Abstract for the special issue

Adverse events in treatment of non-specific low back pain: a systematic review (Authors not available at SASP 2022)

Lajord, Even

Dalsgaard Kusk, Morten, Bo Rønsholdt, Peter

Aalborg University, Aalborg, Denmark

Reviews (Topical, Systematic, or Meta-analysis)

Objective: The aim of this systematic review is to evaluate adverse events from recommended therapies and interventional strategies for the treatment of non-specific low back pain.

Methods: An electronic search was conducted in PubMed, EMBASE, and Cochrane Library, including systematic reviews only. Reviews were considered eligible if they included; (1) participants with non-specific low back pain (2) recommended interventions for non-specific low back pain and (3) explicitly mentioned adverse events. Two authors independently screened systematic reviews for inclusion. Disagreements were resolved by consulting a third author. Data was extracted directly from the randomized controlled trials if reported insufficiently in the systematic reviews. Two authors independently assessed quality using AMSTAR-2.

Results: We included 36 systematic reviews. Only four of the 36 included systematic reviews reported adverse events sufficiently. Data was extracted and analyzed directly from 130/464 RCTs in the remaining 32 systematic reviews. From the non-pharmacological interventions, exercise had the highest percentage of non-serious adverse events, 9%, and psychological interventions had the highest percentage of serious adverse events, 0.5%. Surgical interventions were associated with a relatively high percentage of non-serious adverse events, 36.3%, and the highest percentage of serious adverse events, 3.2%. From the pharmacological interventions, opioids had the highest percentage of non-serious and serious adverse events with 92.9% and 2.4% respectively.

Conclusion: There is an urgent need for systematic reporting of adverse events, particularly in non-pharmacologic interventions. Pharmacological and surgical interventions are associated with a substantial risk of harm and should be carefully considered in the management of non-specific low back pain.

Mapping out the gaps of the management for chronic musculoskeletal pain: a systematic review of systematic reviews (#22)

Lyng, Kristian Damgaard¹ Djurtoft, Chris¹, Bruun, Malene¹, Christensen, Mads¹, Laurtisen, Rikke², Larsen, Jesper Bie¹, Birnie, Kathryn³, Stinson, Jennifer³, Hoegh, Morten¹, Palsson, Thorvaldur¹, Olesen, Anne Estrup¹, Arendt-Nielsen, Lars¹, Ehlers, Lars⁴, Fonager, Kristen², Jensen, Martin Bach¹, Würtzen, Hanne⁵, Poulin, Patricia⁶, Handberg, Gitte⁷, Ziegler, Connie⁸, Moeller, Lars⁹, Olsen, Judi¹⁰, Heise, Lotte¹¹, Rathleff, Michael Skovdal¹

¹Aalborg University, Klarup, Denmark

²Aalborg University Hospital, Aalborg, Denmark

³University of Calgary and University of Toronto, Canada

⁴Nordic Institute of Health Economics (NIHE), Aalborg Øst, Denmark

⁵Department of Neuroanaesthesiology, The Multidisciplinary Pain Centre, Rigshospitalet, Copenhagen, Denmark

⁶Department of Psychology, The Ottawa Hospital, Ottawa, Ontario, Canada, Ottawa, Canada

⁷Pain Center, Odense University Hospital, Odense, Denmark, Odense, Denmark

⁸Gigtforeningen, Copenhagen, Denmark

⁹FAKS, Copenhagen, Denmark

¹⁰Fibromyalgi.dk, Copenhagen, Denmark

¹¹Danish Broadcast Cooperation, Copenhagen, Denmark

Reviews (Topical, Systematic, or Meta-analysis)

Background: Evidence and gap map (EGM) is a method to guide future research and draw attention to potential gaps in research. EGMs aim to assess the quality of the current literature within a specific field and furthermore, to identify the existing gaps. No EGMs exist to guide chronic musculoskeletal (MSK) pain in adults and therefore this study was initiated to create an EGM of interventions used in chronic MSK pain.

Methods: We performed a systematic review of systematic reviews based on randomised control trials investigating treatment interventions for chronic MSK pain. All included reviews were published in peer-reviewed journals and were searched through four different databases (Embase, PubMed, the Cochrane Library, and PsycINFO). All reviews were assessed using the critical appraisal tool, AMSTAR-II. Information regarding interventions was extracted and categorised into either physical, psychological, pharmacological, education/advice, interdisciplinary, or other. Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations was used to categorise the outcomes used in the included reviews.

Results: 4299 systematic reviews were screened for eligibility and of these, 457 were included. Of these, 15% were rated high-quality, 10% were rated moderate quality, 25% were rated low quality and 50% were rated critically low quality. In 80% of the reviews, physical interventions were used, followed by education/advice in 20% of the reviews. 97% of the reviews included used pain intensity as an outcome and 87% used physical functioning as an outcome. The EGM will be visualised for readability and to quickly get an overview of the existing gaps.

Conclusion: The results from this study highlight the general evidence quality of this field and highlight the gaps of the current literature. This information can be used for policy-making and for direction future research.

Paracetamol in the management of fever and pain associated with covid-19 and post vaccination symptoms in children (#43)

Bhagat, Preeti Kachroo¹ Siddiqui, Kamran Hasan¹, Della Pasqua, Oscar²

¹GlaxoSmithKline Consumer Healthcare Pte. Ltd, Singapore, Singapore

²GlaxoSmithKline, Brentford, United Kingdom

Reviews (Topical, Systematic, or Meta-analysis)

Aim: Despite frequent use of paracetamol in children for management of fever and mild-to-moderate pain, there is unclear clinical literature/guidance regarding its use in COVID-19 infection or post-COVID-19 vaccination symptoms management. This review collates information available from various guidelines, government sites and published studies on the stated use of paracetamol in pediatric population.

Methods: Literature search was carried out up to June 16, 2022 using the keywords “COVID-19” or “SARS-CoV-2” or “Corona virus” and “children” or “pediatric” up to 18 years and “paracetamol” or “acetaminophen” and “vaccination” in electronic databases (MEDLINE, PUBMED) and guidelines.

Results: Thirty-six relevant articles include 21 reviews/originals,14 guidelines and one FDA briefing document. Children infected with COVID-19 remain mostly asymptomatic or mildly symptomatic. Public health authorities and clinical guidelines from different countries recommend paracetamol at dose of 10–15 mg/kg (liquid or tablet) as required to treat fever and pain like symptoms in children with COVID-19. Studies have also reported paracetamol as most prescribed treatment for these indications. FDA has approved the COVID-19 vaccine for age group 5 years and above with a recent recommendation on inclusion of 6 months-5 years age group. In children with post-vaccination symptoms like fever and pain, clinical and public guidelines from nine countries recommend paracetamol as therapeutic approach, though data is scarce. To date, three RCTs investigating COVID-19 vaccine in children (6 months and above) have mentioned paracetamol for post-vaccination symptomatic relief of pain and fever. Reviewed literature also suggests paracetamol use for treatment (rather than prevention) of symptoms after vaccination appears to be effective, without affecting the response to vaccination.

Conclusion: Paracetamol is recommended treatment to relieve fever, discomfort and mild to moderate pain in children with COVID-19 infection and post vaccination. Due to paucity of data, further studies are needed in children to establish the role of paracetamol in COVID-19.

Herbals for pain management: A growing consumer acceptance of herbals and impact of topical herbals on sensorial benefits in pain (#47)

Bhagat, Preeti Kachroo¹ Deutsch, Daniela², Warren, Rebecca³

¹GlaxoSmithKline Consumer Healthcare Pte. Ltd, Singapore, Singapore

²GlaxoSmithKline Consumer Healthcare, Munich, Germany

³University of New South Wales, Sydney, Australia

Reviews (Topical, Systematic, or Meta-analysis)

Aims: Pain is a commonly experienced condition that affects quality of life. We present the outcomes of two surveys conducted by GSK to understand different approaches people consider for pain management and literature search to identify the potential of common topical herbs as options in pain management.

Method: The Global Pain Index (Survey-1), an online quantitative survey was conducted across 19 countries (N=19,000). A second qualitative study, Pharmacy Research Germany (Survey-2) was conducted on 30 German pharmacists to evaluate market perception about topical herbals. Following the survey outcomes, an open literature search was conducted in PubMed, Embase and Grey literature from Monographs, Physicians-Desk-Reference’s to evaluate effects of topical herbs on sensorial attributes of pain.

Results: Survey-1 revealed a growing interest of pain sufferers in alternative therapies. 33% consumers seek alternative therapies while purchasing pain medications. Different surveyed geographies highlighted different percentages of pain sufferers likely to take herbal remedies like: Middle East (20%; N=914), Germany (13%; N=904), Australia (5%; N=846), Italy (4%; N=925).

Survey-2 reveals increasing demand for topical herbal remedies for pain management which may be used as first-choice or add-on therapy owing to their safety profile and sensorial benefits.

The surveys showed topical herbals as preferred alternative treatment. The literature searches revealed beneficial effects achieved by distracting the brain through temporary hot or cold sensations (Gaultheria procumbens, Arnica montana, Mentha piperita); skin moisturizing and healing properties (Aloe-vera, Centella asiatica); refreshing and pleasant odors (Mentha piperita, Gaultheria procumbens); alleviating tenderness and soothing effect (Aesculus hippocastanum).

This potential of topical herbals in modifying pain perception through sensorial attributes could improve pain management.

Conclusion: The surveys showed growing interest of pain sufferers in alternative solutions like topical herbals. Six topical herbs listed may provide beneficial sensorial effects and can be considered as first-choice treatment among mild-to-moderate pain sufferers seeking natural solutions.

Assessment of pain in chemotherapy induced peripheral neuropathy (CIPN) tools – a bag of mixed apples (#51)

Gehr, Nina Lykkegaard¹ Ventzel, Lise², Finnerup, Nanna Brix³

¹Aarhus University, Aarhus N, Denmark

²Vejle Hospital, University Hospital of southern Denmark, Denmark

³Aarhus University, Aarhus, Denmark

Reviews (Topical, Systematic, or Meta-analysis)

Aims: Neuropathic pain due to chemotherapy-induced peripheral neuropathy (CIPN) is a well-known adverse effect with major impact on cancer survivors’ quality of life and function of daily living. It is the only symptom in CIPN that might be improved with medication and therefore a clinically relevant symptom to evaluate. Our aim was to examine commonly used assessment tools for CIPN to assess if and how they include pain assessment.

Methods: Reviews and a database search were used to identify CIPN assessment tools used in clinical settings.

Results: The search revealed 35 assessment tools. Twelve tools were shorter versions derived from other tools leaving 23 different assessment tools.We identified 15 different patient reported outcome (PROs) questionnaires of which 9 include one or more questions concerning pain. One includes a question about pain in general, four specifies pain in the hands or feet, one nerve pain and one pain localized to muscle and joints. Three questionnaires restrict the question to pain with specific characteristic (one stabbing, burning, stinging, or cramping another only assessed shooting or burning pain and a third restricting it to tingling pain). Seven tools were common toxicity scores, of which some are used frequently in the clinic. All 7 use the term paresthesia without further definition or explanation of the term. One includes pain, but as a term of progression from paresthesia. One tool was a neurological composite scale including both clinical findings and sensory symptoms of which one is pain not further specified but graded according to distribution on lower or upper extremities.

Conclusion: Despite its significant impact, most CIPN tools do not include questions about pain, and some restrict reporting of pain to pain with specific characteristics. In addition, type, distribution and characteristics of pain are not evaluated.

Tendon pain – what are the mechanisms behind it? (#64)

Peterson, Magnus¹ Alim, Abdul¹, Pejler, Gunnar¹, Ackermann, Paul²

¹Uppsala University, Uppsala, Sweden

²Karolinska University Hospital, Stockholm, Sweden

Reviews (Topical, Systematic, or Meta-analysis)

Aims: To present the pathophysiological mechanisms of action, pain receptors and mediators underlying the development of chronic tendon pain that have recently been identified. This new understanding may allow us to develop new targeted treatments for managing tendon pain.

Methods: Management of chronic tendon pain is difficult and controversial. This is due to poor knowledge of the underlying pathophysiology of chronic tendon pain, priorly known as tendinitis but now termed tendinopathy. The objective of this topical review was to synthesize evolving information of mechanisms in tendon pain, using a comprehensive search of the available literature on this topic.

Results: This review found no correlations between tendon degeneration, collagen separation or neovascularization and chronic tendon pain. The synthesis demonstrated that chronic tendon pain, however, is characterized by excessive nerve sprouting with ingrowth in the tendon proper, which corresponds to alterations observed also in other connective tissues of chronic pain conditions. Healthy, pain-free tendons are devoid of nerve fibers in the tendon proper, while innervation is confined to tendon surrounding structures, such as sheaths. Chronic painful tendons exhibit elevated amounts of pain neuro-mediators, such as glutamate and substance P as well as up-regulated expression and excitability of pain receptors, such as the glutamate receptor NMDAR1 and the SP receptor NK1, found on ingrown nerves and immune cells. Increasing evidence indicates that mast cells serve as an important link between the peripheral nervous system and the immune systems resulting in so called neurogenic inflammation.

Conclusion: Chronic painful tendons exhibit 1) protracted ingrowth of sensory nerves 2) elevated pain mediator levels and 3) up-regulated expression and excitability of pain receptors, participating in 4) neuro-immune pathways involved in pain regulation. Current evidence-based treatments for chronic tendon pain include eccentric exercises and extracorporeal shockwave, which both target peripheral neoinnervation aiming at nerve regeneration.

Reported outcomes in interdisciplinary pain treatment: An overview of systematic reviews and meta-analyses of randomised controlled trials (#66)

Dong, Huan-Ji¹ Gerdle, Björn², Dragioti, Elena²

¹Linköping University, Linköping, Sweden

²Pain and Rehabilitation Center, Linköping University, Sweden, Linköping, Sweden

Reviews (Topical, Systematic, or Meta-analysis)

Aim: There is considerable diversity of outcome selections and methodologies for handling the multiple outcomes across all systematic reviews (SRs) of Interdisciplinary Pain Treatment (IPT) due to the complexity of IPT. This overview systematically collates the reported outcomes and measurements of IPT across published SRs and identifies the methodological characteristics. Additionally, we provide some suggestions on framing the selection of outcomes and on conducting SRs of IPT.

Methods: Three electronic databases (PubMed, Cochrane Library, and Epistemonikos) and the PROSPERO registry for ongoing SR were supplemented with hand-searching ending on 30 September 2021.

Results: We included 18 SRs with data on 49 007 people from 356 primary randomised controlled trials (RCTs); eight were followed by meta-analysis and ten used narrative syntheses of data. For all the SRs, pain was the most common reported outcome (72%), followed by disability/functional status (61%) and working status (61%). Psychological well-being and quality of life were also reported in half of the included SR (50%). The core outcome domains according to VAPAIN, IMMPACT, and PROMIS were seldom met. The methodological quality varied from critically low to moderate according to AMSTAR2. The AMSTAR2 rating was negatively correlated to the number of outcome domains in PROMIS, and VAPAIN was positively correlated with IMMPACT and PROMIS, indicating the intercorrelations between the reported outcomes.

Conclusions: This systematic overview showed wide-ranging disparity in reported outcomes and applied outcome domains in SRs evaluating IPT interventions for chronic pain conditions. The intercorrelations between the reported outcomes should be appropriately handled in future research. Some approaches are discussed as well.

Author’s statement: The manuscript has just been accepted by J of Pain Res (2022-06-10), but not get published yet.

Nurses’ attitudes and knowledge toward pain assessment in older adults with dementia: A literature review (#78)

Jonsdottir, Thorbjorg

University of Akureyri, Akureyri, Iceland

Reviews (Topical, Systematic, or Meta-analysis)

Aims: The aim of this integrative review is to examine the attitudes and knowledge of nurses regarding the assessment and treatment of pain in elderly patients with dementia.

Method: A systematic reference search was performed in the electronic databases, Web of Science, MEDLINE, Scopus, ProQuest, PubMed and EBSCOhost for articles specifically focusing on nurses’ knowledge and attitudes towards pain assessment in older patients with dementia, published from January 2008 to December 2018. PRISMA guidelines were used to search and select research.

Results: Ten studies met all the search criteria including a total of 407 nurses working in nursing homes, hospitals, and hospices in five countries: United Kingdom, USA, Australia, Sweden, and South Korea. The main theme in research findings was that assessment and treatment of pain in elderly people with dementia is a complex process with many uncertainties. Pain assessment was often based on a subjective assessment of the client’s behaviour, e.g., agitation, without the use of specialized pain-assessment instruments. It was also common that “undesirable” behavioural symptoms were treated with psychotropic drugs without examining whether pain was a possible cause. Pain assessment and treatment was therefore often ineffective. Participants often felt that they lacked time, knowledge, and training in assessing and managing their clients’ pain. Uncertainty about opioid use as well as lack of understanding and support from doctors were also important barriers to effective pain assessment and management among patients with dementia.

Conclusion: Patients with dementia are at greater risk of experiencing underassessment, undertreatment, and delayed treatment of pain due to nurses’ knowledge deficits and uncertainty in the decision-making process. It is important to increase the knowledge and training of both nurses and doctors working among the elderly with dementia, as well as to strengthen the collaboration of these health professionals.

Does health behaviour mediate the effect of depressive symptoms on health-related quality of life? A cross-sectional analysis of breast cancer survivors with persistent pain (#2)

Aho, Tommi¹ Harno, Hanna², Sipilä, Reetta², Kalso, Eija³

¹University of Helsinki, Turku, Finland

²Helsinki University Hospital, Helsinki, Finland

³University of Helsinki, Helsinki, Finland

Clinical Research

Aims: Depressive symptoms are common among breast cancer (BC) survivors affecting on patients’ health-related quality of life (HrQoL) and long-term adjustment of persistent pain. Unfavorable health behaviours, such as smoking, are known to have an association with both depression and pain. We aimed to study the mediating role of various health behaviours and serum biomarkers between depressive symptoms and HrQoL in BC survivors with persistent pain.

Method: We studied depressive symptoms (assessed by Beck’s Depression Inventory, BDI) and physical and mental dimensions of HrQoL (assessed by Short-Form 36 -survey, SF-36) in 306 BC survivors who reported at least mild persistent pain (assessed by Brief Pain Inventory, BPI) at any site of the body. Smoking habits, alcohol consumption, serum triglyceride, low-density lipoprotein (LDL) and HbA1c concentrations, and body mass index (BMI) were assessed and used as mediators. We used single mediation modelling, by using the PROCESS add-on V.2.16.1 in SPSS.

Results: Significant correlation was found for smoking habits, serum triglycerides, and BMI on depressive symptoms and dimensions of HrQoL. The total effect of depressive symptoms on physical (β_total=-1.157, p<0,001) and mental HRQoL (β_total=-2.083, p<0,001) was significant. Only smoking habits mediated the negative effect of depressive symptoms on physical HrQoL. This association was explained by both cognitive-emotional (indirect effect:-0.183, CI_95%:-0.363 to -0.045) and somatic (indirect effect:-0.207, CI_95%:-0.457 to -0.036) depressive symptoms.

Conclusions: Smoking habits associate with various unfavorable outcomes on persons’ health. Comorbid smoking in chronic pain patients with symptoms of depression may convey the negative effects of depression in HrQoL. Both, cognitive-emotional and somatic symptoms of depression, should be considered for clinical interventions to improve overall wellbeing and HrQoL in BC survivors with persistent pain. The result may provide new insights for targeted smoking reduction interventions beside of treatment of depression in patients with persistent pain.

The Danish translation and validation of the Self-Compassion Scale (#7)

Jarløv, Therese T

Larsen, Dennis B., Petrini, Laura

Aalborg University, København, Denmark

Clinical Research

Aim: Mental well-being and self-compassion are increasingly acknowledged as important components in the chronic pain experience. Therefore, the 26-item Self-Compassion Scale (SCS) may prove to be useful in chronic pain management. This study aimed to translate and validate the 26-item SCS from English to Danish and evaluate its psychometric properties. To assess its value in future clinical settings the SCS score was compared between a chronic non-malignant pain population and a Danish background population.

Method: The dual panel approach was applied for linguistic and cross-cultural translation. Participants were recruited through social media and multidisciplinary pain centers. The Exploratory Factor Analysis (EFA) was used to investigate the factor structure of the SCS. To assess construct validity of the translated SCS, a model fit analysis was conducted through the Confirmatory Factor Analysis (CFA). Intraclass Correlation Coefficient (ICC) was used to verify test-retest reliability.

Results: Thirty-four individuals participated in the dual panel and verified that the Danish translation reflected the original English version. The test-retest (two-weeks) sample included 60 individuals which demonstrated an estimated average ICC of 0.889 with a 95% confidence interval [95% CI 0.815 to 0.934] and Smallest Detectable Change (SDC) of 1.16. Hence a non-clinically relevant difference was found in SCS score between the background population (M=[3.25], SD=[0.69]) and chronic pain patients (M=[2.91], SD=[0.66]); t(df) = [6.483(759)], p=[0.000]. A total of 761 individuals were included in the CFA, which validated the SCS through an acceptable model fit based on a six-factor construct.

Conclusion: The SCS was successfully translated through the dual panel approach and validated by the CFA, where the original six-factor construct in the SCS was supported. The psychometric properties verified the reliability of the Danish version for assessment of Self-Compassion. Finally, SCS may contribute to increased awareness of the influence of mental health on various treatment intervention outcomes.

The unique contribution of psychological flexibility to functioning in patients with chronic cancer-related pain (#12)

Duarte, Joana¹ Sean, Perrin¹, McCracken, Lance², Björkstrand, Frida¹

¹Lund University, Lund, Sweden

²Uppsala University, Uppsala, Sweden

Clinical Research

Aims: Cancer-related pain has been associated with greater psychological distress among patients with a cancer diagnosis (current or previous), although the relationships among pain and these outcomes remains poorly studied. The current study aims to improve our understanding of the relation between chronic cancer-related pain and functioning by testing potential theoretical mechanisms as proposed by the psychological flexibility model (pain acceptance, mindfulness, committed action). We hypothesised that psychological flexibility would predict higher levels of quality of life, and lower levels of pain interference, depression, and fatigue, after other relevant predictors were taken into account.

Method: This cross sectional study included 246 adult patients with a cancer diagnosis (current or previous) living in Sweden. Eligible participants participated in an online survey assessing cancer-related pain, psychological inflexibility, pain-related functional impairment, psychological distress, and social stigma through self-reported questionnaires.

Results: Moderate and strong correlations were found between all outcomes. In regression analyses, the three variables representing psychological flexibility accounted for significant variance in all the outcomes (pain interference, depression, health-related quality of life, and fatigue), over and above pain intensity and social stigma. Of the psychological flexibility variables, pain acceptance emerged as a particularly important predictor of all the outcomes.

Conclusion: Identifying individual difference variables that mitigate pain, disability, and psychological distress may contribute to the development of more effective psychosocial treatments aimed at facilitating adaptation and improving the quality of life of cancer patients who have chronic pain. Our results suggest that psychological flexibility could be such a variable and potentially an important place to intervene clinically in order to counteract the negative effects of cancer-related pain.

Neck pain characteristics and inflammatory biomarkers in plasma among forklift truck operators (#34)

Ghafouri, Bijar¹ Rolander, Bo², Gerdle, Björn¹, Wåhlin, Charlotta¹

¹Linköping University, Linköping, Sweden

²Jönköping Hospital, Jönköping, Sweden

Clinical Research

Aims: The aim of this study was to investigate neck pain characteristics and movements among forklift truck operators (FLTOs) compared with healthy subjects. Further this study aims to analyze inflammatory biomarkers in plasma from FLTOs with and without reported neck pain and healthy controls and their correlations to the neck pain characteristics.

Methods: Male FLTOs (n=23) were recruited among the employments in a warehouse and healthy age and sex matched subjects (n=24) were recruited. The inclusion criteria for FLTOs were that they should operate reach decker and/or counterbalanced tilting mast trucks. All participants answered questionnaire covering demographics, pain, health, anatomical spreading, and psychological distress. Measurement of pain sensitivity, neck and shoulder strength, neck flexion and range of motion were performed. Blood samples were collected and analyzed for plasma inflammatory proteins using a panel of 72 cytokines and chemokines (Meso Scale Discovery, Maryland, USA).

Results: In FLTOs 82% reported musculoskeletal symptoms in at least one body part during the past 7 days. The FLTOs most often reported symptoms in the neck (30%), shoulders (26.3%), and lower back (26.3%). Pain and discomfort that most often prevented completing activities were in the neck (20%), lower back (31.6%), and hip (26.9%). There were significant differences in pain intensity between FLTOs and CON. FLTOs reported higher anxiety (p<0.05) compared to healthy controls. The pressure pain thresholds were lower in FLTOs compared to healthy controls.

A significant OPLS-DA model (CV-ANOVA p=5.75e-05) could discriminate FLTOs from CON based on nine inflammatory proteins. Levels of M-CSF, IL-16, MIP-1α and IL-17A/F were higher in FLTOs compared to CON. There were 29 proteins that in a multivariate analysis correlated to pain intensity in FLTOs.

Conclusions: Using both self-reported measures and objective plasma biomarkers can be useful to understand the pathophysiological mechanisms behind work related neck and shoulder pain.

Immune cell skin infiltration in type 1 diabetes and diabetic polyneuropathy (#36)

Hu, Xiaoli¹, Karlsson, Pall⁵ Buhl, Christian¹, Schousboe, Karoline², Mizrak, Hatice Isik³, Kufaishi, Huda³, Jensen, Troels Staehelin¹, Hansen, Christian Stevns³, Yderstræde, Knud Bonnet, Nyengaard, Jens Randel

¹Aarhus University, Aarhus, Denmark

²Odense University Hospital, Odense, Denmark

³Steno Diabetes Center Copenhagen, Copenhagen, Denmark

⁵Aarhus University, Aarhus, Denmark

Clinical Research

Background: Diabetic polyneuropathy (DPN) is a common disabling complication of diabetes that can either be painless or painful, but the mechanisms behind development of neuropathic pain are not fully understood with the consequence that treatment is suboptimal. Evidence is increasing that infiltration of inflammatory components may play a role in the onset of neuropathic pain. This study assessed the relationship between two distinct immune cells (Langerhans cells (LC) and macrophages) and presence and severity of neuropathic pain in patients with type 1 diabetes (T1D), with and without neuropathy, with and without pain.

Method: All patients underwent detailed phenotyping, including a structured clinical examination, quantitative sensory testing, electrophysiology, autonomic testing and a skin biopsy. Skin biopsies from all patients without DPN and with definite painful and painless DPN (according to the Toronto consensus panel criteria) and healthy controls without diabetes were included. Skin infiltrating LC and macrophages were visualized and analyzed using advanced immunohistological staining and stereological methods. LC density (number/volume) was quantified, and a novel grading system was developed to semi-quantify the degenerative morphology of somata and processes in epidermal LCs. The degree of infiltration of dermal macrophages was estimated by counting the occupation of Iba1-labelled cells in the dermis.

Results: 171 patients with T1D (including 52 patients with painful DPN) and 51 healthy controls were recruited prospectively. Quantification is still ongoing and results will be presented at the conference, including correlational analysis between the inflammatory biomarkers and presence of neuropathy and neuropathic pain. Preliminary results indicate altered levels of LC degeneration in terms of density, soma size and process structure, as well as IbA1⁺ macrophage infiltration in the skin of patients with painful DPN.

Conclusion: The study will increase our knowledge about the remobilization of inflammatory factors in patients with T1D, with and without neuropathy, with and without pain.

Identification and quantification of nociceptive Schwann cells in mice and in patients with type 1 diabetes, with and without neuropathic pain (#37)

Hu, Xiaoli¹, Karlsson, Páll⁴ Buhl, Christian, Schousboe, Karoline², Mizrak, Hatice Isik⁵, Kufaishi, Huda⁵, Jensen, Troels Staehelin¹, Hansen, Christian Stevns⁵, Yderstræde, Knud Bonnet², Agarwal, Nitin³, Zhang, Ming-Dong, Ernfors, Patrik², Kuner, Rohini³, Nyengaard, Jens Randel⁴

¹Aarhus University, Aarhus, Denmark

²Odense University Hospital, Odense, Denmark

³Heidelberg University, Heidelberg, Germany

⁴Aarhus University, Aarhus, Denmark

⁵Steno Diabetes Center Copenhagen

Clinical Research

Background: The mechanisms behind neuropathic pain in diabetes are not fully understood. Recently, skin nociceptive Schwann cells (SC) were introduced for the first time in mice, a glia cell that is believed to be involved in pain initiation. However, the morphology of SC has not been studied before. In these studies, we quantified SC density first in mice and then in patients with type 1 diabetes (T1D).

Method: 3-mm skin biopsies from both T1D STZ-mouse models (hyper- and hyposensitive and age-matched controls) and carefully phenotyped T1D patients (with and without neuropathy, with and without pain) and healthy controls were taken and immunostained with relevant antibodies to visualize the SC.

Results: A total of 24 mice and 120 human participants were included in the studies. The animal study showed that hypersensitive (painful) diabetic mice had decreased nociceptive SC density (P=0.0023), but normal intraepidermal nerve fibre density (IENFD) compared to their age-matched control group, while the hyposensitive (painless) diabetic mice had a reduction in IENFD but no difference in nociceptive SC density (p>0.05). The patient biopsies have been evaluated, but the analysis is still ongoing. Results of nociceptive SC density, IENFD, dermal SC and nerve fibre density in each patient group will be presented at the conference.

Conclusion: The studies provide a detailed description of how to quantify the newly reported nociceptive SC. At least in the STZ animal model of painful DPN, the nociceptive SC deteriorate before the nerve fibres do, indicating that they are involved in development of neuropathic pain.

Experiences from patients with chronic pain and obesity: pain leads to excess weight and affects their ability to make lifestyle changes. A qualitative study (#45)

Storm, Elin¹ Bendelin, Nina¹, Dong, Huan-Ji¹

¹Linköping University, Linköping, Sweden

Clinical Research

Aims: Quantitative studies show an interrelated relationship between pain and excess weight. However, knowledge about patients’ experiences of living with chronic pain and co-morbid obesity is scarce. This qualitative study aimed to expand the understanding of patients’ perspectives on how chronic pain and obesity influence each other and how the two conditions affect patients’ ability to make lifestyle changes.

Method: A purposive sample of adults with Body Mass Index (BMI) ≥ 30 kg/m² who had participated in an interdisciplinary pain rehabilitation program (IPRP) were interviewed individually. A semi-structured interview guide was used to explore participants’ experiences of chronic pain, obesity and lifestyle changes in the context of IPRP. The transcribed interviews were analyzed using content analysis with an inductive approach.

Results: Sixteen adults (11 female) aged 28–63, BMI ≥30–43 kg/m², participated. Four core categories covered the topics: “Relationship between pain and weight”, “balancing the daily energy”, “emotional factors of pain when making lifestyle choices” and “the physical experience of pain when making lifestyle choices”. Most participants were aware of pain as having a negative impact on weight control, but they expressed uncertainty towards whether weight affected pain. The participants experienced that pain reduced their energy, and caused a need for activity balance. Fear of pain restricted physical activity and a need for enjoyment caused unhealthy dietary choices. Pain could both be a motivation for exercise and weight loss or the lacking key to engage in a healthy lifestyle.

Conclusion: Patients with chronic pain and obesity experienced only a unilateral relationship between excess weight and pain, where pain led to excess weight. Chronic pain played a complex role when the patients made lifestyle choices. These findings are important for clinicians to adapt patient-tailored IPRPs with focus on patient education as well as strategies for making successful lifestyle changes.

Experiences and usability of a digital website containing research-based knowledge and tools for pain self-management: preliminary results from a study in people living with high-impact chronic pain (#46)

Bendix, Laila¹, Vægter, Henrik Bjarke¹ Fuglsang, Kira Søndberg¹, Jäger, Madalina², Lærkner, Eva²

¹Odense University Hospital, Odense, Denmark

²University of Southern Denmark, Odense, Denmark

Clinical Research

Aims: An increasing proportion of people suffer from chronic pain. Pain science education re-conceptualizing the threat value of chronic pain combined with self-management strategies is a well-documented intervention. In a collaboration between pain specialists and a large user panel the freely available website Smerteinfo.dk (eng. Pain info) has been developed. The website contains research-based knowledge for people with chronic pain, focusing on enabling them to actively cope with pain. The aim of this study was to explore experiences and usability of Smerteinfo in people living with high-impact chronic pain.

Methods: Patients referred to the Pain Center at the University Hospital Odense after January 1st 2022 electronically received a letter inviting them to visit selected articles on Smerteinfo, while on waiting list. Three months later a questionnaire evaluating the experiences and usability of Smerteinfo was sent to the patients, asking to what degree they had gained a better understanding of their pain, and whether Smerteinfo had been helpful in implementing changes to their daily life. Further, how likely they were to use the website in the future and to recommend it to a friend.

Results: So far, 52 patients (38F) with mean age 53.5 years (SD 14.7) have responded to the questionnaire, with 27 reporting having visited the site. Of those visiting the site, a majority found that the site was relevant to them (62.9%) to a high or very high degree. 40.7% reported having made changes in their daily life and 50% experienced that they were better able to manage their pain to some or a large degree. 42.3% would likely visit the site again while 50% would likely recommend the site to others.

Conclusions: These preliminary results suggest that a freely available website can support some patients in making active changes in their daily life.

Hypocapnia in people with fibromyalgia (#56)

Jonsson, Kent, Pikwer A, Olsson E, Peterson M.

Department of Public Health and Caring Sciences, Uppsala, Sweden

Clinical Research

Aims: The purpose of this study was to investigate whether people with fibromyalgia (FM) have changes in arterial blood gas pressure and compare with healthy controls. A secondary aim was to investigate the influence of various physical and psychological symptoms on these blood gases.

Method: Thirty-six women diagnosed with FM and 36 healthy controls matched for age and gender participated in this cross-sectional study. To evaluate arterial blood gas pressure, arterial blood was obtained from the radial artery. Pressure pain threshold was assessed over paraspinal muscles between C7-T7 using a pressure algometer. Psychological characteristics were obtained with self-administered questionnaire using Hospital Anxiety and Depression rating Scale, Perceived Stress Scale -10 and Pain Catastrophizing Scale. Carbon dioxide, oxygen, bicarbonate, base excess, pH and lactate were analysed for in-between group differences. Statistical analyses included descriptive statistics and the student’s t-test was used to compare differences between groups. Linear regression was used to adjust for possible confounders on blood gas variables.

Results: Women with FM had significantly lower carbon dioxide pressure (p=0.013) and higher lactate (p=0.038) compared to healthy controls and were still significant when adjusted for smoking, BMI and age (p<0.05). There were no significant differences in oxygen pressure, bicarbonate, base excess or pH. There were no correlations between pressure pain threshold, psychological characteristics and blood gas variables. 47% in the FM group and 27% in the control group were below the reference for normocapnia (4.7–6.0 kPa).

Conclusion: In our study, women with FM had significantly lower arterial carbon dioxide pressure and higher lactate compared to healthy controls. The results might point to a plausible dysfunctional breathing in some women with FM.

Combined Intervention of Painful Diabetic Neuropathy with Medication, Hypnosis and Cognitive Behavioural Therapy: A Randomised Control Trial (#58)

Adzika, Vincent, Pedro, Athena

University of the Western Cape, Bellville, Cape Town, South Africa

Clinical Research

Background: The chronic pain associated with painful diabetic neuropathy (PDN) is considered painful crises that involve psychological complications in addition to the sensations. A repeated attempt to solve the problem of PDN from a biomedical perspective has resulted in a cycle of low health quality of life, sleep disturbance, depression, anxiety and pain catastrophizing. An effective treatment of PDN would require pharmacotherapies-treatment as usual (TAU) supplemented by non-pharmacological approaches like cognitive behavioral therapy (CBT) and hypnosis (HYP).

Aim: This study evaluated the efficacy of the combined intervention of painful diabetic neuropathy with medication, hypnosis and cognitive behavioral therapy in a randomized control trial in a clinic setting.

Method: The study employed an experimental approach for interventions, collecting and analyzing data of 125 respondents sampled from a diabetes clinic. It applied a TAU plus CBT and HYP randomized with TAU plus CBT in the intervention of PDN patients. Data was collected with the Leeds Assessment of Neuropathic Symptoms and Signs Scale, and the Brief Pain Inventory for Painful Diabetic Peripheral Neuropathy. The data was analyzed with Pearson’s Correlation coefficient, Chi-squared Test of Association, Student’s t-test and Analysis of Variance (ANOVA).

Results: The study affirmed that after the introduction of hypnosis (HYP) to the experimental group, there was a statistically significant reduction in pain intensity and interference in the experimental group (TAU + CBT + HYP) compared with the control group (TAU + CBT).

Conclusion: This study, therefore, concludes that there was a significant improvement after the combined intervention of medication, CBT and HYP for PDN.

Development of credible explanations: Exploring key domains to tailor explanations to adolescents with non-traumatic knee pain (#61)

Djurtoft, Chris¹ Bruun, Malene Kjær¹, Riel, Henrik¹, Høgh, Morten Sebastian¹, Darlow, Ben², Rathleff, Michael Skovdal¹

¹Aalborg University, Aalborg, Denmark

²University of Otago, Wellington, New Zealand

Clinical Research

Aims: Diagnostic uncertainty leaves patients confused and impede their ability to understand “what’s wrong with me”. Perceived diagnostic uncertainty is associated with higher anxiety and lower acceptance of self-management recommendations, highlighting the need to improve explanations and reduce uncertainty. This study aimed to explore key domains to include when tailoring credible explanations to adolescents experiencing non-traumatic knee pain.

Method: This mixed-method study integrated findings from a systematic search of qualitative studies in Medline and an Argumentative Delphi with international experts (n=19). We screened 3239 titles/abstracts and included 16 papers which explored the complex experience of diagnostic uncertainty from adolescents’ perspective. These findings were used to develop the first version of a credible explanation. Subsequently, experts provided feedback with arguments on how to tailor and communicate explanations to meet adolescent needs. We analysed all feedback using thematic analysis before integrating findings.

Results: The systematic search revealed five themes: (1) Label: Having a name for pain; (2) Validation and reassurance: Feeling stigmatized for having an invisible condition; (3) Etiology and cause of pain: Understanding causes and contributors to pain experience; (4) Not something else: Need for explanations that rule out other diagnoses; (5) Controllability: Value information regarding controllability of pain. The Delphi revealed the following themes: Tailored to adolescents, Careful wording, Validation and reassurance, and Multidimensional perspective. After integrating findings from the systematic search and the Delphi, three essential domains to address in a credible explanation emerged: “What is non-traumatic knee pain and what does it mean?”, “What is causing my knee pain” and “How do I manage my knee pain?”.

Conclusion: Our results provided three essential domains for clinicians to consider when tailoring explanations to adolescents experiencing non-traumatic knee pain. A credible explanation about why adolescents experience non-traumatic knee pain is a cornerstone of management and may reduce perceived diagnostic uncertainty.

Development of credible explanations for individuals experiencing musculoskeletal pain using adolescent non-traumatic knee pain as a model: An iterative development process (#62)

Bruun, Malene Kjær¹ Djurtoft, Chris¹, Riel, Henrik¹, Høgh, Morten¹, Darlow, Ben², Rathleff, Michael Skovdal¹

¹Aalborg University, Aalborg, Denmark

²University of Otago, Wellington, New Zealand

Clinical Research

Aims: Better communication about non-specific pain conditions was recently voted as one of the top research priorities in the musculoskeletal pain field. Despite the need for better communication there is limited research addressing how to develop credible explanations that meet user needs. The aim of this study was to develop and implement a framework to systematically tailor credible explanations for painful musculoskeletal conditions

Method: We developed a five-stage framework which included an iterative process. The five stages of the framework were: 1) Review of the literature 2) Product development; 3) Argumentative Delphi; 4) Consensus; 5) End-user testing. In stage 1, two systematic searches were performed: one about etiology and one including qualitative studies exploring adolescents’ perspectives. In stage 2, the first drafts of the explanations were produced using an iterative process within the research group, guided by the literature searches. In stage 3, an Argumentative Delphi with international experts was conducted through REDCap and content was iteratively revised after analysing all feedback using thematic analysis. Stage 4 included a revision by the research group through consensus. In stage 5 (not yet completed) the explanations will be tested on at least 15 end-users which will lead to final revisions and ends the iterative process.

Results: This five-stage framework has supported the application of evidence-based medicine systematically by integrating best research evidence, clinical expertise, and patient perspectives. As a result, credible explanations were developed for six common non-traumatic knee conditions. These explanations contain three essential domains for explaining adolescents non-traumatic knee pain to adolescents and will be tested with end-users.

Conclusion: Through our five-stage framework, we have developed credible explanations that aligns with evidence, clinical expertise, and patient perspectives. This study extends current practice by providing a framework for systematically developing credible explanations which may be used for other painful musculoskeletal conditions.

Acute and Chronic Neuropathic Pain after Spinal Cord Injury (#68)

Rosner, Jan¹ Finnerup, Nanna², Kwon, Brian³, Kramer, John L.K.³

¹University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland, Bern, Switzerland

²Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, Aarhus, Denmark

³University of British Columbia, Vancouver, British Columbia, Canada, Vancouver, Canada

Clinical Research

Aims: Acute neuropathic pain poses a significant diagnostic challenge, especially in the case of traumatic spinal cord injury (SCI) as nociceptive and neuropathic pain are often concurrently present. Consequently, there is a lack of clinical information regarding the phenotype of neuropathic pain present within the early stages of SCI.

The aim of this study was to characterize the phenotype of neuropathic pain present in the acute phase of SCI. Moreover, the phenotype of acute neuropathic pain was compared to that observed at chronic timepoints.

Method: Information pertaining to neuropathic pain after SCI was prospectively collected in a longitudinal multicenter study (CAMPER trial, ClinicalTrials.gov, NCT01279811). Illustrative case examples (n=3) were gathered at a major trauma center in Switzerland (Bern University Hospital). In addition to a thorough clinical examination according to the International Standards for Neurological Classification of Spinal Cord Injury, pain assessments were performed following state-of-the-art recommendations. The DN4-questionnaire was used to characterize pain related symptoms.

Results: Within the hyperacute time-frame (i.e., 5 days post injury) at- and below level pain were reported in 23% (n=18) and 5% (n=4) of individuals with acute SCI, respectively. The symptoms between hyperacute and late presenting neuropathic pain differed with regard to the intensity painful electrical sensations, cold sensations and itching. The examination in the acute phase was often limited in the setting of the intensive care unit.

Conclusion: The assessment of acute neuropathic pain is restricted in the acute setting and needs to be focused and directed towards anatomically plausible regions, i.e., within the affected segments and outside of areas with concomitant musculoskeletal damage. Consensus guidelines are needed outlining adapted diagnostic criteria and recommendations regarding the longitudinal tracking of neuropathic pain. Such tracking should incorporate the spatial distribution of pain and neurological outcomes.

Transcriptome-wide profiling of microRNAs and circular RNAs in patients with chronic postsurgical neuropathic pain (#73)

Palada, Vinko

Kalso, Eija

University of Helsinki, Helsinki, Finland

Clinical Research

Aims: Chronic postsurgical neuropathic pain (CPSNP) is a leading cause of neuropathic pain (NP), triggered by the primary lesion of the peripheral nerve during the surgery. Molecular mechanisms associated with development of CPSNP after surgery are poorly understood and it is unknown why only a subset of surgical patients develop CPSNP after the same type of nerve injury.

Methods: In the current study, we performed a transcriptome-wide profiling of two classes of non-coding RNAs (ncRNAs), miRNAs and circular RNAs (circRNAs), in clinically well-defined cohort of postsurgical breast cancer patients with surgeon-verified injury of intercostobrachial nerve and compared the expression of ncRNAs in subsets of patients with and without CPSNP to identify the novel biomarkers for CPSNP. We also examined the causal relationship between differentially expressed miRNAs and circRNAs to investigate the potential regulatory pathways and have accessed the correlation of ncRNA expression with clinical symptoms.

Results: As a result, we identified 57 differentially expressed miRNAs in plasma and 3 circRNAs with altered expression in blood based on the presence or absence of CPSNP. Our findings support the existence of regulatory circRNA-miRNA-mRNA networks which might contribute to NP either directly by modulating pain or indirectly by regulating pain comorbid conditions and inflammation.

Conclusion: Altered expression of miRNAs and circRNAs in plasma and blood from CPSNP patients supports their potential as diagnostic biomarkers while the predicted interactions between circRNAs and miRNA/mRNA targets might be utilized to develop novel therapeutics for NP.

A survey study on cancer related pain in Swedish adults - patients with cancer related chronic pain report low access to psychological treatment (#16)

Björkstrand, Frida¹ Duarte, Joana¹, McCracken, Lance², Perrin, Sean³

¹Lund University, Lund, Sweden

²Uppsala University, Uppsala, Sweden

³Lund University, Lund, Sweden

Observational study

Aims: Cancer is a common and debilitating disease, with an estimated 18 million new cases each year. Among the burdens experienced by cancer patients, pain is one of the most common. Furthermore, cancer is one of the most common reasons for pain in the general population. Chronic pain can be effectively treated with psychological therapy. Although not evaluated specifically for cancer related pain, these interventions could be of benefit to cancer patients. However, whether psychological treatments are offered to patients with cancer pain in Swedish adults is not known.

Methods: We conducted an online survey, targeting Swedish adults with previous or current cancer diagnosis. We reached a sample size of 276 individuals. The survey included questions about demographic variables, cancer history, previous and ongoing chronic pain problems, and access to treatment for pain (pharmacological and psychological).

Results: The collected sample was primarily female (83%), upper middle age (M=55,5; SD=11,9), and reported a cancer history mainly consisting of breast (36%), gynecological (12%), lung (10%) and colon cancer (8%). A majority of the sample (74%) reported having experienced chronic pain, out of which 74% reported ongoing pain problems. Out of those reporting chronic pain, 14% had been offered or referred to psychological pain treatment, whereas 60% of the total sample had been prescribed medication for cancer related pain.

Conclusions: In this observational study we find that chronic pain is common in Swedish cancer patients, but they are rarely offered psychological treatment. Psychological interventions are generally the preferred treatment for chronic pain problems, but cancer patients with chronic pain appear to have low access to these services. Developing psychological treatments, meeting the needs of patients with cancer-related pain, is called for, as well as working to make these treatments accessible for patients with cancer-related pain.

Quality of life and work ability in workers with pain - an observational study (#21)

Zakrzewski, Filip Mariusz¹ Johansen, Frida E. Engelbrecht², Andersen, Erika Maria²

¹Aalborg University, Valby, Denmark

²Aalborg University, Aalborg, Denmark

Observational study

Aim: Health-related quality of life and work ability are relevant concepts for all workers. The aim of this study was to examine the differences between health-related quality of life and workability among workers with or without pain and investigate associations between the two concepts and pain self-efficacy. Health-related quality of life was collected with the European Quality of Life five dimensional-5L (EQ-5D-5L), and workability with the Work Ability Index (WAI) as primary measurements. Pain Self-efficacy 4 (PSEQ-4) and Numeric Rating Scale (NRS) as secondary measurements.

Method: Data was collected from 688 Danish workers between February and March using an online survey. Blue-collar (n=239) and white-collar (n=449), men (51%) and women (49%) (aged 18–65+). Respondents were divided into two groups: mild pain and moderate-severe pain. Mann Whitney U test was used to assess the differences between respondents with mild and moderate-severe pain. To investigate the association between the primary and secondary outcomes, a Spearman’s rho test was conducted.

Results: Respondents with mild pain had better quality of life and work ability compared to respondents with higher pain intensity. There was a significant association between all three outcome measures (EQ-5D-5L, WAI and PSEQ-4). Results showed a stronger association between the quality of life, workability and pain self-efficacy for respondents with moderate-severe pain compared to respondents with mild pain.

Conclusion: Workers with mild pain and pain free workers appear to report equal quality of life and workability, whereas workers with moderate-severe pain report lower health-related quality of life and work ability than the aforementioned groups. This indicates that workers with mild pain are less affected in quality of life as well as work ability and are more likely to stay at work compared to workers with moderate-severe pain.

Engaging stakeholders within chronic musculoskeletal pain to direct future research for improving the lives of people living in pain (#24)

Lyng, Kristian Damgaard¹ Larsen, Jesper Bie¹, Birnie, Kathryn², Stinson, Jennifer², Hoegh, Morten¹, Olesen, Anne Estrup¹, Arendt-Nielsen, Lars¹, Ehlers, Lars³, Fonager, Kristen⁴, Jensen, Martin Bach¹, Würtzen, Hanne⁵, Palsson, Thorvaldur¹, Poulin, Patricia⁶, Handberg, Gitte⁷, Ziegler, Connie⁸, Moeller, Lars⁹, Olsen, Judi¹⁰, Heise, Lotte¹¹, Rathleff, Michael Skovdal¹

¹Aalborg University, Klarup, Denmark

²Canada

³Nordic Institute of Health Economics (NIHE), Aalborg Øst, Denmark

⁴Aalborg University Hospital, Aalborg, Denmark

⁵Rigshospitalet, Copenhagen, Denmark

⁶Department of Psychology, The Ottawa Hospital, Ottawa, Canada

⁷Pain Center, Odense University Hospital, Odense, Denmark, Odense, Denmark

⁸Gigtforeningen, Copenhagen, Denmark

⁹FAKS, Copenhagen, Denmark

¹⁰Fibromyalgi.dk, Copenhagen, Denmark

¹¹Danish Broadcast Cooperation, Copenhagen, Denmark

Observational study

Background: Engaging key stakeholders in research has exponentially increased and the value has been highlighted multiple times. People living with chronic musculoskeletal pain (PwCMP) and other relevant stakeholders (including relatives and clinicians) need to be involved in the idea generation of new research to ensure clinical relevancy for future studies. We initiated a priority-setting partnership (PSP) study to engage PwCMP and other stakeholders to establish the priorities for future research.

Method: Over 1100 stakeholders participated in this PSP study. The participants participated through three different phases including a survey for collecting research questions, an interim prioritisation exercise and a workshop to establish the top priorities.

Results: Over 3000 potential research questions were submitted for review by the author group. From these 55 unique research questions were formulated and further reduced to 33 questions based on the prioritisation exercise. Of these, a top-10 list was created based on a workshop with stakeholders representing both PwCMP, relatives and clinicians.

Conclusion: Based on this study, future research should, among others, prioritise improving specialised care for PwCMP, improving diagnostic accuracy, determining the most effective treatment, improve the general understanding of chronic musculoskeletal pain in both PwCMP, and clinicians and the public. The results from this study can help direct future research and inform policymakers on where to invest resources.

Gray matter volume and pain tolerance in a general population: The Tromsø Study (#59)

Melum, Tonje Anita¹ Vangberg, Torgil², Johnsen, Liv-Hege³, Steingrímsdóttir, Ólöf Anna⁴, Stubhaug, Audun⁵, Mathiesen, Ellisiv⁶, Nielsen, Christopher⁷

¹University Hospital of Northern Norway/UiT the Arctic University of Norway, Tromsø, Norway

²Tromsø PET Imaging Center, University Hospital of Northern Norway, Tromsø, Norway

³Department of Radiology, University Hospital of Northern Norway, Tromsø, Norway

⁴Department of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway

⁵Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway

⁶Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic Univ, Tromsø, Norway

⁷Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway

Observational study

Aims: Pain is processed by an extensive network of brain regions, suggesting that the structural status of the brain may affect pain perception. Studies of the association between gray matter and pain sensitivity are generally small and findings inconsistent. We aimed to study this association in a general population, using cold pressor pain tolerance time as a measure of pain sensitivity.

Method: Analysis was performed on 1522 men and women from the 7th wave of the Tromsø study, who had completed the cold pressor test (3°C, maximum time 120s) and undergone MRI of the brain, and for whom information on covariates where available. Cox proportional hazards regression models were fitted with time to hand withdrawal from cold exposure as outcome. Gray matter volume, standardized by z-transformation, was the independent variable and analyses were adjusted for intracranial volume, age, sex, education level and cardiovascular risk factors. Additional adjustment was made for chronic pain and depression in subsamples with available information on the respective item. Post-hoc analyses were performed on gray matter volume in individual brain regions.

Results: Standardized total gray matter volume was associated with risk of hand withdrawal from cold exposure (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.71 to 0.93), indicating that larger gray matter volume is associated with increased pain tolerance. The effect remained significant after additional adjustment for chronic pain (HR 0.84, 95% CI 0.72–0.97) or depression (HR0.82, 95% CI 0.71–0.94). In post-hoc analyses, positive associations between standardized gray matter volume and pain tolerance were seen in most brain regions, with larger effect sizes in regions previously shown to be associated with pain.

Conclusion: Gray matter volume is positively associated with pain tolerance in the general population.

Cancer-related neuropathic pain (CRNP) in Europe: burden of CRNP and the impact of diagnosis on treatment of patients* (#63)

Bell, Dany¹ Brill, Silviu², Barragán, Begoña³, Dupoiron, Denis⁴, Eeltink, Corien⁵, Petersen, Gudula⁶, Eerdekens, Marielle⁶, Ryan, Deidre⁷, Rakusa, Martin⁸

¹Macmillan Cancer Support United Kingdom, London, United Kingdom

²Institute for Pain Medicine, Tel Aviv Medical Center, Israel, Tel Aviv, Israel

³Grupo Español de Pacientes con Cáncer (GEPAC), Madrid, Spain

⁴Institut de Cancérologie de l’ouest Département Anesthésie, Angers, France

⁵Amsterdam UMC, location VUmc, department of Hematology, Amsterdam, Netherlands

⁶Grünenthal, Aachen, Germany

⁷Pain Alliance Europe, Diegem, Machelen, Belgium

⁸Department of Neurology University Medical Centre, Maribor, Slovenia

Observational study

Aims: CRNP is common but difficult to diagnose/treat in clinical practice. A European patient survey was conducted assessing the impact of CRNP on patients and whether there are any differences in pain support across the cancer journey.

Method: An online survey, prepared, conducted and analysed with an expert-team including physicians, nurses and patients, was completed in June 2021. Adults consenting to participate and diagnosed with cancer were screened for symptoms of neuropathic pain. Respondents meeting minimally three DN4 criteria were enrolled and answered questions about their experiences regarding the burden, diagnosis and management of CRNP.

Results: 549 persons living with CRNP were recruited across 13 European countries incl. Denmark (n=43/7,8%), Norway (n=28/5,1%), Sweden (n=49/8,9%). 88% were ≤ 65 y/o and 89% fulfilled ≥4 DN4 criteria. Most CRNP patients experienced severe (32%) or moderate (44%) pain on a daily basis. CRNP had an impact on sleep patterns, mental health and ability to exercise; 30% had to retire/stop working (SE: 41%; DK: 30%; NO: 39%). Whilst 59% were satisfied with the recommended CRNP treatments/interventions, 26% reported that nothing was done after discussing CRNP with their physician. < 50% respondents expectation was to keep the pain at a bearable level. 86% of respondents had little knowledge around CRNP across Europe (SE: 92%; DK: 88%; NO: 93%). Despite CRNP symptoms, 40% had not received a formal diagnosis of neuropathic pain. Those with CRNP diagnosis were more likely to get pharmaceutical treatment (67% vs 44%) or physiotherapy (35% vs 22%) and were more likely to be satisfied with their treatment (67% vs 43%).

Conclusion: CRNP negatively impacts the daily life of patients; diagnosis of CRNP remains a challenge and many of those affected seem to remain unrecognised. Those without diagnosis are less likely to be treated for pain.

*Grünenthal has financially supported this survey.

Cancer-related neuropathic pain (CRNP) in europe: impact of cancer stage on diagnosis and treatment of patients* (#65)

Bell, Dany¹ Brill, Silviu², Barragán, Begoña³, Dupoiron, Denis⁴, Eeltink, Corien⁵, Eerdekens, Marielle⁶, Petersen, Gudula⁶, Ryan, Deidre⁷, Rakusa, Martin⁸

¹Macmillan Cancer Support United Kingdom, London, United Kingdom

²Institute for Pain Medicine, Tel Aviv Medical Center, Israel, Tel Aviv, Israel

³Grupo Español de Pacientes con Cáncer (GEPAC), Madrid, Spain

⁴Institut de Cancérologie de l’ouest Département Anesthésie , Angers, France

⁵Amsterdam UMC, location VUmc, department of Hematology, Amsterdam, Netherlands

⁶Grünenthal, Aachen, Germany

⁷Pain Alliance Europe, Diegem, Machelen, Belgium

⁸Department of Neurology University Medical Centre, Maribor, Slovenia

Observational study

Aims: CRNP is common but difficult to diagnose/treat in clinical practice. A European patient survey was conducted assessing the impact of CRNP on patients and whether there are any differences in pain support across the cancer journey.

Method: An online survey, prepared, conducted and analysed with an expert-team including physicians, nurses and patients, was completed in June 2021. Adults consenting to participate and diagnosed with cancer were screened for symptoms of neuropathic pain. Respondents meeting minimally three DN4 criteria were enrolled and answered questions about their experiences regarding the diagnosis and management of CRNP.

Results: 549 persons from 13 European countries participated in the study incl. Denmark (n=43/7,8%), Norway (n=28/5,1%), Sweden (n=49 /8,9%); recruiting 88% ≤ 65 y/o. 32% experienced severe pain daily, 89% had signs and symptoms consistent with CRNP. In the presence of CRNP symptoms, 40% had no HCP confirmed diagnosis of neuropathic pain. The respondents were either in active cancer treatment (n=240/44%), no active cancer treatment but still in oncology care (n=232/42%), were no longer in oncology care (i.e. a ‘cancer survivor’) (n=70/13%), or not yet in cancer-treatment (n=7/1%). Compared to those currently in active cancer treatment, cancer survivors were less likely to have a diagnosis of CRNP (69% vs 53%) or regular conversations with HCPs about their pain, received fewer pain treatments, and described feeling less support and empathy from HCPs around their pain. Correspondingly a higher proportion of participants in Sweden were still in active treatment or contact with oncologist, had received a formal diagnosis and were overall satisfied with their treatment compared to DK/NO.

Conclusion: Even though CRNP has a substantial impact on patients’ lives, it remains under-recognised and especially in cancer survivors who are no longer in active cancer care, special focus on pain management is needed.

*Grünenthal has financially supported this survey.

Health-Related Quality of Life, lifestyle and pain: The first step in a longitudinal national study (#77)

Jonsdottir, Thorbjorg

University of Akureyri, Akureyri, Iceland

Observational study

Aims: The project involves building an extensive database on pain, health-related quality of life (HRQoL), lifestyle, and life-experiences. The aim is to investigate complexed relationships between pain and diverse lifestyle and life-experiences.

Method: This is a cross-sectional study, but at the same time the beginning of a longitudinal project where participants will be contacted again after 5 and 10 years. Data was collected through a web-based platform where 12.400 individuals aged 18–80 years were invited to participate. Information was collected on pain (e.g. nature, spread and pattern), HRQoL and several aspects regarding people’s general lifestyles, e.g., employment, use of tobacco, alcohol, and other intoxicants, sleep and body mass index (BMI) as well as information on experiences of chronic illnesses and trauma such as accidents and violence. Participants were also asked about access to and use of health services.

Results: Answering rate was 45% (N=5.557). Half of the participants (50,3%) had experienced pain last week and 40% had chronic pain (≥ 3 months). Of those reporting chronic pain 65% had constant or daily pain and 35% frequent or periodic pain. Most common causes of pain were ‚wear and tear‘, osteoarthritis and earlier injuries and most common pain locations were shoulders (46%), low-back (40%) and knee (43%). There was a statistically significant correlation found between chronic pain and several life-style variables such as smoking, sleep, and BMI as well as life-experiences such as history of physical or psychological trauma related to accidents or violence. Vast majority of participants (81%) accepted to be contacted again for further participation.

Conclusion: There is a complexed relationship between chronic pain and people’s lifestyle and life-experiences. These relationships need to be investigated over time and this longitudinal study will provide information on long term development between these variables.

Somatosensory outcomes following re-surgery in persistent severe pain after groin hernia repair: a prospective observational study (#28)

Kjær Jensen, Elisabeth¹ Ringsted, Thomas K.¹, Bischoff, Joakim M.¹, Petersen, Morten A.², Møller, Kirsten¹, Kehlet, Henrik¹, Werner, Mads U.¹

¹Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark

²Bispebjerg Hospital, Copenhagen, Denmark

Observational study

Aims: Groin hernia repair is accompanied by persistent severe pain in 2–4% of the patients, significantly restraining psychophysical functions. Re-surgery with meshectomy and selective neurectomy may improve the pain condition compared to non-surgical alternatives. In the current study, the primary objective was to examine and describe the underlying pathophysiological perturbations by quantitative somatosensory testing before and after re-surgery.

Methods: Sixty patients with persistent severe pain after groin hernia repair were examined in median (95% CI) 7.9 (5.8–11.5) months before and 4.0 (3.5–4.6) months after re-surgery. The quantitative somatosensory testing included standardized assessments of cutaneous mechanical/thermal detection and pain thresholds. Suprathreshold heat stimuli were applied. Deep tissue sensitivity was tested by pressure algometry. Testing sites were the groins and the lower arm. Before/after quantitative somatosensory test data were z-transformed. Multivariate multiple regression analyses examined the associations between the somatosensory testing and the clinical outcomes, i.e., pain intensity scores and physical functions.

Results: Compared with the control sites, the cutaneous somatosensory detection thresholds of the painful groin were increased already before re-surgery and increased further after re-surgery, indicating a successive post-surgical loss of nerve fiber function (‘deafferentation’). Pressure algometry thresholds increased after re-surgery indicating a decrease in the deep tissue sensitivity. No meaningful regression model could be inferred from the somatosensory testing data and the clinical outcomes.

Conclusions: While the increase in somatosensory detection thresholds mirrors the surgery-induced cutaneous deafferentation, the increase in pressure algometry thresholds mirrors the removal of the deep ‘pain generator’ by the re-surgery, including meshectomy and selective neurectomy. The somatosensory analyses in a cogent way present the dynamic pathophysiology after the primary groin hernia repair as well as after the secondary re-surgery. The analyses seem useful adjuncts in mechanism-based somatosensory research.

Association of Inflammatory Plasma Proteins, Muscle Blood Flow and Metabolism with Body Mass Index and Pain Characteristics in Women with Fibromyalgia (#38)

Ghafouri, Bijar¹ Edman, Emelie¹, Löf, Marie², Lund, Eva¹, Dahlqvist Leinhard , Olof¹, Lundberg, Peter¹, Forsgren, Mikael¹, Gerdle, Björn¹, Dong, Huan-Ji¹

¹Linköping University, Linköping, Sweden

²Karolinska Institutet, Huddinge, Sweden

Original Experimental study

Aim: This study aimed to investigate if the inflammatory plasma protein profile, muscle blood flow and metabolism and pain characteristics (clinical parameters and patient reported outcome measurements) differed between FM patients with and without obesity.

Methods: FM patients (n=27) underwent clinical examinations, physical tests and answered questionnaires. They were dichotomized according to BMI (<30 kg/m² (n = 14), ≥30 kg/m² (n = 13)). Blood samples were collected and analyzed using a panel of 71 cytokines and chemokines (Meso Scale Discovery, Maryland, USA).

Results: The obese group showed significant (p<0.05) higher blood pressure, pulse, pain intensity, and Fibromyalgia Impact Questionnaire (FIQ) and lower physical capacity and max VO2 compared to non-obese group. A significant OPLS-DA model could discriminate obese FM from non-obese based on 14 proteins. The four most important proteins for the group belonging were MIP1β, MCP4, IL1RA and, IL6 which showed higher concentrations in obese FM patients. Significantly decreased blood flow and increased concentration of pyruvate were detected in obese patients compared to non-obese. There was significant correlation between inflammatory proteins and sedentary behavior and health status, in obese FM.

Conclusions: These findings suggest that metabolism and inflammation are interacting in FM with obesity that can lead to chronic low-grade inflammation.

P2Y14 receptor in trigeminal ganglion contributes to orofacial inflammatory pain (#41)

Lin, Jiu¹ Fang, Xinyi², Shen, Jiefei¹

¹West China Hospital of Stomatology, Sichuan University, Chengdu, China

²School of Stomatology, Zhejiang University School of Medicine, Hangzhou, China

Original Experimental study

Aims: Orofacial inflammatory pain is a common complication in various dental and oral procedures. Recently, P2 purinergic receptors have emerged as novel targets against such pain. However, the role and mechanism of P2Y₁₄ receptor (P2Y₁₄R) in orofacial inflammatory pain remain unknown.

Methods: Orofacial inflammatory pain was induced by injection of complete Freund’s adjuvant (CFA) into the whisker pad area. Orofacial mechanical threshold was measured by Von-Frey tests. The location of P2Y₁₄R was detected by immunofluorescence in the trigeminal ganglion (TG). The P2Y₁₄R antagonist (PPTN) was delivered by trigeminal ganglion injection before CFA treatment. Cultured satellite glial cells (SGCs) were treated with P2Y₁₄R agonist (UDP-glucose) combined with PPTN, extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor (U0126), or p38 inhibitor (SB203580). Both in vivo and vitro, the expression of P2Y₁₄R and its potential downstream cellular signaling was measured by RT-qPCR, western blot (WB), and/or ELISA.

Results: Firstly, CFA induced orofacial mechanical hypersensitivity. The increased glial fibrillary acidic protein (GFAP) expression in TG implied SGCs activation. P2Y₁₄R was expressed in trigeminal ganglion neurons and SGCs. CFA increased the expression of P2Y₁₄R, GFAP, interleukin-1β (IL-1β), and C-C chemokine CCL2 in TG. Secondly, PPTN alleviated CFA-induced mechanical hypersensitivity, SGCs activation, and above cytokines production in TG. In vitro, UDP-glucose activated SGCs and increased IL-1β and CCL2 secretion, which were also reduced by PPTN. Thirdly, phosphorylated ERK1/2 and p38 were upregulated in TG of the CFA model and UDP-glucose-treated SGCs, which were decreased by PPTN. Furthermore, the inhibitors of ERK1/2 (U0126) and p38 (SB203580) reduced these UDP-glucose-induced IL-1β and CCL2 in SGCs.

Conclusions: The present study demonstrated that P2Y₁₄R in TG may contribute to orofacial inflammatory pain via regulating SGCs activation, releasing cytokines (IL-1β and CCL2), and phosphorylating ERK1/2 and p38.

Paradoxical Heat Sensations are influenced by both baseline temperature and individual thermal thresholds (#50)

Mitchell, Alexandra¹ Sardeto Deolindo, Camila¹, Sandberg, Kristian¹, Fardo, Francesca¹

¹Aarhus University, Aarhus, Denmark

Original Experimental study

Aim: Paradoxical Heat Sensations (PHS) are an illusory experience of heat that occur during the cooling phase of the Thermal Sensory Limen (TSL) task. Our limited understanding of PHS is, in part, due to poorly controlled procedures. The aim of this study was to further our understanding of PHS by using a modified version of the TSL (mTSL, Schaldemose et al., in press) to explore the relationship between PHS, thermal thresholds and pre-warming during TSL.

Method: A large sample (n=208) of healthy adults completed a mTSL task, where both the baseline and pre-warming temperatures (32, 38 or 44°C) were controlled. Stimuli were delivered on the internal surface of either forearm. After an auditory tone, indicating when the probe reached 32°C, participants reported when they experienced any change in sensation quality (innocuous condition) or a painful sensation (noxious condition) during the cooling phase. Variables of interest were the participant’s qualitative response (i.e. veridical sensation vs paradoxical heat sensation) and the associated thermal threshold (i.e. temperature change threshold and pain threshold) for each pre-warming temperature at the single trial level.

Results: The frequency of innocuous PHS, feeling warmth or heat during the cooling phase, increased with higher pre-warming temperatures (McNemar’s test: 32 vs. 38° p = 0.038; 38 vs 44° p = 0.002), but not noxious PHS (32 vs. 38° p = 0.038; 38 vs 44° p = 0.002). A logistic regression also revealed that the probability of PHS significantly increased with lower cold detection (OR = .01, p < 0.001) and higher pain thresholds (OR = 1.40, p < 0.001).

Discussion: This study suggests that the underlying PHS mechanisms are mediated by both baseline temperature and individual thermal and pain thresholds. Our results also highlight how carefully controlled administration of the TSL in neurotypical adults can improve our understanding of PHS.

A Multi-Dimensional Adaptive Psychophysical Approach to Estimating the Thermal Grill Illusion (#60)

Sardeto Deolindo, Camila¹, Ehmsen, Jesper Fischer¹, Mitchell, Alexandra Grace¹, Andersen, Camilla Eva¹, Nikolova, Niia¹, Allen, Micah Gallen^1,2, Fardo, Francesca¹

¹Aarhus University, Aarhus, Denmark

²University of Cambridge, England

Original Experimental study

Aims: Alternating innocuous cold and warm stimuli on the skin can produce an illusory sensation of strong heat and pain, known as the thermal grill illusion (TGI), exhibited by 60% of the healthy population. However, currently there is no systematic method for choosing the stimulus temperatures, which may bias investigations. Thus, we propose a new psychophysical approach to identify subjective TGI thresholds.

Method: We developed an adaptive thresholding method that characterizes a Thermal grill Psychometric Function (TGPF) within a two-dimensional stimulus manifold, corresponding to the combined cold and warm temperatures at which a burning sensation is reliably elicited. TGPFs were fitted for 6 healthy participants in 100 adaptive trials each. We then evaluated the fit of the function by asking participants to rate the felt cold, warmth, and burning intensity of above, below, and peri-threshold stimuli.

Results: Our results demonstrate that it is possible to identify several combinations of innocuous cold and warm temperatures that consistently elicit TGI phenomenon. In particular, there was a significant decrease in burning ratings when cold and warm temperatures were individually presented (Linear Mixed Effect Model - LME: TGI vs warm z=-3.7 p <0.0005, TGI vs cold z = -5.1 p < 0.0001). Crucially, TGI burning ratings were further increased when moving from below to near and above threshold stimulus combinations (LME: threshold vs below z=-2.8 p <0.005, threshold vs above z = -6.2 p < 0.0001).

Conclusion: Our results highlight the efficacy of our method to estimate and control the intensity of burning sensations of the TGI. Our method is both efficient and robust, requiring only 100 trials and enabling experimental delivery of peri-threshold illusory pain stimuli. This advance opens new avenues for thermal pain research, including the ability to test different experimental groups and conditions on sensitivity to equated TGI stimuli.

Relationship between selective small fiber activation and corneal confocal microscopy in type 1 diabetes (#67)

Røikjer, Johan, Mørch, Carsten Dahl

Croosu, Suganthiya Santhiapi, Hansen, Tine Maria, Frøkjær, Jens Brøndum, Ejskjaer, Niels

Aalborg University, Aalborg, Denmark

Original Experimental study

Aim: Early detection of diabetic peripheral neuropathy (DPN) is pivotal in delaying or preventing diabetic foot ulcer development. Assessment of small fiber neuropathy has proven more difficult, leaving structural measures of the intraepidermal nerve fiber density, and corneal confocal microscopy (CCM) as the golden standards for small fiber assessment. These measures are rarely performed in daily clinical practice. The aim of the present study was to assess the diagnostic performance of perception threshold to selective electrical small fiber stimulation for detection of small fiber neuropathy (SFN) with corneal nerve fiber integrity as reference.

Methods: A total of 60 participants with type 1 diabetes (T1DM) and 20 healthy controls (HC) were included in an initial cohort (MEDON: NCT04078516). Nine participants were subsequently excluded due to previous bilateral refractive surgery; thus the 71 participants were included in the analysis. As part of the assessment of small fiber excitability using perception threshold tracking, the perception threshold to a 1ms rectangular pulse was assessed. The small cutaneous nerve fibers were selectively activated with a small cathode array electrode. The participants also underwent corneal confocal microscopy (CCM) following usual guidelines. Corneal nerve fiber integrity was analyzed as corneal nerve fiber length (CNFL). Diagnostic agreements were achieved utilizing logistic regression with the lower 5% percentile of the CNFL in the HC group as the indicator of SFN.

Results: Categorizing the participants into persons with or without SFN had an optimal cut-off intensity of 334 µA. This resulted in a sensitivity of 82%, a specificity of 81%, positive predictive value of 80%, a negative predictive value of 84%, and an accuracy of 90%.

Conclusion: The perception threshold of small fiber specific electrical activation had high diagnostic performance and may therefore be considered when screening for SFN.

Uncertainty modulates veridical temperature perception and illusory pain in a volatile learning environment (#69)

Fischer Ehmsen, Jesper¹ Deoli, Camila Sardeto², Andersen, Camilla Eva², Christensen, Daniel Elmstrøm², Mathys, Christoph³, Allen, Micah², Fardo, Francesca²

¹Aarhus University, Aarhus, Denmark

²Center of Functionally Integrative Neuroscience, Aarhus University, Denmark, Aarhus, Denmark

³School of Culture and Society - Interacting Minds Centre, Aarhus, Denmark

Original Experimental study

Aims: Expectations influence how strongly we feel pain. However, little is known about the mechanisms that integrate sensory signals with expectations in “illusory” pain phenomena such as the thermal grill illusion (TGI). We investigated how expectations of variable uncertainty shape both veridical and illusory thermal sensations, using a novel thermal learning paradigm. Using computational modeling, we compared mechanistic hypotheses about thermal learning.

Method: Participants learned auditory-thermal cue-stimulus associations of varying strength. On each trial, participants heard an auditory cue and predicted the upcoming stimulus (i.e., cold or warm). Cue-stimulus contingencies were intermixed with TGI trials consisting of simultaneous cold and warm stimulation. On 50% of trials, participants provided subjective ratings indicating their cold, warm and burning sensations. Individual learning trajectories were fitted to participants’ trial-wise expectations using a hierarchical Bayesian approach.

Results: Results showed that when a stimulus is correctly anticipated, perception was amplified, and conversely, that incongruent expectations suppress felt thermosensation. Participants’ burning responses to TGI stimuli increased as the uncertainty in the association between the cue and the stimulus increased. An individual differences analysis showed that the surprise-related subjective intensity shifts were highly related between cold and warm modality. Furthermore, the sensitivity to illusory pain was interrelated to the degree to which TGI stimuli were modulated by expectations.

Conclusion: Our results demonstrate that healthy participants update their beliefs about thermal stimuli in a manner consistent with hierarchical Bayesian learning. We showed that both innocuous and illusory thermal percepts are modulated by expectations, and that susceptibility to these top-down effects is stable across thermal stimuli. Critically, the painful burning sensation elicited by the TGI was shown to be modulated by higher level uncertainties about the upcoming stimulus. These findings challenge strictly bottom-up accounts of the TGI to proffer a new understanding of both veridical and illusory thermal perception.

The Construction of Pain: Linking Psychological Factors to Pain thresholds (#76)

Böhme, Rebecca Astrid¹ Banellis, Leah², Allen, Micah², Fardo, Francesca²

¹Aarhus University, Aarhus, Denmark

²Aarhus University, Center of Functionally Integrative Neuroscience, Aarhus, Denmark

Original Experimental study

Aims: Previous studies found associations between psychological factors such as negative affect, depression, stress, fatigue, and quality of life and pain perception. However, these associations were investigated in isolation and often with small sample sizes. Here we addressed these issues by implementing multivariate latent variable modeling in a large sample, allowing us to compare patterns of inter-relation between these psychological factors and link them to thermal pain sensitivity.

Method: Using a Structural Equation Modeling approach together with linear regression analyses, we constructed statistical models assessing the interrelationship of pain thresholds, negative affect, depression, stress, fatigue, and quality of life in a large (n = 270) cohort of healthy participants. Based on the developed model, factor scores were used to categorize participants and examine their individual mental & physical well-being state (MPWB) in relation to their thermal pain thresholds (PS).

Results: The results do not provide any evidence that the psychological factors, as single variables or as a common construct, can predict thermal pain thresholds. Neither participants in a negative state of mental and physical well-being, nor participants in a positive state exhibited a change in pain sensitivity (Linear Regression: PS ∼ MPWB p = 0.328; Bayes Factor: BF = 0.211). These results urge caution in the assumption that laboratory pain thresholds may be related to psychological factors.

Conclusion: Since the developed MPWB model seems promising in representing the investigated psychological factors, it could be meaningful to relate the model to other pain specific experiences, which have explanatory value for the development of e.g., chronic pain. This approach has the potential to identify patient groups, who show a higher vulnerability to develop chronic pain.

Capillary isoelectric focusing immunoassay for detection of inflammatory protein biomarkers in plasma from individuals with chronic pain conditions (#79)

Wåhlén, Karin¹ Carlsson, Anders², Jiménez Cot, Natàlia², Ghafouri, Bijar²

¹Pain and Rehabilitation Center, Linköping University, Linköping, Sweden

²Division of Prevention, Rehabilitation and Community Medicine (PRNV), Linköping University, Linköping, Sweden

Original Experimental study

Aims: Chronic pain condition is a worldwide challenge where the molecular mechanisms are not fully elucidated. Proteomic studies on chronic pain have shown altered levels of inflammatory proteins and suggest an involvement of low-grade inflammation in chronic pain conditions. The aim of this study was to optimize a method to measure the inflammatory proteins complement C3, gelsolin, and transthyretin in the blood from patients with different chronic pain conditions.

Method: Capillary isoelectric focusing immunoassay (CIEF) (ProteinSimple^®) was used, which is a technique that allows separation of proteins by size or charge, by migration through capillaries, detected by antibodies, and visualized through chemiluminescence. This study focused on targeting the molecular weight of the proteins complement C3, gelsolin, and transthyretin. Four different plasma samples from chronic pain patients were evaluated: 1) crude sample, (2) depleted from albumin and immunoglobulin G, (3) desalted and a (4) both desalted and depleted. The total protein concentration (0.3 µg/ml–2 mg/ml), antibody dilution (1:10–1:2000) and saturation, and different type of buffers (PBS, ammonium bicarbonate, bicine/CHAPS) were optimized. Data was processed by the Compass software version 5.0.1 (ProteinSimple^®).

Results: The result showed that crude plasma samples, the bicine/CHAPS buffer, and a total protein concentration of 0.3 mg/ml (complement C3) and 2 mg/ml (gelsolin, transthyretin) was the most optimal choice to use for CIEF. The antibodies reached saturation at dilutions 1:200 (complement C3), 1:10 (gelsolin), and 1:25 (transthyretin). For each protein several peaks were detected suggesting that different molecular weight proteoforms are present in plasma.

Conclusion: This study shows that CIEF is a useful tool to investigate proteoforms in plasma. This optimized method could be used to target potential inflammatory protein biomarkers in plasma from chronic pain patients in future studies.

Usability of a serious game to teach surgical patients about postoperative pain management (#81)

Zoëga, Sigridur¹, Ingadottir, Brynja⁴ Blöndal, Katrin², Fossberg Thorlacius, Sigridur³

¹University of Iceland; Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland

²Landspítali University Hospital, Reykjavík, Iceland

³University of Iceland, Reykjavík, Iceland

⁴University of Iceland; Landspítali University Hospital, Reykjavík, Iceland

Original Experimental study

Aims: To evaluate the ease of use and usefulness of a serious game designed to help patients learn about postoperative pain management.

Method: This was an observational, pilot study. The sample consisted of people ≥18 years who were scheduled for abdominal surgery at Landspítali University Hospital. Data were collected with direct observations, questionnaires, and semi-structured interviews. Participants played a prototype of a serious game, then answered the Postoperative Pain Management Game Survey (POP-MSG) that measures perceived ease of use and usefulness of a simulation software, and the design of its interface. Response options range from 0 (strongly disagree) to 5 (strongly agree), reflecting higher usefulness and ease of use. The participants were finally interviewed about their experience and views about this learning method. Qualitative data analysis is ongoing, but here we report on the usability measurements.

Results: The participants (N=19; median age 40 years, range 24–68 years; 11 female) rated the usability and ease of use of the game high, as all items scored three or higher on the 0–5 scale. Everyone found it easy to start or stop the game, 79% found the activity easy to follow and the quality of the video good, and 89% rated the game as fun to play. In the usefulness part, 84% agreed that the game might encourage them to learn about postoperative pain management, and everyone agreed with the game being a useful adjunct to other pain management learning methods. Technical issues and the ease of navigating the game were the items that 42% and 32% of the participants, respectively, found problematic.

Conclusion: The game was rated as useful and easy to use but testing on a larger sample is needed to further test the usability and effectiveness of the game.