results indicated a HR of 0.87 (95% CI: 0.83, 0.92) for light, 0.75 (0.71, 0.80) for moderate, and 0.63 (0.53, 0.73) for vigorous PA. Compared to < 7.5 MET‐hours per week, HRs were 0.92 (0.88, 0.96) for 7.5–14.9 MET‐hours per week, 0.84 (0.78, 0.89) for 15–22.5 MET‐hours per week, and 0.86 (0.82, 0.91) for > 22.5 MET‐hours per week. A similar pattern was observed for accelerometer‐measured PA, with a HR of 0.91 (0.88, 0.95) for MVPA and 0.93 (0.90, 0.96) for total activity counts. No clear pattern was observed for OPA. Interaction analysis indicated generally stronger effects for men, but no differences across age groups. Conclusion The findings suggest that higher PA in leisure‐time contexts is associated with higher pain tolerance levels in the general population. Significance Statement Higher physical activity levels are linked to increased pressure pain tolerance, highlighting its role in modulating pain. Notably, only leisure‐time activity shows a beneficial effect, while occupational activity does not. These findings suggest that the type and combination of activity may uniquely influence pain perception, challenging the idea that all physical activity benefits pain equally. Since physical activity is widely used in clinical pain management, this distinction has key implications for tailoring exercise‐based interventions to optimize outcomes.

• Nermo, Hege; Petrenya, Natalia; Steingrímsdóttir, Ólöf Anna; Stubhaug, Audun; Nielsen, Christopher Sivert & Hadler-Olsen, Elin Synnøve (2025). Experimental pain tolerance is associated with dental anxiety– the Tromsø study 2015–2016. BMC Oral Health. 25. doi: 10.1186/s12903-025-06441-0. Fulltekst i vitenarkiv Vis sammendrag

  Background There are individual differences in pain sensitivity. Dental anxiety may increase the experience of pain during dental treatment, and painful dental treatments may trigger or amplify dental anxiety. This study aimed to explore if experimental pain tolerance in extremities, measured outside the setting of dental treatment, was associated with dental anxiety. Methods This cross-sectional study included participants from the seventh survey of the population based Tromsø Study with data on dental anxiety ( n  = 20 186, 40–99 years old, 52.4% women). Dental anxiety was assessed by the Modified Dental Anxiety Scale (MDAS). Tolerance to two experimental pain modalities was evaluated. Pressure pain tolerance (PPT) was measured by computerized cuff pressure on the leg as pressure endured up to a maximum of 100 kPa. Cold-pressor tolerance (CPT) was recorded as time to withdrawal of hand from circulating cold water to a maximum of 120 s. MDAS score across cohort characteristics was assessed with descriptive analyses. The association between pain tolerance and dental anxiety was assessed using binary negative binomial and multinomial logistic regressions adjusted for age, sex, personal finances, smoking, emotional distress, persistent pain, general-, and dental health. Results The median MDAS score was 6 (25-percentile: 5, 75-percentile: 9) and the mean was 7.7 (standard deviation: 3.8). Lower experimental pain tolerance was positively associated with MDAS score in fully adjusted models, with p-values for tests of linear trend < 0.001 for both PPT and CPT. Compared to not aborting the test, aborting PPT prior to 48.43 kPa and CPT before 25 s (cut-offs for the lowest tertile among those who aborted the tests) was associated with a 12% and 8% increase in MDAS score, respectively ( p  < 0.001). Multinomial logistic regressions showed that the association between experimental pain tolerance and MDAS scores was most pronounced in the highest MDAS category (≥ 19). Conclusions Although causality cannot be interpreted from this cross-sectional study, our findings suggests that a generalized low pain tolerance may render a person more vulnerable for development of dental anxiety. Dentists should have knowledge of and respect individual differences in pain tolerance and strive for optimal pain management in dental settings.

• Strand, Elin Bolle; Varsi, Cecilie; Børøsund, Elin; Eide, Hilde; Schreurs, Karlein M. G. & Waxenberg, Lori B. [Vis alle 12 forfattere av denne artikkelen] (2025). Changes in cognition, coping, pain and emotions after 12-months access to the digital self-management program EPIO. Frontiers in Psychology. 16. doi: 10.3389/fpsyg.2025.1540852. Fulltekst i vitenarkiv Vis sammendrag

  Background: Psychosocial pain self-management interventions can be of support for people living with chronic pain. Since psychosocial support is not always accessible, digital health interventions may increase outreach of these types of evidence-based interventions. Objectives: To explore participants' experiences from 12-month access to the digital pain self-management program EPIO, particularly in terms of any behavioral and/or psychological changes experienced. Methods: Participants (N = 25) engaged in individual semi-structured interviews following 12-month access to the EPIO intervention. Qualitative thematic analyses were conducted seeking to identify any behavioral and/or psychological changes experienced through intervention use, and what contributed to these changes. Results: Participants were predominantly women (72%), median age 46 (range 26–70), with a range of self-reported pain conditions and the majority reporting pain duration >10 years (64%). Analyses identified three main themes and subsequent sub-themes: (1) Changes in Cognition; insight and self-awareness, acceptance and shifting focus, (2) Changes in Coping; pain, emotions, and activity pacing, and (3) Content and Functionality Specific Engagement; breathing and other mind-body exercises, thought-reflection exercises, and functionalities. Conclusions: People with chronic pain experienced positive behavioral and/or psychological changes in terms of cognition and coping after 12 months access to the EPIO digital pain self-management program. The most prominent changes included increased understanding of the connection between own thoughts, feelings, and behavior, gaining concrete strategies to cope with everyday life living with pain, and utilizing these strategies to reduce pain and interference of pain, as well as to improve emotion regulation and psychological wellbeing.

• Zerouga, Insaf; Valeur, Jørgen; Sommer, Christine; Carlsen, Monica Hauger; Hagen, Milada & Høivik, Marte Lie [Vis alle 22 forfattere av denne artikkelen] (2025). Habitual Intake of Macronutrients and Fermentable Oligo-, Di-, Monosaccharides and Polyols is not associated with Irritable Bowel Syndrome-like Symptoms in Inflammatory Bowel Disease. Clinical Nutrition ESPEN. ISSN 2405-4577. 67, s. 105–113. doi: 10.1016/j.clnesp.2025.03.005. Fulltekst i vitenarkiv
• Samuelsen, Per-Jostein; Hjellvik, Vidar; Odsbu, Ingvild; Stubhaug, Audun; Skurtveit, Svetlana Ondrasova & Vambheim, Sara Magelssen (2025). Trends in Postoperative Opioid Use in Norway 2011-2018: A Nationwide Registry-Based Study. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 136(6). doi: 10.1111/bcpt.70040. Fulltekst i vitenarkiv Vis sammendrag

  Little is known about the overall trends in postoperative opioid use in a Nordic setting. We investigated the trends in Norway between 2011 and 2018. We linked the Norwegian Prescription Database, the Norwegian Patient Registry, the Cancer Registry of Norway and the Cause of Death Registry. Postoperative opioid use was defined as the first opioid dispensing per year within 14 days of a NOMESCO Classification of Surgical Procedure code. We excluded patients with cancer or opioid maintenance therapy. We calculated period prevalence (Norwegian population ≥ 15 years as the denominator), substance distribution, initial amount and proportion of long-acting formulations. Among 746 435 postoperative opioid users ≥ 15 years, the period prevalence increased from 27.0/1000 in 2011 to 30.0/1000 in 2018 (long-term use: 2.0 to 3.3/1000). Codeine was most frequent (67%) in 2011, while codeine and tramadol were equally dispensed (41% and 43%) in 2018; oxycodone increased from 3% to 12%. The initial amount increased for opioids as a group but declined for oxycodone (1236 morphine milligram equivalents [MME]/patient to 914 MME/patient) and tramadol (233 MME/patient to 219 MME/patient). Long-acting depot formulations increased from 5% to 12%. Over time, postoperative opioid use increased, with a shift toward more tramadol and oxycodone in lower initial amounts, and increased use of long-acting formulations.

• Lund, Charlotte Indre; Rosseland, Leiv Arne; Steingrímsdóttir, Ólöf Anna; Engdahl, Bo Lars; Stubhaug, Audun & Furberg, Anne-Sofie [Vis alle 7 forfattere av denne artikkelen] (2024). How is age at menopause and reproductive lifespan associated with chronic pain outcomes in postmenopausal women? Pain. ISSN 0304-3959. 166(1), s. 144–152. doi: 10.1097/j.pain.0000000000003333. Fulltekst i vitenarkiv Vis sammendrag

  Female sex is a prominent risk factor for chronic pain, although the underlying mechanisms are not fully understood. This cross-sectional study aimed to investigate the relationship between age at menopause, reproductive lifespan, and chronic pain in a sample of postmenopausal women aged 40 to 93 years. Data were collected from the Tromsø study conducted in Norway between 2015 and 2016 (Tromsø7). Chronic pain was assessed using a single question, which formed a sample size of 5741 participants. Chronic widespread pain was evaluated using the more comprehensive Graphical Index of Pain, resulting in a sample size of 5920 women. Premenopausal women and those who experienced menstrual cessation due to chemotherapy/radiation or hormonal intrauterine devices were excluded from the analysis. Adjusted relative risk ratios with 95% confidence intervals were calculated to determine associations. The results showed that early menopause was associated with a 1% increase in the prevalence of chronic pain for each year of

• Årnes, Anders; Fjeld, Mats Kirkeby; Stigum, Hein; Nielsen, Christopher Sivert; Stubhaug, Audun & Johansen, Aslak [Vis alle 10 forfattere av denne artikkelen] (2024). Does pain tolerance mediate the effect of physical activity on chronic pain in the general population? the Tromsø Study. Pain. ISSN 0304-3959. 165(9), s. 2011–2023. doi: 10.1097/j.pain.0000000000003209. Fulltekst i vitenarkiv
• Farnes, Nadine; Granan, Lars-Petter Ness; Jacobsen, Henrik Børsting; Stubhaug, Audun & vambheim, Sara Magelssen (2024). Associations of long-term clinical recovery and improved quality of life across ICD-11 chronic pain categories in a real-world registry study. European Journal of Pain. ISSN 1090-3801. doi: 10.1002/ejp.2250. Fulltekst i vitenarkiv Vis sammendrag

  Background There is little knowledge of what factors are needed for successful chronic pain management. We aim to identify psychosocial and treatment predictors of clinical recovery and improved quality of life (QOL) at 12-month follow-up across three chronic pain groups, based on the International Classification of Diseases-11: neuropathic pain, secondary non-neuropathic pain, and primary pain. Furthermore, we investigate baseline differences across diagnostic groups. Methods The sample included baseline and 12-month follow-up data from 1056 chronic pain patients from the Oslo University Hospital's Pain Registry. Logistic regression models investigated longitudinal associations between psychosocial and treatment characteristics, and the outcome measures clinical recovery and improved QOL. Characteristics were compared across the diagnostic groups. Results Increased odds of clinical recovery and improved QOL were seen in patients receiving invasive treatment (OR = 8.04, 95% CI = 3.50–19.40; OR = 5.47, 95% CI = 2.42–12.86), while decreased odds of clinical recovery were seen for secondary non-neuropathic pain patients with pain-related disability (0.05, 95% CI = 0.01–0.29). In comparing baseline characteristics, neuropathic pain patients had lower QOL, and more severe insomnia compared to the other groups. Conclusion Invasive treatment modalities were strongly associated with clinical recovery and improved QOL. Although this could be due to patient selection, it does warrant further examination as an intervention alternative for chronic pain. Intervention efficacy, risk factors and predictors of clinical recovery across diagnostic groups should be further investigated through longitudinal RCTs. Significance This observational study indicates a potential advantage in sustained recovery for pre-selected individuals with chronic pain who undergo invasive treatments. The relationship between sustained recovery and psychosocial factors differs across neuropathic, secondary non-neuropathic, and primary pain patients. This suggests that employing ICD-11 for classifying patients into mechanistically distinct pain groups could inform the evaluation and management of chronic pain. Furthermore, factors previously identified as negative indicators for long-term outcomes in chronic pain cohorts were not clinically significant in this study.

• Eikeseth, Fillip Ferreira; Pedersen, Geir; Hummelen, Benjamin; Sütterlin, Stefan; Stubhaug, Audun & Kvarstein, Elfrida Hartveit [Vis alle 7 forfattere av denne artikkelen] (2024). Pain prevalence rates and the mediating role of negative affect in adults referred to personality disorder treatment: A cross-sectional study. Journal of Pain. ISSN 1526-5900. 26. doi: 10.1016/j.jpain.2024.104724. Fulltekst i vitenarkiv Vis sammendrag

  Personality disorders (PDs) are prevalent among individuals with chronic pain, but less is known about the prevalence of pain in the PD population. This study therefore sought to explore the prevalence of current or everyday pain among individuals referred to outpatient PD treatment, and further explore the mediating role of negative affect in the relationship between PD severity and current pain. Data was retrieved from the Norwegian Network for PDs’ quality register which included 4361 participants. Pain was operationalized using the EQ-5D-3L “pain or discomfort” item and four SCL-90-R pain-related items (“pain bothersomeness”). Rates of self-reported pain were explored both pre and post treatment to determine the persistency of the pain-related symptoms. The role of negative affect in the relationship between PD severity and pain was investigated by linear regression analysis. A substantial burden of pain-related symptoms was demonstrated, as 71 % and 80 % reported moderate to extreme pain or discomfort and pain bothersomeness, respectively. Muscle soreness was the most common pain (59 %) followed by headache (48 %), low back pain (46 %), and heart or chest pain (34 %). Moderate to extreme pain or discomfort was persistent for 77 % of the participants who provided end of treatment data (mean treatment duration was 82 weeks). Negative affect mediated the relationship between PD severity and pain. To our knowledge, this is the first large-scale study on everyday pain in patients with PDs. The findings reveal that moderate to extreme pain is prevalent among persons with PDs and that this co-occurrence is driven by negative affect.

• Farnes, Nadine; Jacobsen, Henrik Børsting; Stubhaug, Audun & vambheim, Sara Magelssen (2024). H-coil repetitive transcranial magnetic stimulation does not improve executive function in patients with chronic peripheral neuropathic pain: a randomized sham-controlled crossover study. Frontiers in Psychiatry. 15. doi: 10.3389/fpsyt.2024.1401008. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Deep rTMS is an increasingly popular noninvasive brain stimulation technique which has shown promise for treating cognitive impairments. However, few studies have investigated the cognitive effects it could exert in patients with chronic peripheral neuropathic pain. Therefore, we aimed to assess the effects of deep rTMS on executive functioning in patients with peripheral neuropathic pain, in a randomized, double-blind crossover trial. Methods: In total, 17 patients were randomly assigned to receive both active and sham deep H-coil rTMS targeting the primary motor cortex. Each treatment period consisted of five daily rTMS sessions. Selected tests of executive functioning from the CANTAB test battery (paired associates learning, stop signal task, spatial working memory and multitasking test) were performed at baseline, and at 1 week and 3 weeks follow-ups. Results: We did not find any significant interactions between time and treatment for the measures of executive functioning for the patient group, or for patients with reduced cognition compared to normative means. Conclusion: High-frequency deep H-coil rTMS targeting the hand area of the primary motor cortex and delivered over 5 consecutive days did not improve executive functioning in patients with chronic peripheral neuropathic pain. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05488808.

• Hadler-Olsen, Elin Synnøve; Petrenya, Natalia; Jönsson, Birgitta; Steingrímsdóttir, Ólöf Anna; Stubhaug, Audun & Nielsen, Christopher Sivert (2024). Periodontitis is associated with decreased experimental pressure pain tolerance: The Tromsø Study 2015–2016. Journal of Clinical Periodontology. ISSN 0303-6979. 51(7), s. 874–883. doi: 10.1111/jcpe.13968. Fulltekst i vitenarkiv Vis sammendrag

  Aim - To assess the relationship between periodontitis and experimental pain tolerance.<p> <p>Materials and Methods - Participants from the population-based seventh survey of the Tromsø Study with data on periodontitis were included (n = 3666, 40–84 years old, 51.6% women). Pain tolerance was assessed through (i) pressure pain tolerance (PPT) test with a computerized cuff pressure algometry on the leg, and (ii) cold-pressor tolerance (CPT) test where one hand was placed in circulating 3°C water. Cox proportional hazard regression was used to assess the association between periodontitis and pain tolerance adjusted for age, sex, education, smoking and obesity.<p> <p>Results - In the fully adjusted model using the 2012 Centers for Disease Control/American Academy of Periodntology case definitions for surveillance of periodontitis, moderate (hazard ratio [HR] = 1.09; 95% confidence interval [CI]: 1.01, 1.18) and severe (HR = 1.25, 95% CI: 1.11, 1.42) periodontitis were associated with decreased PPT. Using the 2018 classification of periodontitis, having Stage II/III/IV periodontitis was significantly associated with decreased PPT (HR = 1.09; 95% CI: 1.01, 1.18) compared with having no or stage I periodontitis. There were no significant associations between periodontitis and CPT in fully adjusted models.<p> <p>Conclusions - Moderate and severe periodontitis was associated with experimental PPT.

• Berg, Kristin Sandal; Seines, Ellisiv; Gâl, Petter; Løberg-Emanuelsen, Lise; Stubhaug, Audun & Nielsen, Erik Waage [Vis alle 7 forfattere av denne artikkelen] (2024). Absorption and pharmacokinetics of bupivacaine after bilateral topical administration in tonsillar fossae for posttonsillectomy pain relief. Pharmacology Research & Perspectives. 12(2). doi: 10.1002/prp2.1196. Fulltekst i vitenarkiv Vis sammendrag

  No previous studies have investigated the systemic absorption of bupivacaine when used topically for posttonsillectomy pain. The present study was undertaken to investigate the pharmacokinetics of bupivacaine after administration by a swab in the tonsillar fossae over 4 min after tonsillectomy. Eleven adult patients undergoing elective tonsillectomy were recruited. After removal of both tonsils, each of the two tonsillar fossae was covered with a swab moistened with 2 mL of bupivacaine 5 mg/mL, that is, a total of 20 mg bupivacaine. Blood samples were drawn after 0, 5, 10, 20, 30, 45, and 60 min. Bupivacaine was analyzed with an ultra-high-performance liquid chromatography–tandem mass spectrometry method. The highest single measured bupivacaine serum concentration was 23.2 ng/mL and took place 10 min after drug administration. Mean (±SD) Cmax was 11.4 ± 6.0 ng/mL and mean tmax was 11.3 ± 4.7 min. Mean t1/2 was 31.6 ± 9.3 min. As the toxic concentration threshold has been reported to be in the interval 1500–4500 ng/mL, the concentrations measured were well below 2% of the lowest cited toxic threshold. In conclusion, this study shows that applying 4 mL of bupivacaine 5 mg/mL by a swab in the tonsillar fossae posttonsillectomy yields very low plasma concentrations, suggesting its safe application without any risk of systemic toxic effects.

• Fjeld, Mats Kirkeby; Årnes, Anders Pedersen; Engdahl, Bo Lars; Morseth, Bente; Hopstock, Laila Arnesdatter & Horsch, Ludwig Alexander [Vis alle 12 forfattere av denne artikkelen] (2024). The physical activity paradox; exploring the relationship with pain outcomes. The Tromsø Study 2015-2016. Pain. ISSN 0304-3959. 166(2), s. 315–327. doi: 10.1097/j.pain.0000000000003344. Fulltekst i vitenarkiv Vis sammendrag

  Paradoxical associations have been observed for leisure-time physical activity (LTPA) and occupational physical activity (OPA) and several health-related outcomes. Typically, higher LTPA is associated with health benefits and high OPA with health hazards. Using data from the Tromsø Study (2015-2016), we assessed how questionnaire-based LTPA and OPA (n = 21,083) and accelerometer-measured physical activity (PA) (n = 6778) relate to pain outcomes. Leisure-time physical activity and OPA were categorized as inactive PA, low PA, and moderate-to-vigorous PA and then aggregated into 9 levels, eg, inactive LTPA/inactive OPA. Accelerometer-measured PA included counts/minute, steps/day, and WHO PA recommendations from 2010 to 2020. Three binary pain outcomes (any pain, any chronic pain, and moderate-to-severe chronic pain) were constructed based on pain location, intensity, duration, and impact on daily activities. By using Poisson regression to estimate absolute and relative associations, we found that high LTPA was associated with lower pain prevalence and vice versa for OPA. Compared to inactive LTPA, prevalence ratio (PR) with 95% confidence intervals was lowest for moderate-to-vigorous LTPA, 0.93 (0.89-0.96) for any pain, 0.88 (0.84-0.93) for any chronic pain, and 0.66 (0.59-0.75) for moderate-to-severe chronic pain. Compared to sedentary OPA, the ratio was highest for moderate-to-vigorous OPA, 1.04 (1.01-1.07) for any pain, 1.06 (1.02-1.10) for any chronic pain, and 1.33 (1.21-1.46) for moderate-to-severe chronic pain. Aggregated LTPA and OPA showed lower outcomes for moderate-to-vigorous LTPA combined with lower levels of OPA. Higher levels of accelerometer-measured PA were associated with less pain. To summarize, we found inverse associations for LTPA and OPA. Benefits from LTPA seem to depend on low levels of OPA.

• Vambheim, Sara Magelssen; Hjellvik, Vidar; Odsbu, Ingvild; Skurtveit, Svetlana Ondrasova; Ekholdt, Christopher & Granan, Lars-Petter Ness [Vis alle 8 forfattere av denne artikkelen] (2024). Postoperative opioid use in Norway-a population-based observational study on patterns of long-term use. BMC Pharmacology and Toxicology. 25(1), s. 1–9. doi: 10.1186/s40360-024-00805-y. Fulltekst i vitenarkiv Vis sammendrag

  Background The utilization patterns of opioid analgesics and the proportion of long-term opioid use after surgery in Norway is largely unknown. Methods This study aimed to estimate the proportion of one-year long-term prescription opioid use among all Norwegian postoperative opioid users. Complete data from central health registries (NPR, NorPD, Statistics Norway, CoDR) were linked via the personal identification number unique to all citizens. The study period was January 1st 2010 until December 31st 2019. Long-term opioid use was defined as at least two opioid dispensings within two subsequent 90-day periods, with a minimum average use of 10 MME/day for the first 90 days. Results The study population consisted of 693 495 post-operative opioid users (53.6% women), whereof 73.2% had not used opioids the year before surgery (new users). Among the postoperative opioid users, 3.8% were one-year long-term opioid users. The corresponding figures for new and previous opioid users were 0.4% and 13.1%, respectively. The highest proportions of long-term opioid use were found after transluminal endoscopy, eye surgery and assessments related to surgical procedures. In previous opioid users, the proportion of one-year long-term use was higher among women than men in all age groups, a difference that increased with age. Conclusions The proportion of postoperative long-term opioid use in Norway is generally low. We detected higher proportions of long-term opioid use after certain types of surgery, but our crude surgery definition warrants further examination. Previous opioid users pose a particular challenge in the management of postoperative pain. Trial registration The study used national health registry data from the period 2010–2019. A pre-registered analysis plan is available at Open Science Framework.

• Nes, Lise Solberg; Børøsund, Elin; Varsi, Cecilie; Eide, Hilde; Waxenberg, Lori B. & Weiss, Karen E. [Vis alle 14 forfattere av denne artikkelen] (2024). Living well with chronic pain: a 12-month randomized controlled trial revealing impact from the digital pain self-management program EPIO. Pain Reports. 9(4), s. 1–12. doi: 10.1097/PR9.0000000000001174. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Chronic pain affects a wide range of physical and psychological aspects of life for those impacted. Psychosocial treatment approaches may be of support, but outreach is still limited. Objectives: To evaluate the efficacy of EPIO, an evidence-informed, user-centered digital self-management intervention for people with chronic pain, in a 12-month randomized controlled trial. Methods: People living with chronic pain (N 5 266) were randomized to the EPIO intervention (n 5 132) or a usual-care control group (n 5 134). The intervention was delivered in a simple blended care model, and outcome measures collected at baseline, 6 months, and 12 months. Generalized linear models for repeated measures were fitted to compare groups over time. Results: Participants were primarily female (81%), median age 49 years (range 22–78), with heterogeneous pain conditions, and had lived with pain .5 years (77.6%). A mixed linear model with all timepoints included revealed no statistically significant group differences for the primary outcome of pain interference. Significant psychological benefits in favor of the intervention group were however detected for depression (P 5 0.022), self-regulatory fatigue (P 5 0.024), vitality (P 5 0.016), and mental health (P 5 0.047). Baseline to 12-month changes showed additional favorable effects for anxiety (between-group mean differences [MDs] 5 0.79, P 5 0.047), depression (MD 5 1.08, P 5 0.004), self-regulatory fatigue (MD 5 2.42, P 5 0.021), pain catastrophizing (MD 5 2.62, P 5 0.009), and health-related quality of life. Conclusions: The EPIO program aims to improve outreach of evidence-based pain self-management interventions. Findings demonstrate how using EPIO can lead to sustainable psychological change, enhancing mental health and health-related quality of life for people suffering from pain, providing a chance to live well with the pain

• Farnes, Nadine; Stubhaug, Audun; Hansson, Per & vambheim, Sara Magelssen (2024). H-Coil Repetitive Transcranial Magnetic Stimulation Relieves Pain and Symptoms of Anxiety and Depression in Patients With Chronic Peripheral Neuropathic Pain: A Randomized Sham-Controlled Crossover Study. Neuromodulation (Malden, Mass.). ISSN 1094-7159. 27(8), s. 1372–1382. doi: 10.1016/j.neurom.2024.09.002. Fulltekst i vitenarkiv Vis sammendrag

  Objectives This study aimed to investigate the analgesic effects of H-coil repetitive transcranial magnetic stimulation (rTMS) primarily targeting the hand area of the primary motor cortex (M1) in patients with peripheral neuropathic pain. Given that the H-coil has a wider reach than conventional coils, there is a possibility that targeting the hand motor cortex also may stimulate prefrontal areas. Thus, we also aimed to examine whether rTMS with an M1 target could produce effects on psychologic outcomes. Materials and Methods In total, 17 patients were randomly assigned to receive active or sham H-coil rTMS in a counterbalanced order. After a nine-week washout period, they crossed over to either active or sham rTMS, according to a double-blind crossover design. Each treatment period consisted of five daily rTMS sessions and a one- and three-week follow-up visit. The primary outcome was average usual pain intensity. Secondary outcomes included pain unpleasantness, dynamic and static mechanical allodynia, anxiety and depression, sleep, pain catastrophizing, function, and patients’ impression of change. Effects of rTMS were investigated using linear mixed model analyses. Results We found two significant interactions between treatment and time, indicating that active H-coil rTMS induced significant analgesic effects (t [134] = –2.18; p = .03; d = –0.10) and significant reductions in anxiety and depression compared with sham stimulation over the treatment course (t [73] = –2.14; p = .04; d = –0.09). The analgesic effect occurred two weeks after the treatment, and the effect on anxiety and depression occurred three weeks after treatment. No other significant interactions were found for the secondary variables. Conclusions Five days of H-coil rTMS targeting the hand area of M1 induced statistically significant effects on pain intensity. Moreover, rTMS improved symptoms of anxiety and depression, possibly because of the wide and deep reach of the H-coil.

• Stubhaug, Audun; Hansen, Johan Andre Liseth; Hallberg, Sara; Gustavsson, Anders; Eggen, Anne Elise & Nielsen, Christopher Sivert (2024). The costs of chronic pain - Long‐term estimates. European Journal of Pain. ISSN 1090-3801. 28(6), s. 960–977. doi: 10.1002/ejp.2234. Fulltekst i vitenarkiv Vis sammendrag

  Background: Chronic pain is a condition with severe impact on many aspects of life, including work, functional ability and quality of life, thereby reducing physical, mental and social well-being. Despite the high prevalence and burden of chronic pain, it has received disproportionally little attention in research and public policy and the societal costs of chronic pain remain largely unknown. This study aimed to describe the long-term healthcare and work absence costs of individuals with and without self-identified chronic pain.<p> <p>Methods: The study population were participants in two Norwegian population health studies (HUNT3 and Tromsø6). Participants were defined as having chronic pain based on a self-reported answer to a question on chronic pain in the health studies in 2008. Individuals in the study population were linked to four national register databases on healthcare resource use and work absence. <p>Results: In our study, 36% (n=63,782) self-reported to have chronic pain and the average years of age was 56.6. The accumulated difference in costs between those with and without chronic pain from 2010 to 2016 was €55,003 (CI: 54,414–55,592) per individual. Extrapolating this to the entire population suggests that chronic pain imposes a yearly burden of 4% of GDP. Eighty per cent of the costs were estimated to be productivity loss. <p>Conclusion: Insights from this study can provide a greater understanding of the extent of healthcare use and productivity loss by those with chronic pain and serve as an important basis for improvements in rehabilitation and quality of care, and the education of the public on the burden of chronic pain. <p>Significance: This was the first study to estimate the economic burden associated with chronic pain in the general population using linked individual-level administrative data and self-reported survey answers. We provide calculations showing that annual costs of chronic pain may be as high as €12 billion or 4% of GDP. Findings from this study highlight the need for a greater understanding of the substantial healthcare use and productivity losses among individuals with chronic pain.

• Janerås, Lars; Breivik, Harald Petter; LUNDELAND, BÅRD; Ringstad, Geir & Stubhaug, Audun (2024). Long-term intrathecal infusion of low-dose morphine effectively relieves symptoms of severe restless legs syndrome/Willis-Ekbom disease without inducing opioid tolerance. Pain. ISSN 0304-3959. 162(12), s. 2693–2697. doi: 10.1097/j.pain.0000000000003311. Fulltekst i vitenarkiv
• Melum, Tonje Anita; Steingrímsdóttir, Ólöf A.; Jacobsen, Henrik B.; Johnsen, Bente; Stubhaug, Audun & Schirmer, Henrik [Vis alle 8 forfattere av denne artikkelen] (2024). Associations between cognitive test scores and pain tolerance: The Tromsø study. Scandinavian Journal of Pain. ISSN 1877-8860. 24(1), s. 1–10. doi: 10.1515/sjpain-2023-0082. Fulltekst i vitenarkiv Vis sammendrag

  The aim of this study is to assess this relationship in a large population-based sample.<p> <p>Methods ‒ We included 5,753 participants (aged 40–84 years) from the seventh wave of the population-based Tromsø Study who had been examined with cognitive tests and experimental pain assessments, and for whom informa tion on covariates were available. Cox regression models were fitted using standardized scores on cognitive tests (12- word immediate recall test, digit symbol coding test, and Mini-Mental State Examination [MMS-E]) as the independent variable and cold pressor or cuff pressure pain tolerance as the dependent variables. Statistical adjustment was made for putative confounders, namely, age, sex, education, smoking, exercise, systolic blood pressure, body mass index, symptoms indicating anxiety or depression, analgesic use, and chronic pain. <p>Results ‒ In multivariate analysis, cold pressor tolerance time was significantly associated with test scores on the 12- word immediate recall test (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.90–0.97, p < 0.001), the digit symbol coding test (HR 0.94, 95% CI 0.89–0.98, p = 0.004), and the MMS-E (HR 0.93, 95% CI 0.90–0.96 p < 0.001). Tolerance to cuff pressure algometry was significantly associated with 12-word immediate recall (HR 0.94–0.97, p < 0.001) and Digit Symbol Coding test scores (HR 0.93, 95% CI 0.89–0.96, p < 0.001) while there was no significant association with Mini Mental State Examination test score (HR 0.98, 95% CI 0.95–1.00, p = 0.082). <p>Conclusion ‒ Lower pain tolerance was associated with poorer performance on cognitive tests.

• Hansen, Johan Andre Liseth; Heilig, Markus; Kalso, Eija; Stubhaug, Audun; Knutsson, Douglas & Sandin, Patrik [Vis alle 11 forfattere av denne artikkelen] (2023). Problematic opioid use among osteoarthritis patients with chronic post-operative pain after joint replacement: analyses from the BISCUITS study. Scandinavian Journal of Pain. ISSN 1877-8860. 23(2), s. 353–363. doi: 10.1515/sjpain-2022-0137. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Opioids are commonly used to manage pain, despite an increased risk of adverse events and complications when used against recommendations. This register study uses data of osteoarthritis (OA) patients with joint replacement surgery to identify and characterize problematic opioid use (POU) prescription patterns. Methods The study population included adult patients diagnosed with OA in specialty care undergoing joint replacement surgery in Denmark, Finland, Norway, and Sweden during 1 January 2011 to 31 December 2014. Those with cancer or OA within three years before the first eligible OA diagnosis were excluded. Patients were allocated into six POU cohorts based on dose escalation, frequency, and dosing of prescription opioids post-surgery (definitions were based on guidelines, previous literature, and clinical experience), and matched on age and sex to patients with opioid use, but not in any of the six cohorts. Data on demographics, non-OA pain diagnoses, cardiovascular diseases, psychiatric disorders, and clinical characteristics were used to study patient characteristics and predictors of POU. Results 13.7% of patients with OA and a hip/knee joint replacement were classified as problematic users and they had more comorbidities and higher pre-surgery doses of opioids than matches. Patients dispensing high doses of opioids pre-surgery dispensed increased doses post-surgery, a pattern not seen among patients prescribed lower doses pre-surgery. Being dispensed 1–4,500 oral morphine equivalents in the year pre-surgery or having a non-OA pain diagnosis was associated with post-surgery POU (OR: 1.44–1.50, and 1.11–1.20, respectively). Conclusions Based on the discovered POU predictors, the study suggests that prescribers should carefully assess pain management strategies for patients with a history of comorbidities and pre-operative, long-term opioid use. Healthcare units should adopt risk assessment tools and ensure that these patients are followed up closely. The data also demonstrate potential areas for further exploration in improving patient outcomes and trajectories.

• Bostrøm, Katrine; Børøsund, Elin; Eide, Hilde; Varsi, Cecilie; Kristjansdottir, Olöf Birna & Schreurs, Karlein M G [Vis alle 13 forfattere av denne artikkelen] (2023). Short-Term Findings From Testing EPIO, a Digital Self-Management Program for People Living With Chronic Pain: Randomized Controlled Trial. Journal of Medical Internet Research (JMIR). ISSN 1439-4456. 25. doi: 10.2196/47284. Fulltekst i vitenarkiv Vis sammendrag

  Background: Chronic pain conditions involve numerous physical and psychological challenges, and while psychosocial self-management interventions can be of benefit for people living with chronic pain, such in-person treatment is not always accessible. Digital self-management approaches could improve this disparity, potentially bolstering outreach and providing easy, relatively low-cost access to pain self-management interventions. Objective: This randomized controlled trial aimed to evaluate the short-term efficacy of EPIO (ie, inspired by the Greek goddess for the soothing of pain, Epione), a digital self-management intervention, for people living with chronic pain. Methods: Patients (N=266) were randomly assigned to either the EPIO intervention (n=132) or a care-as-usual control group (n=134). Outcome measures included pain interference (Brief Pain Inventory; primary outcome measure), anxiety and depression (Hospital Anxiety and Depression Scale), self-regulatory fatigue (Self-Regulatory Fatigue 18 scale), health-related quality of life (SF-36 Short Form Health Survey), pain catastrophizing (Pain Catastrophizing Scale), and pain acceptance (Chronic Pain Acceptance Questionnaire). Linear regression models used change scores as the dependent variables. Results: The participants were primarily female (210/259, 81.1%), with a median age of 49 (range 22-78) years and a variety of pain conditions. Analyses (n=229) after 3 months revealed no statistically significant changes for the primary outcome of pain interference (P=.84), but significant reductions in the secondary outcomes of depression (mean difference −0.90; P=.03) and self-regulatory fatigue (mean difference −2.76; P=.008) in favor of the intervention group. No other statistically significant changes were observed at 3 months (all P>.05). Participants described EPIO as useful (ie, totally agree or agree; 95/109, 87.2%) and easy to use (101/109, 92.7%), with easily understandable exercises (106/109, 97.2%). Conclusions: Evidence-informed, user-centered digital pain self-management interventions such as EPIO may have the potential to effectively support self-management and improve psychological functioning in the form of reduced symptoms of depression and improved capacity to regulate thoughts, feelings, and behavior for people living with chronic pain.

• Bouhassira, Didier; Jazat-Poindessous, Frédérique; Farnes, Nadine; Franchisseur, Claire; Stubhaug, Audun & Bismuth, Julie [Vis alle 9 forfattere av denne artikkelen] (2023). Comparison of the analgesic effects of "superficial" and "deep" repetitive transcranial magnetic stimulation in patients with central neuropathic pain: a randomized sham-controlled multicenter international crossover study. Pain. ISSN 0304-3959. 165(4), s. 884–892. doi: 10.1097/j.pain.0000000000003082. Fulltekst i vitenarkiv Vis sammendrag

  We directly compared the analgesic effects of "superficial" and 'deep" repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex in patients with central neuropathic pain. Fifty-nine consecutive patients were randomly assigned to active or sham "superficial" (using a figure-of-8 [F8]-coil) or "deep" (using a Hesed [H]-coil) stimulation according to a double-blind crossover design. Each treatment period consisted of 5 daily stimulation sessions and 2 follow-up visits at 1 and 3 weeks after the last stimulation session. The primary outcome was the comparison of the mean change in average pain intensity over the course of the treatment (group × time interaction). Secondary outcomes included neuropathic symptoms (NPSI), pain interference, patient global impression of change (PGIC), anxiety, depression, and catastrophizing. In total, 51 patients participated in at least one session of both treatments. There was a significant interaction between "treatment" and "time" (F = 2.7; P = 0.0024), indicating that both figure-8 (F8-coil) and H-coil active stimulation induced significantly higher analgesic effects than sham stimulation. The analgesic effects of both types of coils had a similar magnitude but were only moderately correlated (r = 0.39, P = 0.02). The effects of F8-coil stimulation appeared earlier, whereas the effects of H-coil stimulation were delayed, but tended to last longer (up to 3 weeks) as regards to several secondary outcomes (PGIC and total NPSI score). In conclusion, "deep" and "superficial" rTMS induced analgesic effects of similar magnitude in patients with central pain, which may involve different mechanisms of action.

• Årnes, Anders; Nielsen, Christopher Sivert; Stubhaug, Audun; Fjeld, Mats Kirkeby; Johansen, Aslak & Morseth, Bente [Vis alle 9 forfattere av denne artikkelen] (2023). Longitudinal relationships between habitual physical activity and pain tolerance in the general population. PLOS ONE. 18(5). doi: 10.1371/journal.pone.0285041. Fulltekst i vitenarkiv Vis sammendrag

  Article Authors Metrics Comments Media Coverage Peer Review Abstract Introduction Materials and methods Results Discussion Conclusion Supporting information Acknowledgments References Reader Comments Figures Abstract Physical activity (PA) might influence the risk or progression of chronic pain through pain tolerance. Hence, we aimed to assess whether habitual leisure-time PA level and PA change affects pain tolerance longitudinally in the population. Our sample (n = 10,732; 51% women) was gathered from the sixth (Tromsø6, 2007–08) and seventh (Tromsø7, 2015–16) waves of the prospective population-based Tromsø Study, Norway. Level of leisure-time PA (sedentary, light, moderate, or vigorous) was derived from questionnaires; experimental pain tolerance was measured by the cold-pressor test (CPT). We used ordinary, and multiple-adjusted mixed, Tobit regression to assess 1) the effect of longitudinal PA change on CPT tolerance at follow-up, and 2) whether a change in pain tolerance over time varied with level of LTPA. We found that participants with high consistent PA levels over the two surveys (Tromsø6 and Tromsø7) had significantly higher tolerance than those staying sedentary (20.4 s. (95% CI: 13.7, 27.1)). Repeated measurements show that light (6.7 s. (CI 3.4, 10.0)), moderate (CI 14.1 s. (9.9, 18.3)), and vigorous (16.3 s. (CI 6.0, 26.5)) PA groups had higher pain tolerance than sedentary, with non-significant interaction showed slightly falling effects of PA over time. In conclusion, being physically active at either of two time points measured 7–8 years apart was associated with higher pain tolerance compared to being sedentary at both time-points. Pain tolerance increased with higher total activity levels, and more for those who increased their activity level during follow-up. This indicates that not only total PA amount matters but also the direction of change. PA did not significantly moderate pain tolerance change over time, though estimates suggested a slightly falling effect possibly due to ageing. These results support increased PA levels as a possible non-pharmacological pathway towards reducing or preventing chronic pain.

• Melum, Tonje Anita; Årnes, Anders; Stigum, Hein; Stubhaug, Audun; Steingrímsdóttir, Ólöf Anna & Mathiesen, Ellisiv B. [Vis alle 7 forfattere av denne artikkelen] (2023). Pain tolerance after stroke: The Tromsø study. European Journal of Pain. ISSN 1090-3801. 27(7), s. 912–921. doi: 10.1002/ejp.2124. Fulltekst i vitenarkiv Vis sammendrag

  Background: Stroke lesions might alter pain processing and modulation by affecting the widely distributed network of brain regions involved. We aimed to compare pain tolerance in stroke survivors and stroke-free persons in the general population, with and without chronic pain.<p> <p>Methods: We included all participants of the sixth and seventh wave of the population-based Tromsø Study who had been tested with the cold pressor test (hand in cold water bath, 3°C, maximum time 106 s in the sixth wave and 120 s in the seventh) and who had information on previous stroke status and covariates. Data on stroke status were obtained from the Tromsø Study Cardiovascular Disease Register and the Norwegian Stroke Register. Cox regression models were fitted using stroke prior to study attendance as the independent variable, cold pressor endurance time as time variable and hand withdrawal from cold water as event. Statistical adjustments were made for age, sex, diabetes, hypertension, hyperlipidaemia, body mass index and smoking. <p>Results: In total 21,837 participants were included, 311 of them with previous stroke. Stroke was associated with decreased cold pain tolerance time, with 28% increased hazard of hand withdrawal (hazard ratio [HR] 1.28, 95% CI 1.10–1.50). The effect was similar in participants with (HR 1.28, 95% CI 0.99–1.66) and without chronic pain (HR 1.29, 95% CI 1.04–1.59). <p>Conclusions: Stroke survivors, with and without chronic pain, had lower cold pressor pain tolerance, with possible clinical implications for pain in this group. <p>Significance: We found lower pain tolerance in participants with previous stroke compared to stroke-free participants of a large, population-based study. The association was present both in those with and without chronic pain. The results may warrant increased awareness by health professionals towards pain experienced by stroke patients in response to injuries, diseases and procedures.

• Jacobsen, Henrik Børsting; Brun, Aurora; Stubhaug, Audun & Reme, Silje Endresen (2023). Stress specifically deteriorates working memory in peripheral neuropathic pain and fibromyalgia. Brain Communications. 5(4), s. S9–S15. doi: 10.1093/braincomms/fcad194. Fulltekst i vitenarkiv
• Hallberg, Sara; Rolfson, Ola; Karppinen, Jaro; Schiøttz-Christensen, Berit; Stubhaug, Audun & Grip, Emilie Toresson [Vis alle 9 forfattere av denne artikkelen] (2023). Economic burden of osteoarthritis - Multi-country estimates of direct and indirect costs from the BISCUITS study. Scandinavian Journal of Pain. ISSN 1877-8860. doi: 10.1515/sjpain-2023-0015. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Data from ‘BISCUITS’, a large Nordic cohort study linking several registries, were used to estimate differences in average direct and indirect costs between patients with osteoarthritis and controls (matched 1:1 based on birth year and sex) from the general population in Sweden, Norway, Finland and Denmark for 2017. Patients ≥18 years with ≥1 diagnosis of osteoarthritis (ICD-10: M15–M19) recorded in specialty or primary care (the latter available for a subset of patients in Sweden and for all patients in Finland) during 2011–2017 were included. Patients with a cancer diagnosis (ICD-10: C00–C43/C45–C97) were excluded. Productivity loss (sick leave and disability pension) and associated indirect costs were estimated among working-age adults (18–66 years). In 2017, average annual incremental direct costs among adults with osteoarthritis (n=1,157,236) in specialty care relative to controls ranged between €1,259 and €1,693 (p&lt;0.001) per patient across all countries. Total average annual incremental costs were €3,224–€4,969 (p&lt;0.001) per patient. Healthcare cost differences were mainly explained by osteoarthritis patients having more surgeries. However, among patients with both primary and secondary care data, primary care costs exceeded the costs of surgery. Primary care constituted 41 and 29 % of the difference in direct costs in Sweden and Finland, respectively. From a societal perspective, the total economic burden of osteoarthritis is substantial, and the incremental cost was estimated to €1.1–€1.3 billion yearly for patients in specialty care across the Nordic countries. When including patients in primary care, incremental costs rose to €3 billion in Sweden and €1.8 billion in Finland. Given the large economic impact, finding cost-effective and safe therapeutic strategies for these patients will be important.

• Melum, Tonje Anita; Vangberg, Torgil Riise; Johnsen, Liv-Hege; Steingrimsdottir, Olöf Anna; Stubhaug, Audun & Mathiesen, Ellisiv B. [Vis alle 7 forfattere av denne artikkelen] (2023). Gray matter volume and pain tolerance in a general population: the Tromsø study. Pain. ISSN 0304-3959. 164(8), s. 1750–1758. doi: 10.1097/j.pain.0000000000002871. Fulltekst i vitenarkiv
• Bostrøm, Katrine; Varsi, Cecilie; Eide, Hilde; Børøsund, Elin; Kristjansdottir, Olöf Birna & Schreurs, Karlein M. G. [Vis alle 12 forfattere av denne artikkelen] (2022). Engaging with EPIO, a digital pain self-management program: a qualitative study. BMC Health Services Research. 22(1), s. 1–15. doi: 10.1186/s12913-022-07963-x. Fulltekst i vitenarkiv Vis sammendrag

  Background: Chronic pain conditions entail significant personal and societal burdens and improved outreach of evidence-based pain self-management programs are needed. Digital cognitive-behavioral self-management inter- ventions have shown promise. However, evidence is still scarce and several challenges with such interventions for chronic pain exist. Exploring patients’ experiences and engagement with digital interventions may be an essential step towards developing meaningful digital self-management interventions for those living with chronic pain. Objectives: This study aimed to gain insight into the experiences of people with chronic pain when engaging with EPIO, an application (app)-based cognitive-behavioral pain self-management intervention program. Methods: Participants (N = 50) living with chronic pain received access to the EPIO intervention in a feasibility pilot- study for 3 months. During this time, all participants received a follow-up phone call at 2–3 weeks, and a subsample (n = 15) also participated in individual semi-structured interviews after 3 months. A qualitative design was used and thematic analysis was employed aiming to capture participants’ experiences when engaging with the EPIO interven- tion program. Results: Findings identifying program-related experiences and engagement were organized into three main topics, each with three sub-themes: (1) Engaging with EPIO; motivation to learn, fostering joy and enthusiasm, and helpful reminders and personalization, (2) Coping with pain in everyday life; awareness, practice and using EPIO in everyday life, and (3) The value of engaging with the EPIO program; EPIO – a friend, making peace with the presence of pain, and fostering communication and social support. Conclusions: This qualitative study explored participants’ experiences and engagement with EPIO, a digital self- management intervention program for people living with chronic pain. Findings identified valued aspects related to motivation for engagement, and showed how such a program may be incorporated into daily life, and encourage a sense of acceptance, social support and relatedness. The findings highlight vital components for facilitating digital program engagement and use in support of self-management for people living with chronic pain.

• Paccione, Charles Ethan; Stubhaug, Audun; Diep, Lien My; Rosseland, Leiv Arne & Jacobsen, Henrik Børsting (2022). Meditative-based diaphragmatic breathing vs. vagus nerve stimulation in the treatment of fibromyalgia—A randomized controlled trial: Body vs. machine. Frontiers in Neurology. 13. doi: 10.3389/fneur.2022.1030927. Fulltekst i vitenarkiv
• Hallberg, Sara; Rolfson, Ola; Karppinen, Jaro; Schiøttz-Christensen, Berit; Stubhaug, Audun & Fischer, Marcelo Rivano [Vis alle 12 forfattere av denne artikkelen] (2022). 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. Scandinavian Journal of Pain. ISSN 1877-8860. doi: 10.1515/sjpain-2021-0212. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Azulay, Naomi; Olsen, Roy Bjørkholt; Nielsen, Christopher Sivert; Stubhaug, Audun; Jenssen, Trond Geir & Schirmer, Henrik [Vis alle 9 forfattere av denne artikkelen] (2022). Reduced heart rate variability is related to the number of metabolic syndrome components and manifest diabetes in the sixth Tromsø study 2007–2008. Scientific Reports. 12(1). doi: 10.1038/s41598-022-15824-0. Fulltekst i vitenarkiv Vis sammendrag

  Both diabetes mellitus (DM) and the metabolic syndrome (MetS) are associated with autonomic neuropathy, which predisposes to cardiac events and death. Measures of heart rate variability (HRV) can be used to monitor the activity of the autonomic nervous system (ANS), and there are strong indications that HRV can be used to study the progression of ANS-related diabetes complications. This study aims to investigate diferences in HRV in healthy, MetS and diabetic populations. Based on 7880 participants from the sixth health survey in Tromsø (Tromsø 6, 2007–2008), we found a signifcant negative association between the number of MetS components and HRV as estimated from short-term pulse wave signals (PRV). This decrease in PRV did not appear to be linear, instead it leveled of after the third component, with no signifcant diference in PRV between the MetS and DM populations. There was a signifcant negative association between HbA1c and PRV, showing a decrease in PRV occurring already within the normal HbA1c range. The MetS and DM populations are diferent from healthy controls with respect to PRV, indicating impaired ANS in both conditions. In the future, a study with assessment of PRV measurements in relation to prospective cardiovascular events seems justifed.

• Lund, Charlotte Indre; Engdahl, Bo Lars; Rosseland, Leiv Arne; Stubhaug, Audun; Grimnes, Guri & Furberg, Anne-Sofie [Vis alle 8 forfattere av denne artikkelen] (2022). The association between age at menarche and chronic pain outcomes in women: the Tromsø Study, 2007 to 2016. Pain. ISSN 0304-3959. 163(9), s. 1790–1799. doi: 10.1097/j.pain.0000000000002579. Fulltekst i vitenarkiv Vis sammendrag

  Sex differences in chronic pain are well established with documented predominance in women. This study assessed relationships between age at menarche and chronic pain, site-specific chronic pain, pain characteristics, and chronic widespread pain (CWP). We used data from the Tromsø Study conducted in 2007 to 2008 and 2015 to 2016 (Tromsø 6 and Tromsø 7 waves) including participants aged 30 to 99 years. The associations between age at menarche and chronic pain were examined in Tromsø 6 (n 5 6449), Tromsø 7 (n 5 5681), and the combination of Tromsø 6 and Tromsø 7 (n 5 12,130). Tromsø 7 data were used further to examine the associations between age at menarche and site-specific chronic pain, 4 pain characteristics (pain duration, pain intensity, episode duration, and episode frequency), and CWP. All analyses were adjusted for body mass index, age, and economic status of the household in childhood. Lower age at menarche was associated with an increased risk of chronic pain in all 3 samples (risk ratio for each year delay in menarche 0.98, 95% CI [0.97 to 0.99] across samples). Risk differences were 20.014, CI 95% (20.02 to 20.005) in Tromsø 6, 20.011, CI 95% (20.02 to 20.02) in Tromsø 7, and 20.012, CI 95% (20.02 to 20.01) in the combined sample. Age at menarche was significantly associated with chronic pain in the neck, abdomen, and both arms, and CWP. Of the 4 pain characteristics, pain duration was statistically significant. We conclude that early menarche is an independent risk factor for pain across a broad spectrum of pain outcomes. Keywords: chronic pain, sex differences in pain, site-specific chronic pain, pain characteristics, chronic widespread pain, early menarche, exposure to estrogen

• Ho, Kevin Kwan Ngai; Skarpsno, Eivind S.; Nilsen, Kristian Bernhard; Ferreira, Paulo Herrique; Pinheiro, Marina & Hopstock, Laila Arnesdatter [Vis alle 11 forfattere av denne artikkelen] (2022). A bidirectional study of the association between insomnia, high-sensitivity C-reactive protein, and comorbid low back pain and lower limb pain. Scandinavian Journal of Pain. ISSN 1877-8860. 23(1), s. 110–125. doi: 10.1515/sjpain-2021-0197. Fulltekst i vitenarkiv Vis sammendrag

  Objectives - To examine the possible bidirectional association between insomnia and comorbid chronic low back pain (LBP) and lower limb pain and to explore whether high-sensitivity C-reactive protein (hsCRP) amplifies these associations. Methods - We calculated adjusted risk ratios (RR) with 95% confidence intervals (CI) for the development of insomnia and mild-to-severe chronic LBP and lower limb pain at 11 years follow-up in participants aged ≥32 years and with hsCRP ≤10 mg/L at baseline in 2007–2008: 3,714 without chronic LBP or lower limb pain (sample 1) and 7,892 without insomnia (sample 2). Results - Compared to participants without chronic pain, participants with comorbid chronic LBP and lower limb pain had a RR of insomnia of 1.37 (95% CI 1.12–1.66). Compared with participants without insomnia, participants with insomnia did not have an increased risk of comorbid chronic LBP and lower limb pain (RR: 1.06, 95% CI 0.76–1.46); however, participants with insomnia had a RR of chronic LBP of 1.20 (95% CI 1.02–1.42). There was no strong amplifying effect of elevated hsCRP (3.00–10.0 mg/L) on these associations. Conclusions - These findings suggest that elevated hsCRP does not amplify the associations between insomnia and mild-to-severe chronic LBP and lower limb pain. Further research using data on the temporal relation between insomnia, chronic pain, and inflammatory responses are required to fully understand the causal pathways.

• Fjeld, Mats Kirkeby; Årnes, Anders; Engdahl, Bo Lars; Morseth, Bente; Hopstock, Laila Arnesdatter & Horsch, Alexander [Vis alle 10 forfattere av denne artikkelen] (2022). Consistent pattern between physical activity measures and chronic pain levels: the Tromsø Study 2015 to 2016. Pain. ISSN 0304-3959. 164(4), s. 838–847. doi: 10.1097/j.pain.0000000000002773. Fulltekst i vitenarkiv Vis sammendrag

  Epidemiological literature on the relationship between physical activity and chronic pain is scarce and inconsistent. Hence, our aim was to assess the relationship applying comprehensive methodology, including self-reported and accelerometer measures of physical activity and different severity levels of chronic pain. We used data from the Tromsø Study (2015-2016). All residents in the municipality, aged 40 years and older were invited to participate (n=32,591, 51% women). A total of 21,083 (53% women) reported on questionnaires. Additionally, 6,778 participants (54% women) were invited to wear accelerometers (6,125 with complete measurements). Our exposure measures were self-reported leisure time physical activity, exercise frequency, duration and intensity and two accelerometer-measures (steps per day and minutes of moderate to vigorous physical activity per day). Outcome measurements were chronic pain and moderate-to-severe chronic pain. We used Poisson regression to estimate chronic pain prevalence and prevalence ratios for each physical activity measure, with adjustments for sex, age, education level, smoking history, and occupational physical activity. Our main analyses showed an inverse dose-response relationships between all physical activity measures and both severity measures of chronic pain, except that the dose-response relationship with exercise duration was only found for moderate-to-severe pain. All findings were stronger for the moderate-to-severe pain outcomes than for chronic pain. Robustness analyses gave similar results as the main analyses. We conclude that an inverse dose-response association between physical activity and chronic pain is consistent across measures. To summarize, higher levels of physical activity is associated with less chronic pain and moderate-to-severe chronic pain.

• Reme, Silje Endresen; Ljoså, Tone Marte; Stubhaug, Audun; Granan, Lars-Petter Ness; Falk, Ragnhild Sørum & Jacobsen, Henrik Børsting (2022). Perceived Injustice in Patients With Chronic Pain: Prevalence, Relevance, and Associations With Long-Term Recovery and Deterioration. Journal of Pain. ISSN 1526-5900. 23(7), s. 1196–1207. doi: 10.1016/j.jpain.2022.01.007. Fulltekst i vitenarkiv Vis sammendrag

  The Injustice Experience Questionnaire (IEQ) assesses the degree to which chronic pain sufferers perceive injustice in relation to their pain. The aim of the current study was to assess the prevalence and relevance of the IEQ and its association to perceived recovery and deterioration in a naturalistic pain clinic population. Data was obtained from the Oslo University Hospital's Pain Registry. Among 2,950 patients, the prevalence of low (<19), medium (19-29) and high (30+) IEQ was 39%, 32% and 29% respectively. High levels of injustice were positively associated with a wide range of adverse health outcomes. Differences between those with high vs low levels of IEQ were clinically significant for most health outcomes. A Venn diagram analysis showed considerable, but not complete, overlap between IEQ, pain catastrophizing, psychological distress and severe pain intensity. High IEQ was associated with reduced clinical recovery (OR 0.6, 95% CI 0.4-0.9) and deterioration (OR 3.6, 95% CI 2.1-6.2) at 12-months follow-up, however, not when controlling for pain-related disability and pain intensity. We conclude that perceived injustice is a prevalent and clinically relevant phenomenon in a chronic pain clinic population, and that more knowledge is needed regarding its role as indicator of poor prognosis and target for tailored treatment.

• Fladseth, Kristina; Lindekleiv, Haakon; Nielsen, Christopher Sivert; Øhrn, Andrea; Kristensen, Andreas & Mannsverk, Jan Torbjørn [Vis alle 15 forfattere av denne artikkelen] (2021). Low pain tolerance is associated with coronary angiography, coronary artery disease, and mortality: The Tromsø study. Journal of the American Heart Association (JAHA). 10(22). doi: 10.1161/JAHA.121.021291. Fulltekst i vitenarkiv Vis sammendrag

  BACKGROUND: The initial presentation to coronary angiography and extent of coronary artery disease (CAD) vary greatly among patients, from ischemia with no obstructive CAD to myocardial infarction with 3-vessel disease. Pain tolerance has been suggested as a potential mechanism for the variation in presentation of CAD. We aimed to investigate the association between pain tolerance, coronary angiography, CAD, and death.<p> <p>METHODS AND RESULTS: We identified 9576 participants in the Tromsø Study (2007–2008) who completed the cold-pressor pain test, and had no prior history of CAD. The median follow-up time was 10.4 years. We applied Cox-regression models with age as time-scale to calculate hazard ratios (HR). More women than men aborted the cold pressor test (39% versus 23%). Participants with low pain tolerance had 19% increased risk of coronary angiography (HR, 1.19 [95% CI, 1.03–1.38]) and 22% increased risk of obstructive CAD (HR, 1.22 [95% CI, 1.01–1.47]) adjusted by age as time-scale and sex. Among women who underwent coronary angiography, low pain tolerance was associated with 54% increased risk of obstructive CAD (HR, 1.54 [95% CI, 1.09–2.18]) compared with high pain tolerance. There was no association between pain tolerance and nonobstructive CAD or clinical presentation to coronary angiography (ie, stable angina, unstable angina, and myocardial infarction). Participants with low pain tolerance had increased risk of mortality after adjustment for CAD and cardiovascular risk factors (HR, 1.40 [95% CI, 1.19–1.64]).<p> <p>CONCLUSIONS: Low cold pressor pain tolerance is associated with a higher risk of coronary angiography and death.

• Paccione, Charles Ethan; Bruehl, Stephen; Diep, Lien My; Stubhaug, Audun; Rosseland, Leiv Arne & Jacobsen, Henrik Børsting (2021). The indirect impact of heart rate variability on cold pressor pain tolerance and intensity through psychological distress in individuals with chronic pain: The Tromsø Study. Pain Reports. 7(2). doi: 10.1097/PR9.0000000000000970. Fulltekst i vitenarkiv
• Jacobsen, Henrik Børsting; Stubhaug, Audun; Holmøy, Bjørn; Kvam, Tor-Morten & Reme, Silje Endresen (2021). Have Norwegians tried psilocybin, and do they accept it as a medicine? Journal of Psychedelic Studies. 5(1), s. 33–36. doi: 10.1556/2054.2021.00167. Fulltekst i vitenarkiv
• Varsi, Cecilie; Solem, Ingrid Konstanse Ledel; Eide, Hilde; Børøsund, Elin; Kristjansdottir, Olöf Birna & Heldal, Karina [Vis alle 12 forfattere av denne artikkelen] (2021). Health care providers' experiences of pain management and attitudes towards digitally supported self-management interventions for chronic pain: a qualitative study. BMC Health Services Research. 25(21). doi: 10.1186/s12913-021-06278-7. Fulltekst i vitenarkiv Vis sammendrag

  Chronic pain constitutes a significant burden for the individuals affected, and is a frequent reason why patients seek health care services. While in-person psychosocial interventions can be of support to people living with chronic pain, such interventions are not always accessible. eHealth interventions may provide greater accessibility, but the evidence and use of digital self-management solutions for chronic pain are still limited and the lack of health care provider input in the development process of such solutions a concern. Therefore, the aim of the current study was to investigate health care providers’ experiences of treating patients with chronic pain, their attitudes towards, and use of, digital solutions in pain management, and their suggestions for content and design elements for a potential digital pain self-management intervention. Methods: Twelve health care providers representing a variety of health care disciplines participated in semi-structured interviews. The interviews were analyzed using thematic analysis. Results: The material was analyzed into three main themes: [1] Patients with chronic pain and their current use of the health care services, [2] Health care providers’ own motivation and impression of patient prerequisites for use of digital self-management interventions, and [3] Suggestions for content and design elements in a digital self-management intervention for people living with chronic pain. The challenges faced by patients living with chronic pain were described as numerous. Despite interest and positive attitudes, few of the health care providers had used or recommended eHealth solutions to their patients. A range of potential content and functionality elements were identified, including aspects of motivation and engagement and providers also emphasized the importance of easy access and positive, personal content to support existing treatment. Conclusions: This study offers insights into health care providers’ considerations for the potential of digital self-management interventions supporting patients living with chronic pain. Findings indicate the need for change and a more comprehensive treatment approach to pain management. eHealth solutions may contribute to such change, and providers pointed to a need for health care provider involvement, timely support and follow-up as important factors for integrating digital pain self-management interventions into clinical care.

• Farbu, Erlend Hoftun; Rypdal, Martin; Skandfer, Morten; Steingrimsdottir, Olöf Anna; Brenn, Tormod & Stubhaug, Audun [Vis alle 8 forfattere av denne artikkelen] (2021). To tolerate weather and to tolerate pain: two sides of the same coin? The Tromsø Study 7. Pain. ISSN 0304-3959. 163(5), s. 878–886. doi: 10.1097/j.pain.0000000000002437. Fulltekst i vitenarkiv Vis sammendrag

  It is a common belief that weather affects pain. Therefore, we hypothesized that weather can affect pain tolerance. This study used data from over 18,000 subjects aged 40 years or older from the general population, who participated in the Tromsø Study 7. They underwent a one-time assessment of cuff algometry pressure pain tolerance (PPT) and cold pain tolerance (CPT), tested with a cold pressor test. The results showed a clear seasonal variation in CPT. The rate of withdrawal in the cold pressor test was up to 75% higher in months in the warmer parts of the year compared with January 2016. There was no seasonal variation in PPT. The study not only found a nonrandom short-term variation in PPT but also indications of such a variation in CPT. The intrinsic timescale of this short-term variation in PPT was 5.1 days (95% % confidence interval 4.0-7.2), which is similar to the observed timescales of meteorological variables. Pressure pain tolerance and CPT correlated with meteorological variables, and these correlations changed over time. Finally, temperature and barometric pressure predicted future values of PPT. These findings suggest that weather has a causal and dynamic effect on pain tolerance, which supports the common belief that weather affects pain.

• Petersen, Kristian Kjær; Vaegter, Henrik B.; Stubhaug, Audun; Wolff, André; Scammell, Brigitte E. & Arendt-Nielsen, Lars [Vis alle 7 forfattere av denne artikkelen] (2021). The predictive value of quantitative sensory testing: a systematic review on chronic postoperative pain and the analgesic effect of pharmacological therapies in patients with chronic pain. Pain. ISSN 0304-3959. 162(1), s. 31–44. doi: 10.1097/j.pain.0000000000002019. Fulltekst i vitenarkiv
• Bramness, Jørgen G.; Hjellvik, Vidar; Stubhaug, Audun & Skurtveit, Svetlana (2021). Possible opioid-saving effect of cannabis-based medicine using individual-based data from the Norwegian Prescription Database. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. s. 1–9. doi: 10.1111/bcpt.13660. Fulltekst i vitenarkiv Vis sammendrag

  Some ecological studies have shown that areas with higher use of cannabis may have lower opioid use and fewer opioid-related problems. Newer studies are questioning this finding. Few individually based studies have been performed. Using data from the Norwegian Prescription Database, this study investigated the individual level effect of prescribed cannabis extract (Sativex®) in prescription opioid users on their opioid use in the following year. Looking at all those filling a prescription for Sativex®, opioid use was only marginally lowered in the follow-up period. Some Sativex® users, however, filled more prescriptions for Sativex® and were able to reduce their opioid use substantially. Further studies are needed to elucidate more details on these patients, so as to know who can benefit from such cannabis-based extracts in reducing their opioid use.

• Jacobsen, Henrik Børsting; Stiles, Tore C; Stubhaug, Audun; Landrø, Nils Inge & Hansson, Per (2021). Comparing objective cognitive impairments in patients with peripheral neuropathic pain or fibromyalgia. Scientific Reports. 11. doi: 10.1038/s41598-020-80740-0. Fulltekst i vitenarkiv Vis sammendrag

  Existing studies on cognitive impairments in chronic pain do not investigate peripheral neuropathic pain (PNP) or compare pain conditions in a satisfactory manner. Here we aimed to compare executive dysfunctions in PNP patients with fibromyalgia (FM) and healthy controls (HC). Patients who self-reported cognitive impairments were assessed according to criteria for PNP or FM. Seventy-three patients met criteria and completed testing on executive functioning and IQ measures. We also included twenty matched healthy controls. Regression models controlling for age, sex and IQ, tested associations between group category (PNP, FM or HC) and outcomes. If a substantial association was detected, we followed up with head-to-head comparisons between PNP and FM. Multivariate regression models then tested associations between executive functioning and pain type, controlling for significant confounders. Results from head-to-head comparison between pain conditions showed significant differences on years lived with pain (FM > PNP), the use of anticonvulsants (PNP > FM) and use of analgesics (PNP > FM). When controlled for all significant differences, PNP patients had significantly lower scores on an attention-demanding cued-recall task compared to FM. Poor performance on attention-demanding cued-recall task was associated with PNP, which translate into problems with retaining fast-pace or advanced information.

• Tanha, Hamzeh M; Martin, Nicholas G; Whitfield, John B; Nyholt, Dale R; Gormley, Padhraig & Anttila, Verneri [Vis alle 111 forfattere av denne artikkelen] (2021). Association and genetic overlap between clinical chemistry tests and migraine. Cephalalgia. ISSN 0333-1024. 41(11-12), s. 1208–1221. doi: 10.1177/03331024211018131. Fulltekst i vitenarkiv
• Paccione, Charles Ethan; Diep, Lien My; Stubhaug, Audun & Jacobsen, Henrik Børsting (2020). Motivational nondirective resonance breathing versus transcutaneous vagus nerve stimulation in the treatment of fibromyalgia: study protocol for a randomized controlled trial. Trials. 21:808, s. 1–23. doi: 10.1186/s13063-020-04703-6. Fulltekst i vitenarkiv Vis sammendrag

  Background Chronic widespread pain (CWP), including fibromyalgia (FM), affects one in every ten adults and is one of the leading causes of sick leave and emotional distress. Due to an unclear etiology and a complex pathophysiology, FM is a condition with few, if any, effective and safe treatments. However, current research within the field of vagal nerve innervation suggests psychophysiological and electrical means by which FM may be treated. This study will investigate the efficacy of two different noninvasive vagal nerve stimulation techniques for the treatment of FM. Methods The study will use a randomized, single-blind, sham-controlled design to investigate the treatment efficacy of motivational nondirective resonance breathing (MNRB™) and transcutaneous vagus nerve stimulation (Nemos® tVNS) on patients diagnosed with FM. Consenting FM patients (N = 112) who are referred to the Department of Pain Management and Research at Oslo University Hospital, in Oslo, Norway, will be randomized into one of four independent groups. Half of these participants (N = 56) will be randomized to either an experimental tVNS group or a sham tVNS group. The other half (N = 56) will be randomized to either an experimental MNRB group or a sham MNRB group. Both active and sham treatment interventions will be delivered twice per day at home, 15 min/morning and 15 min/evening, for a total duration of 2 weeks (14 days). Participants are invited to the clinic twice, once for pre- and once for post-intervention data collection. The primary outcome is changes in photoplethysmography-measured heart rate variability. Secondary outcomes include self-reported pain intensity on a numeric rating scale, changes in pain detection threshold, pain tolerance threshold, and pressure pain limit determined by computerized pressure cuff algometry, blood pressure, and health-related quality of life. Discussion The described randomized controlled trial aims to compare the efficacy of two vagal nerve innervation interventions, MNRB and tVNS, on heart rate variability and pain intensity in patients suffering from FM. This project tests a new and potentially effective means of treating a major public and global health concern where prevalence is high, disability is severe, and treatment options are limited. Trial registration ClinicalTrials.gov NCT03180554. Registered on August 06, 2017.

• Årnes, Anders; Nielsen, Christopher Sivert; Stubhaug, Audun; Fjeld, Mats Kirkeby; Hopstock, Laila Arnesdatter & Horsch, Alexander [Vis alle 10 forfattere av denne artikkelen] (2020). Physical activity and cold pain tolerance in the general population. European Journal of Pain. ISSN 1090-3801. doi: 10.1002/ejp.1699. Fulltekst i vitenarkiv Vis sammendrag

  <p>Background - The relationship between habitual physical activity (PA) and experimental pain tolerance has been investigated in small samples of young, healthy and/or single‐sex volunteers. We used a large, population‐based sample to assess this relationship in men and women with and without chronic pain. <p>Methods - We used data from the sixth and seventh Tromsø Study surveys (2007–2008; 2015–2016), with assessed pain tolerance of participants with the cold pressor test (CPT: dominant hand in circulating cold water at 3°C, maximum test time 106 s), and self‐reported total amount of habitual PA in leisure time (n = 19,087), exercise frequency (n = 19,388), exercise intensity (n = 18,393) and exercise duration (n = 18,343). A sub‐sample had PA measured by accelerometers (n = 4,922). We used Cox regression to compare CPT tolerance times between self‐reported PA levels. For accelerometer‐measured PA, we estimated hazard ratios for average daily activity counts, and for average daily minutes of moderate‐to‐vigorous PA done in bouts lasting 10 min or more. Models were tested for PA‐sex, and PA‐chronic pain and PA‐moderate‐to‐severe chronic pain interactions. <p>Results - Leisure‐time PA, exercise intensity and exercise duration were positively associated with CPT tolerance (p < .001; p = .011; p < .001). More PA was associated with higher CPT tolerance. At high levels of leisure‐time PA and exercise intensity, men had a significantly higher CPT tolerance than women. Accelerometer‐measured PA was not associated with CPT tolerance. <p>Conclusions - This study is one of the first to show that higher self‐reported habitual PA was connected to higher experimental pain tolerance in a population‐based sample, especially for men. This was not found for accelerometer‐measured PA. <p>Significance - This study finds that higher level of self‐reported leisure‐time physical activity is associated with increased cold pressor pain tolerance in a large population‐based sample. Though present in both sexes, the association is strongest among men. Despite the robust dose–response relationship between pain tolerance and self‐reported activity level, no such relationship was found for accelerometer‐measured activity, reflecting a possible discrepancy in the aspect of physical activity measured. Though the study design does not permit causal conclusions, the findings suggest that increasing physical activity may increase pain tolerance in the general population.

• Bostrøm, Katrine; Børøsund, Elin; Varsi, Cecilie; Eide, Hilde; Nordang, Elise Flakk & Schreurs, Karlein [Vis alle 12 forfattere av denne artikkelen] (2020). Digital self-management in support of patients living with chronic pain: Feasibility pilot study. JMIR Formative Research. 4:e23893(10), s. 1–15. doi: 10.2196/23893. Fulltekst i vitenarkiv Vis sammendrag

  Background: Chronic pain can be complex and taxing to live with, and treatment and support require a multicomponent approach, which may not always be offered or available. Smartphones, tablets, and personal computers are already incorporated into patients’ daily lives, and therefore, they can be used to communicate, educate, and support self-management. Although some web-based self-management interventions exist, research examining the evidence and effect of digital solutions supporting self-management for patients living with chronic pain is limited, findings are inconclusive, and new innovative ideas and solutions are needed. Objective: This feasibility pilot study aimed to explore the system use, perceived usefulness, ease of use, and preliminary effects of EPIO, an app-based cognitive-behavioral pain self-management intervention program for patients living with chronic pain. Methods: The EPIO intervention was delivered in a blended-care model containing (1) one face-to-face introduction session, (2) nine cognitive behavior–based pain self-management modules, delivered in an app-based format for smartphones or tablets, and (3) one follow-up phone call at 2 to 3 weeks after the introduction session. Patients living with chronic pain (N=50) completed pre-post outcome measures at baseline and 3 months after the introduction session, with registration of system use (ie, log data) until 6 months. The use, perceived usefulness, and ease of use of the EPIO program were examined through system use data, as well as a study-specific use/usability questionnaire and the System Usability Scale (SUS). Outcome measures to test feasibility of use and estimate preliminary effects included the Brief Pain Inventory, health-related quality of life (HRQoL) scale, Hospital Anxiety and Depression Scale, Self-Regulatory Fatigue scale, Pain Catastrophizing Scale, and Chronic Pain Acceptance Questionnaire. Results: Participants (N=50) had a median age of 52 years (range 29-74 years) at inclusion and were mainly female (40/50, 80%). Thirty-one participants completed at least six of the nine modules within the 3-month study period (62% completion rate). Forty-five participants completed outcome measures at 3 months, and the EPIO program was rated as useful (ie, “totally agree”or “agree”; 39/45, 87%) and easy to use (42/45, 93%), and as having easily understandable exercises (44/45, 98%). The average overall system usability (SUS) score was 85.7, indicating grade A and excellent system usability. Preliminary psychosocial outcome measure estimates showed primarily nonsignificant pre-post intervention improvements at 3 months, but with significant positive effects related to some aspects of HRQoL (bodily pain, P=.02 and change, P=.049). Conclusions: Digital self-management intervention programs may be of use and support for patients living with chronic pain. In this feasibility study, EPIO showed an acceptable program completion rate and was rated as useful and easy to use, with excellent user satisfaction. Program optimization and efficacy testing in a large-scale randomized controlled trial are warranted and in progress.

• Guo, Yanjun; Rist, Pamela M.; Daghlas, Iyas; Giulianini, Franco; Winsvold, Bendik K S & Zwart, John-Anker [Vis alle 50 forfattere av denne artikkelen] (2020). A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine. Nature Communications. 11. doi: 10.1038/s41467-020-17002-0. Fulltekst i vitenarkiv Vis sammendrag

  Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg; P = 5.57 × 10−25) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg; P = 2.60 × 10−07) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg; P = 3.65 × 10−07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.

• Sargurupremraj, Muralidharan; Suzuki, Hideaki; Jian, Xueqiu; Sarnowski, Chloé; Evans, Tavia E. & Bis, Joshua C. [Vis alle 50 forfattere av denne artikkelen] (2020). Cerebral small vessel disease genomics and its implications across the lifespan. Nature Communications. 11. doi: 10.1038/s41467-020-19111-2. Fulltekst i vitenarkiv Vis sammendrag

  Abstract White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

• Steingrímsdóttir, Ólöf Anna; Engdahl, Bo Lars; Hansson, Per; Stubhaug, Audun & Nielsen, Christopher Sivert (2020). The Graphical Index of Pain: a new web-based method for high-throughput screening of pain. Pain. ISSN 0304-3959. 161(10), s. 2255–2262. doi: 10.1097/j.pain.0000000000001899. Fulltekst i vitenarkiv Vis sammendrag

  This article is the first to present the Graphical Index of Pain (GRIP), a new user-friendly web-based method for high-throughput screening of pain. The long-term goal of the method is to improve global standardization of pain measurements. GRIP consists of a hierarchical body map with 10 first-tier body regions, and a second tier with multiple pain loci (167 among men, 168 among women), which provides detailed information about pain location and distribution. Follow-up questions for first-tier regions include the following pain characteristics: onset, episode frequency, episode duration (including constant pain), intensity, bothering, depth of pain, and effects on sleep and daily activities. The first implementation of GRIP was in the Tromsø Study (2015-2016), a population-based study of adults aged 40 to 99 years. In total, 21,083 individuals participated in the study, and 96% (n = 20,263; age 40-96 years) completed GRIP. Pain intensity at first-tier regions and pain location and distribution at second-tier regions are in this article presented by sex-stratified customized heat maps showing large sex difference. Mean time to mark the first- and second-tier regions was 74 seconds. In conclusion, GRIP allows for high-resolution assessment and presentation of pain location and distribution with minimal use of time.

• Solem, Ingrid Konstanse Ledel; Varsi, Cecilie; Eide, Hilde; Kristjansdottir, Olöf Birna; Børøsund, Elin & Schreurs, Karlein M.G. [Vis alle 14 forfattere av denne artikkelen] (2020). A User-Centered Approach to an Evidence-Based Electronic Health Pain Management Intervention for People With Chronic Pain: Design and Development of EPIO. Journal of Medical Internet Research (JMIR). ISSN 1439-4456. 22(1). doi: 10.2196/15889. Fulltekst i vitenarkiv Vis sammendrag

  Background: Chronic pain conditions are complicated and challenging to live with. Electronic health (eHealth) interventions show promise in helping people cope with chronic illness, including pain. The success of these interventions depends not only on the technology and intervention content but also on the users’ acceptance and adherence. Involving all stakeholders (eg, patients, spouses, health care providers, designers, software developers, and researchers) and exploring their input and preferences in the design and development process is an important step toward developing meaningful interventions and possibly strengthening treatment outcomes. Objective: The aim of this study was to design and develop a user-centered, evidence-based eHealth self-management intervention for people with chronic pain. Methods: The study employed a multidisciplinary and user-centered design approach. Overall, 20 stakeholders from the project team (ie, 7 researchers, 5 editors, 7 software developers, and 1 user representative), together with 33 external stakeholders (ie, 12 health care providers, 1 health care manger, 1 eHealth research psychologist, and 17 patients with chronic pain and 2 of their spouses) participated in a user-centered development process that included workshops, intervention content development, and usability testing. Intervention content was developed and finalized based on existing evidence, stakeholder input, and user testing. Stakeholder input was examined through qualitative analyses with rapid and in-depth analysis approaches. Results: Analyses from stakeholder input identified themes including a need for reliable,trustworthy, and evidence-based content, personalization, options for feedback, behavioral tracking, and self-assessment/registration as factors to include in the intervention. Evidence-based intervention content development resulted in one face-to-face introduction session and 9 app-based educational and exercise-based modules. Usability testing provided further insight into how to optimize the design of the intervention to the user group, identifying accessibility and a simple design to be essential. Conclusions: The design and development process of eHealth interventions should strive to combine well-known evidence-based concepts with stakeholder input. This study, designing and developing the pain management intervention EPIO, illustrates how a stakeholder-centered design approach can provide essential input in the development of an eHealth self-management intervention for people with chronic pain.

• Farbu, Erlend Hoftun; Skandfer, Morten; Nielsen, Christopher Sivert; Brenn, Tormod; Stubhaug, Audun & Höper, Anje Christina (2019). Working in a cold environment, feeling cold at work and chronic pain: a cross-sectional analysis of the Tromsø Study. BMJ Open. 9:e031248(11), s. 1–8. doi: 10.1136/bmjopen-2019-031248. Fulltekst i vitenarkiv Vis sammendrag

  <i>Aim</i> - The aim of this study was to investigate if working in a cold environment and feeling cold at work are associated with chronic pain (ie, lasting ≥3 months).<p> <p><i>Methods</i> - We used data from the sixth survey (2007–2008) of the Tromsø Study. Analyses included 6533 men and women aged 30–67 years who were not retired, not receiving full-time disability benefits and had no missing values. Associations between working in a cold environment, feeling cold at work and self-reported chronic pain were examined with logistic regression adjusted for age, sex, education, body mass index, insomnia, physical activity at work, leisure time physical activity and smoking.<p> <p><i>Results</i> - 779 participants reported working in a cold environment ≥25% of the time. This exposure was positively associated with pain at ≥3 sites (OR 1.57; 95% CI 1.23 to 2.01) and with neck, shoulder and leg pain, but not with pain at 1–2 sites. Feeling cold sometimes or often at work was associated with pain at ≥3 sites (OR 1.58; 95% CI 1.22 to 2.07 and OR 3.90; 95% CI 2.04 to 7.45, respectively). Feeling cold often at work was significantly and positively associated with pain at all sites except the hand, foot, stomach and head.<p> <p><i>Conclusion</i> - Working in a cold environment was significantly associated with chronic pain. The observed association was strongest for pain at musculoskeletal sites and for those who often felt cold at work.

Se alle arbeider i NVA

• Solbakken, Siri Marie; Riemann, Sebastian; Page, Christian Magnus; Holvik, Kristin; Kuiper, Lieke M & Czajkowski, Nikolai Olavi [Vis alle 12 forfattere av denne artikkelen] (2026). Reduced pain tolerance in asthma and COPD: the Tromsø and Rotterdam studies. Scandinavian Journal of Pain. ISSN 1877-8860. 26(1), s. eA4–eA5. doi: https:/www.degruyterbrill.com/document/doi/10.1515/sjpain-2026-0013/html. Fulltekst i vitenarkiv
• Børøsund, Elin; Hagen, Milada; Varsi, Cecilie; Eide, Hilde; Waxenberg, Lori B. & Weiss, Karen E. [Vis alle 14 forfattere av denne artikkelen] (2026). Exploring models for delivery of the digital pain self‑management program EPIO. doi: 10.1093/abm/kaag012. Fulltekst i vitenarkiv
• Børøsund, Elin; Hagen, Milada; Varsi, Cecilie; Eide, Hilde; Waxenberg, Lori B. & Weiss, Karen Elizabeth [Vis alle 12 forfattere av denne artikkelen] (2025). Digital Pain management: Can Stand-alone Delivery have Impact? Fulltekst i vitenarkiv
• Nes, Lise Solberg; Børøsund, Elin; Varsi, Cecilie; Eide, Hilde; Kristjansdottir, Olöf Birna & Waxenberg, Lori B. [Vis alle 16 forfattere av denne artikkelen] (2025). Digital Pain Self-Management with EPIO: Design, Development, Evaluation - and Future Directions. Fulltekst i vitenarkiv
• Fjeld, Mats Kirkeby; Årnes, Anders; Engdahl, Bo Lars; Morseth, Bente; Hopstock, Laila Arnesdatter & Horsch, Alexander [Vis alle 12 forfattere av denne artikkelen] (2025). Reply to Verbrugghe et al. Pain. ISSN 0304-3959. 166(10), s. e488–e490. doi: 10.1097/j.pain.0000000000003693. Fulltekst i vitenarkiv
• Lund, Charlotte; Rosseland, Leiv Arne; Steingrímsdóttir, Ólöf Anna; Engdahl, Bo Lars; Stubhaug, Audun & Furberg, Anne-Sofie [Vis alle 7 forfattere av denne artikkelen] (2025). Reply to Huang and Chen. Pain. ISSN 0304-3959. 166(3), s. 710–711. doi: 10.1097/j.pain.0000000000003467. Fulltekst i vitenarkiv
• Nes, Lise Solberg; Børøsund, Elin; Varsi, Cecilie; Eide, Hilde; Waxenberg, Lori B. & Weiss, Karen Elizabeth [Vis alle 14 forfattere av denne artikkelen] (2024). Results from a One-Year Randomized Controlled Trial with the Digital Pain Self-management Intervention EPIO. Fulltekst i vitenarkiv
• Strand, Elin Bolle; Nes, Lise Solberg; Børøsund, Elin; Eide, Hilde; Kristjansdottir, Olöf Birna & Schreurs, Karlein MG [Vis alle 14 forfattere av denne artikkelen] (2024). Participants’ experiences after using the EPIO pain self-management program – a qualitative study EAPM European association of psychosomatic medicine. Fulltekst i vitenarkiv
• Strand, Elin Bolle; Nes, Lise Solberg; Børøsund, Elin; Bostrøm, Katrine; Eide, Hilde & Varsi, Cecilie [Vis alle 15 forfattere av denne artikkelen] (2024). Det app-baserte smertemestringsprogrammet EPIO – resultater og status. Fulltekst i vitenarkiv
• Ekholdt, Christopher; Granan, Lars-Petter Ness; Stubhaug, Audun; Toennis, Maren; Salthe, Stine & LUNDELAND, BÅRD (2024). Ryggmargsstimulering har en plass i behandling av langvarige smertetilstander. 144(7). doi: 10.4045/tidsskr.24.0120. Fulltekst i vitenarkiv
• Strand, Elin Bolle; Nes, Lise Solberg; Børøsund, Elin; Eide, Hilde; Kristjansdottir, Olöf Birna & Schreurs, Karlein M. G. [Vis alle 14 forfattere av denne artikkelen] (2024). Participants’ experiences after using the EPIO pain self-management program – a qualitative study. Fulltekst i vitenarkiv
• Nes, Lise Solberg; Børøsund, Elin; Varsi, Cecilie; Kristjansdottir, Olöf Birna; Schreurs, Karlein MG & Waxenberg, Lori B. [Vis alle 12 forfattere av denne artikkelen] (2024). EPIO©™ Et digitalt støtteprogram for de som lever med langvarige smerter. Fulltekst i vitenarkiv
• Strand, Elin Bolle; Nes, Lise Solberg; Børøsund, Elin; Varsi, Cecilie; Kristjansdottir, Olöf Birna & Schreurs, Karlein M.G. [Vis alle 14 forfattere av denne artikkelen] (2024). EPIO - et digitalt støtteprogram for de som lever med langvarige smerter: Metoder og resultater. Fulltekst i vitenarkiv
• Nes, Lise Solberg; Børøsund, Elin; Varsi, Cecilie; Eide, Hilde; Waxenberg, Lori & Weiss, Karen E. [Vis alle 13 forfattere av denne artikkelen] (2024). Results from a one-year randomized controlled trial with the digital pain self-management intervention EPIO. Annals of Behavioral Medicine. ISSN 0883-6612. doi: 10.1093/abm/kaae014. Fulltekst i vitenarkiv
• vambheim, Sara Magelssen; Hjellvik, Vidar; Odsbu, Ingvild; Skurtveit, Svetlana Ondrasova; Ekholdt, Christopher & Granan, Lars-Petter Ness [Vis alle 8 forfattere av denne artikkelen] (2023). Postoperative Opioid Use in Norway - Patterns of Prolonged Use. Fulltekst i vitenarkiv
• Borchgrevink, Petter Chr.; Westgaard, Tone Elise; Schjødt, Borrik & Stubhaug, Audun (2023). Behov for felles innsats mot opioidproblemene. Fulltekst i vitenarkiv
• Nes, Lise Solberg; Børøsund, Elin; Varsi, Cecilie; Eide, Hilde; Kristjansdottir, Olöf Birna & Schreurs, Karlein MG [Vis alle 14 forfattere av denne artikkelen] (2023). EPIO – a digital pain self-management program for people living with chronic pain. Fulltekst i vitenarkiv
• Bostrøm, Katrine; Varsi, Cecilie; Eide, Hilde; Børøsund, Elin; Kristjansdottir, Olöf Birna & Schreurs, Karlein MG [Vis alle 12 forfattere av denne artikkelen] (2022). Pasienters erfaringer med det digitale smertemestringsprogrammet EPIO: en kvalitativ studie. Fulltekst i vitenarkiv
• Støle, Hanne Stavenes; Varsi, Cecilie; Eide, Hilde; Kristjansdottir, Olöf Birna; Børøsund, Elin & Waxenberg, Lori B. [Vis alle 13 forfattere av denne artikkelen] (2022). Presentasjon av EPIO - Å leve med langvarie smerter. Fulltekst i vitenarkiv
• Torp-Joakimsen, Kjell Aage Moe; Dimmen, Sigbjørn & Stubhaug, Audun (2022). Local infiltration analgesia versus interscalene nerve block for postoperative pain control after primary shoulder arthroplasty: A retrospective study including 100 patients. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background: The aim of this study was to compare the efficacy of single bolus local infiltration analgesia (LIA) versus continous interscalene nerve block (ISB) for early postoperative pain control after total shoulder arthroplasty (TSA). The null hypothesis was no difference between treatments. Methods: A retrospective study including patients from 2021.05.01 and backwards in time until both groups had included 50 patients. All patients who underwent primary TSA for shoulder osteoarthritis were eligible for inclusion. Patients in the ISB group received a perineural catheter at the ipsilateral interscalene plexus prior to operation, and after a preoperative bolus of local anaesthetic had a postoperative continous infusion of ropivacaine 2 mg/ml for up to 2 days. For the LIA group, the surgeon injected a weight dependent dose of 2 mg/ml ropivacaine with epinephrine intraoperatively. The primary outcome was mean opoid consumption @ 1,4,24 and 48-hour postoperatively. The secondary outcomes were opioid consumption perioperatively, complications and need for adjuvant pain treatment as lidocaine or ketamine infusions or clonidine boluses. The sample size was calculated with an α=0,05 and β=0,2. Results: The study included 100 patients (50 LIA and 50 ISB patients) with comparable patient group regarding age, weight, height, sex, ASA-status and preoperative CN symptome score. For all time points the first 24 hours, the ISB group had a significantly lower opioid consumption. The final 24 hour opoid consumptions were similar, but the total 48 hour opoid consumption was significantly lower in the ISB-group. Secondarily the perioperative opoid consumption was statistcally lower in the ISB group, and the LIA group had significantly more need for adjuvants. Most excluded patients in the LIA group had to resort to a rescue ISB postoperatively. Conclusion: Continous ISB is superior for early postoperative pain control after TSA compared to a single bolus LIA group using MEQ as endpoint. Keywords: Total shoulder arthroplasty; early postoperative pain; interscalene nerve block; local infiltration analgesia; opioid consumption.

• Bekkenes, Maria Egeland; Stubhaug, Audun; Reme, Silje Endresen; Fagerland, Morten Wang; Michelsen, Trond Melbye & Rosseland, Leiv Arne (2022). Effects of 2.5 IU oxytocin or 100 μg carbetocin on pain intensity and opioid consumption after planned cesarean delivery; a randomized controlled trial. Fulltekst i vitenarkiv
• Bostrøm, Katrine; Varsi, Cecilie; Eide, Hilde; Børøsund, Elin; Nordang, Elise Flakk & Stubhaug, Audun [Vis alle 7 forfattere av denne artikkelen] (2022). EPIO™ – engasjerende og støttende digital smertemestring for pasienter med langvarig smerte. Best Practice. ISSN 1329-1874. Fulltekst i vitenarkiv
• Bostrøm, Katrine; Varsi, Cecilie; Børøsund, Elin; Kristjansdottir, Olöf Birna; Schreurs, Karlein MG & Waxenberg, Lori B. [Vis alle 11 forfattere av denne artikkelen] (2022). Pasienters erfaringer med det digitale smertemestringsprogrammet EPIO: en kvalitativ studie. Fulltekst i vitenarkiv
• Bostrøm, Katrine; Børøsund, Elin; Varsi, Cecilie; Eide, Hilde; Nordang, Elise Flakk & Schreurs, Karlein MG [Vis alle 12 forfattere av denne artikkelen] (2022). Bruk og opplevd nytte av det digitale smertemestringsprogrammet EPIO: en pilotstudie. Fulltekst i vitenarkiv
• Bostrøm, Katrine; Børøsund, Elin; Varsi, Cecilie; Eide, Hilde; Nordang, Elise Flakk & Schreurs, Karlein MG [Vis alle 12 forfattere av denne artikkelen] (2022). Bruk og opplevd nytte av det digitale smertemestringsprogrammet EPIO: en pilot studie. Fulltekst i vitenarkiv
• Bostrøm, Katrine; Børøsund, Elin; Eide, Hilde; Varsi, Cecilie; Kristjansdottir, Olöf Birna & Schreurs, Karlein MG [Vis alle 13 forfattere av denne artikkelen] (2022). Short-term Efficacy Findings from a Randomized Controlled Trial with EPIO – a Digital Pain Self-Management Program. Fulltekst i vitenarkiv
• Seines, Ellisiv; Fretland, Bjørn; Gál, Peter; Berg, Kristin Sandal; Stubhaug, Audun & Løberg-Emanuelsen, L [Vis alle 8 forfattere av denne artikkelen] (2022). Low systemic concentrations of bupivacaine from topical anesthesia of the tonsillar beds after tonsillectomy. Fulltekst i vitenarkiv
• Støle, Hanne Stavenes; Varsi, Cecilie; Eide, Hilde; Kristjansdottir, Olöf Birna; Børøsund, Elin & Waxenberg, Lori B. [Vis alle 13 forfattere av denne artikkelen] (2022). EPIO studien - Å leve godt med langvarige smerter. Fulltekst i vitenarkiv
• Støle, Hanne Stavenes; Bostrøm, Katrine; Varsi, Cecilie; Eide, Hilde; Kristjansdottir, Olöf Birna & Børøsund, Elin [Vis alle 14 forfattere av denne artikkelen] (2022). EPIO - Å leve godt med langvarige smerter. Fulltekst i vitenarkiv
• Solem, Ingrid Konstanse Ledel; Bostrøm, Katrine; Støle, Hanne Stavenes; Nes, Lise Solberg; Varsi, Cecilie & Eide, Hilde [Vis alle 13 forfattere av denne artikkelen] (2022). Smertemestringsstudien EPIO. Fulltekst i vitenarkiv
• Årnes, Anders; Fjeld, Mats Kirkeby; Wilsgaard, Tom; Morseth, Bente; Hopstock, Laila Arnesdatter & Graven-Nielsen, T [Vis alle 10 forfattere av denne artikkelen] (2022). The relationship between physical activity and cuff-pressure algometry tolerance: The Tromsø Study 2015-2016. Fulltekst i vitenarkiv
• Nes, Lise Solberg; Varsi, Cecilie; Eide, Hilde; Kristjansdottir, Olöf Birna; Børøsund, Elin & Waxenberg, Lori B. [Vis alle 14 forfattere av denne artikkelen] (2022). EPIO - en app for de som lever med langvarige smerter. Fulltekst i vitenarkiv
• Nes, Lise Solberg; Varsi, Cecilie; Eide, Hilde; Kristjansdottir, Olöf Birna; Waxenberg, Lori B. & Schreurs, Karlein M.G. [Vis alle 10 forfattere av denne artikkelen] (2021). Living Well With Chronic Pain: Using Person-centered eHealth Design to Support Self-management. Fulltekst i vitenarkiv
• Vambheim, Sara Magelssen; Stubhaug, Audun; Ljoså, Tone Marte & Granan, Lars-Petter Ness (2021). S. Vambheim og medarbeidere svarer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(18). doi: 10.4045/tidsskr.21.0819. Fulltekst i vitenarkiv
• Stubhaug, Audun; Ljoså, Tone Marte; Granan, Lars-Petter & Vambheim, Sara Magelssen (2021). Opioidkrisen kan avblåses. doi: 10.4045/tidsskr.21.0621. Fulltekst i vitenarkiv
• Solem, Ingrid Konstanse Ledel; Varsi, Cecilie; Heldal, Karina; Kristjansdottir, Olöf Birna; Eide, Hilde & Mirkovic, Jelena [Vis alle 18 forfattere av denne artikkelen] (2019). Brukernes behov og ønsker i utviklingen av en e-helseintervensjon for personer med langvarig smerte. Fulltekst i vitenarkiv
• Varsi, Cecilie; Nes, Lise Solberg; Kristjansdottir, Olöf Birna; Stenberg, Una; Zangi, Heidi Andersen & Kelders, Saskia M [Vis alle 14 forfattere av denne artikkelen] (2019). Implementeringsstrategier benyttet ved implementering av e-helseløsninger for pasienter med kronisk sykdom. Fulltekst i vitenarkiv
• Varsi, Cecilie; Nes, Lise Solberg; Kristjansdottir, Olöf Birna; Stenberg, Una; Zangi, Heidi Andersen & Kelders, Saskia M [Vis alle 14 forfattere av denne artikkelen] (2019). Implementering av e-helseløsninger for pasienter med kronisk sykdom - Review av implementeringsstrategier. Fulltekst i vitenarkiv
• Solem, Ingrid Konstanse Ledel; Varsi, Cecilie; Heldal, Karina; Tørring, Hilde Eide; Kristjansdottir, Olöf Birna & Mirkovic, Jelena [Vis alle 18 forfattere av denne artikkelen] (2019). User identified needs and requirements in the development of an eHealth pain management intervention. Fulltekst i vitenarkiv Vis sammendrag

  Background: A growing body of evidence supports the efficacy of eHealth interventions in coping with a variety of illnesses and disorders, including short- and long-term pain conditions. The efficacy and continued use of eHealth treatment programs depend not only on content and technology but also on the patients’ motivation, acceptance and adherence. Despite interest from patients, existing chronic pain eHealth studies have experienced high attrition rates. New interventions are necessary, focusing specifically on patients’ needs, perspectives, expectations and context of use. Aim: The present study seeks to identify the unmet informational and support needs of patients with chronic pain, and to investigate how an eHealth intervention can be designed to address these needs. In doing this, caregivers experiences and needs are included. Users’ requirements for functionality and design are also explored. Method: Individual interviews were conducted with patients living with different chronic pain conditions (N=15; e.g., neuropathic pain, musculoskeletal pain and rheumatic pain). Treatment backgrounds varied, ranging from general practitioners’ visits and physical therapy in primary health care to more specialized treatments in secondary health care. Caregivers (spouses; N=5) were also interviewed to provide insight into caregivers’ experiences, needs and perspectives and to gain a deeper understanding of the patient group. Results: Interviews provided insight into needs and wishes of patients and their caregivers living with chronic pain related to everyday life and coping. The need for mastery, normalization and activity pacing were highlighted. Furthermore, the need for a positive distraction, especially in relation to high pain levels, stressful situations and struggles with sleep were expressed by both groups. Preferences as to design of an eHealth tool, type of platform and privacy issues were identified, showing accessibility to be a key factor for user adoption. Conclusions: The study provides important knowledge about the everyday needs of patients with chronic pain and their preferences in relation to a digital pain management intervention. Possible areas where an eHealth intervention might support existing treatments, such as learning and mastery courses, are also identified. Results give direction for further development and prototyping of an intervention that will ultimately be tested in a randomized controlled trial.

Se alle arbeider i NVA