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  • 1.
    Ahlstrand, I.
    et al.
    School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. School of Health Sciences, Jönköping University, Jönköping, Sweden; School of Occupational Therapy and Social Work, CHIRI, Curtin University, Perth, WA, Australia.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Björk, Mathilda
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Rehabilitation Center. School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Pain and activity limitations in women and men with contemporary treated early RA compared to 10 years ago: the Swedish TIRA project2015In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, no 4, p. 259-264Article in journal (Refereed)
    Abstract [en]

    Objectives: To study differences regarding pain and activity limitations during the 3 years following diagnosis in women and men with contemporary treated early RA compared with their counterparts who were diagnosed 10 years earlier. Method: This study was based on patients recruited to the Early Intervention in RA (TIRA) project. In the first cohort (TIRA-1) 320 patients were included in time for diagnosis during 1996-1998 and 463 patients were included in the second cohort (TIRA-2) during 2006-2009. Disease activity, pain intensity (Visual Analogue Scale, VAS), bodily pain (BP) in the 36-item Short Form Health Survey (SF-36), activity limitations (Health Assessment Questionnaire, HAQ), and medication were reported at inclusion and at follow-up after 1, 2, and 3 years. Results: Disease activity, pain, and activity limitations were pronounced at inclusion across both genders and in both cohorts, with some improvement observed during the first year after diagnosis. Disease activity did not differ between cohorts at inclusion but was significantly lower at the follow-ups in the TIRA-2 cohort, in which the patients were prescribed traditional disease-modifying anti-rheumatic drugs (DMARDs) and biological agents more frequently. In TIRA-2, patients reported significantly lower pain and activity limitations at all follow-ups, with men reporting lower pain than women. Women reported significantly higher activity limitations at all time points in TIRA-2. Conclusions: Pain and activity limitations were still pronounced in the contemporary treated early RA cohort compared with their counterparts diagnosed 10 years earlier and both of these factors need to be addressed in clinical settings.

  • 2.
    Ahlstrand, Inger
    et al.
    Jonköping University, Sweden.
    Björk, Mathilda
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Rehabilitation Center. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Jonköping University, Sweden.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Jonköping University, Sweden; Curtin University, Australia.
    Pain and difficulties performing valued life activities in women and men with rheumatoid arthritis2015In: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 34, no 8, p. 1353-1362Article in journal (Refereed)
    Abstract [en]

    This study aimed to examine the difficulties with performing valued life activities in relation to pain intensity in women and men with rheumatoid arthritis (RA). In total, 737 persons with RA (73 % women) from three rheumatology units in Sweden responded to a questionnaire measuring performance of 33 valued life activities and self-rated pain. The relationships between performance of valued life activities (VLAs) and pain (measured by visual analogue scale (VAS)) were analysed based on gender. Multiple linear regression analyses were conducted with the total VLA score as dependent variable. Women reported more pain and difficulties in performing valued life activities than men. Across genders, 85 % reported at least one valued life activity affected by RA. Significantly more women than men encountered difficulties in performing some activities such as cooking, gardening and meeting new people. Women reported higher pain intensity (35 mm) than men (31 mm). Almost all 33 difficulty ratings for valued life activities were higher among persons with high pain (greater than 40 mm) than persons with lower pain. Difficulty ratings for valued life activities correlated positively with pain in persons with lower pain, but not among those with high pain. The results highlight the importance of addressing pain, especially among women with RA, as they reported pain to impact on their valued life activities. Interestingly, this was evident also in women with lower levels of pain.

  • 3.
    Ahlstrand, Inger
    et al.
    School of Health and Welfare, Jönköping University, Jönköping, Sweden.
    Vaz, Sharmila
    School of Occupational Therapy & Social Work, CHIRI, Curtin University, Perth, WA, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. School of Health and Welfare, Jönköping University, Jönköping, Sweden.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Björk, Mathilda
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Self-efficacy and pain acceptance as mediators of the relationship between pain and performance of valued life activities in women and men with rheumatoid arthritis2017In: Clinical Rehabilitation, ISSN 0269-2155, E-ISSN 1477-0873, Vol. 31, no 6, p. 824-834Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study whether personal factors (self-efficacy and pain acceptance) mediate the relationship between pain and performance of valued life activities in persons with rheumatoid arthritis.

    METHODS: Persons with rheumatoid arthritis for at least four years (n = 737; 73% women) answered a questionnaire measuring self-efficacy, pain acceptance, performance of valued life activities, and self-rated pain. Relationships among these constructs were explored using univariate and multivariate analyses. Structural equation modelling was then used to examine the mediational role of personal factors on the relationship between pain and performance of valued life activities.

    RESULTS: A direct negative association between pain and performance of valued life activities was identified (Beta = .34, P < .001). This suggests that people with rheumatoid arthritis who had higher levels of pain has increased difficulties in performing valued life activities. Self-efficacy and activity engagement component of pain acceptance mediated the relationship between pain and performance of valued life activities, however the pain willingness component of pain acceptance did not influence participation in valued life activities.

    CONCLUSION: These findings highlight the importance of considering personal factors, such as pain acceptance and self-efficacy, in facilitating participation in valued life activities.

  • 4.
    Alföldi, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Dragioti, Elena
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Wiklund, Tobias
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    SPREADING OF PAIN AND INSOMNIA IN PATIENTS WITH CHRONIC PAIN: RESULTS FROM A NATIONAL QUALITY REGISTRY (SQRP)2017In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 49, no 1, p. 63-70Article in journal (Refereed)
    Abstract [en]

    Objective: To explore how demographics, pain, psychosocial factors and insomnia relate to the spread of chronic pain. Methods: The study included 708 patients (68% women; median age 46 years; interquartile range 3557 years) with chronic pain who were referred to a multidisciplinary pain centre. Spreading of pain was assessed using a questionnaire covering 36 anatomically predefined pain regions. Data were collected on demographics, pain symptoms, psychological distress, and insomnia (Insomnia Severity Index). Four sub-categories of chronic pain were established: chronic local pain, chronic regional pain medium, chronic regional pain heavy, and chronic widespread pain. Results: The median number of pain regions was 10 (interquartile range 6-18). Prevalence of chronic pain was as follows: chronic local pain 9%, chronic regional pain medium 21%, chronic regional pain heavy 39%, and chronic widespread pain 31%. In the regression models, being a woman and persistent pain duration had the strongest associations with spreading of pain, but anxiety, pain interference, and insomnia were also important factors. Conclusion: Spreading of chronic pain can only partly be explained by the simultaneous levels of insomnia. Female sex, pain duration, pain interference and anxiety appear to have more significant relationships with the spread of pain. Targeting these factors may lead to improvements in treatment and prevention strategies.

  • 5.
    Almberg, Maria
    et al.
    Mobil Centre Gothenburg, Sweden.
    Selander, Helena
    Mobil Centre Gothenburg, Sweden; University of Gothenburg, Sweden.
    Falkmer, Marita
    Curtin University, Australia; Jonköping University, Sweden.
    Vaz, Sharmila
    Curtin University, Australia.
    Ciccarelli, Marina
    Curtin University, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Australia.
    Experiences of facilitators or barriers in driving education from learner and novice drivers with ADHD or ASD and their driving instructors2017In: Developmental Neurorehabilitation, ISSN 1751-8423, E-ISSN 1751-8431, Vol. 20, no 2, p. 59-67Article in journal (Refereed)
    Abstract [en]

    Background: Little is known about whether individuals with autism spectrum disorder (ASD) or attention deficit hyperactive disorder (ADHD) experience any specific facilitators or barriers to driving education. Objective: To explore the facilitators or barriers to driving education experienced by individuals with ASD or ADHD who obtained a learners permit, from the perspective of the learner drivers and their driving instructors. Methods: Datawere collected from33 participants with ASD or ADHD, and nine of their driving instructors. Results: Participants with ASD required twice asmany driving lessons andmore on-road tests than those with ADHD. Participants with ADHD repeated the written tests more than those with ASD. Driving license theory was more challenging for individuals with ADHD, whilst individuals with ASD found translating theory into practice and adjusting to "unfamiliar driving situations to be the greatest challenges. Conclusion: Obtaining a driving license was associated with stressful training experience.

  • 6.
    Bajramaj, Ermira
    et al.
    Malmo Univ, Sweden.
    Haggman-Henrikson, Birgitta
    Malmo Univ, Sweden; Umea Univ, Sweden.
    Dawson, Andreas
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Public Dental Health Care, Center for Oral Rehabilitation Norrköping. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    The Effect of Microdialysis Catheter Insertion on Glutamate and Serotonin Levels in Masseter Muscle in Patients with Myofascial Temporomandibular Disorders and Healthy Controls2019In: Diagnostics (Basel), ISSN 2075-4418, Vol. 9, no 1, article id 14Article in journal (Refereed)
    Abstract [en]

    Myofascial temporomandibular disorders (TMD) are the most common cause of chronic pain in the orofacial region. Microdialysis has been used to study metabolic changes in the human masseter muscle. The insertion of the microdialysis probe causes acute tissue trauma that could affect the metabolic milieu and thereby influence the results when comparing healthy subjects to those with TMD. This study aimed to investigate the levels of serotonin and glutamate during the acute tissue trauma period in healthy subjects and in patients with TMD. Microdialysis was carried out in 15 patients with TMD and 15 controls, and samples were collected every 20 min during a period of 140 min. No significant alterations of serotonin or glutamate were observed over the 2 h period for the healthy subjects. For the TMD group, a significant decrease in serotonin was observed over time (p amp;lt; 0.001), followed by a significant increase between 120 and 140 min (p amp;lt; 0.001). For glutamate, a significant reduction was observed at 40 min compared to baseline. The results showed that there was a spontaneous increase of serotonin 2 h after the insertion of the catheter in patients with TMD. In conclusion, the results showed that there are differences in the masseter muscle levels of serotonin and glutamate during acute nociception in patients with myofascial TMD compared to healthy subjects.

  • 7.
    Bendelin, Nina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Inst, Sweden.
    Internet-delivered aftercare following multimodal rehabilitation program for chronic pain: a qualitative feasibility study2018In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 11, p. 1715-1728Article in journal (Refereed)
    Abstract [en]

    Purpose: Methods for delivering aftercare to help chronic pain patients to continue practice self-management skills after rehabilitation are needed. Internet-delivered cognitive behavioral therapy (ICBT) has the potential to partly fill this gap given its accessibility and emphasis on self-care. Methods for engaging and motivating patients to persist throughout the full length of treatment are needed. The aim of this study was to describe how chronic pain patients work in an ICBT program, through their descriptions of what is important when they initiate behavior change in aftercare and their descriptions of what is important for ongoing practice of self-management skills in aftercare. Patients and methods: Following a multimodal rehabilitation program, 29 chronic pain patients participated in a 20-week-long Internet-delivered aftercare program (ACP) based on acceptance-based cognitive behavioral therapy. Latent content analysis was made on 138 chapters of diary-like texts written by participants in aftercare. Results: Attitudes regarding pain and body changed during ACP, as did attitudes toward self and the future for some participants. How participants practiced self-management skills was influenced by how they expressed motivation behind treatment goals. Whether they practiced acceptance strategies influenced their continuous self-management practice. Defusion techniques seemed to be helpful in the process of goal setting. Mindfulness strategies seemed to be helpful when setbacks occurred. Conclusion: Self-motivating goals are described as important both to initiate and in the ongoing practice of self-management skills. Experiencing a helpful effect of acceptance strategies seems to encourage participants to handle obstacles in new ways and to persist throughout treatment. Research on whether tailored therapist guidance might be helpful in stating self-motivating goals and contribute to ongoing practice of self-management skills is needed.

  • 8.
    Bergström, Maria
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Linköping University, Faculty of Medicine and Health Sciences.
    Ahlstrand, Inger
    Jönköping University, Sweden.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Jonköping University, Sweden; Curtin University, Australia.
    Börsbo, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Björk, Mathilda
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Like the worst toothache you've had - How people with rheumatoid arthritis describe and manage pain2017In: Scandinavian Journal of Occupational Therapy, ISSN 1103-8128, E-ISSN 1651-2014, Vol. 24, no 6, p. 468-476Article in journal (Refereed)
    Abstract [en]

    Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease often associated with disability. Despite new treatments, pain and activity limitations are still present. Objectives: To describe how persons with RA experience and manage pain in their daily life. Methods: Seven semi-structured focus groups (FGs) were conducted and analyzed using content analysis. Results: The analysis revealed four categories: 1) Pain expresses itself in different ways referred to pain as overwhelming, aching or as a feeling of stiffness. 2) Mitigating pain referred to the use of heat, cold, medications and activities as distractions from the pain. 3) Adapting to pain referred to strategies employed as coping mechanisms for the pain, e.g. planning and adjustment of daily activities, and use of assistive devices. 4) Pain in a social context referred to the participants social environment as being both supportive and uncomprehending, the latter causing patients to hide their pain. Conclusions: Pain in RA is experienced in different ways. This emphasizes the multi-professional team to address this spectrum of experiences and to find pain management directed to the individual experience that also include the persons social environment.

  • 9.
    Bernfort, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    People in states worse than dead according to the EQ-5D UK value set: would they rather be dead?2018In: Quality of Life Research, ISSN 0962-9343, E-ISSN 1573-2649, Vol. 27, no 7, p. 1827-1833Article in journal (Refereed)
    Abstract [en]

    Quality-adjusted life years (QALYs) measure health by combining length and quality of life. QALYs constitute the effect side of incremental cost-effectiveness ratios, describing the results of health economic evaluations. The objectives of this study were to (1) investigate the prevalence of states worse than dead (SWD) when using the EuroQol-5D UK value set, and (2) to study to what extent SWDs are reasonable with a starting point in experience-based valuations of health states. Data from a Swedish cross-sectional population survey were used. The survey was directed to 10,000 persons 65 years and older and its primary aim was to investigate the prevalence and consequences of chronic pain. The survey included questions reflecting life situation and well-being. Some of these were used in order to characterise people in SWD. SWD were found in 1.8% of the 6611 respondents. The prevalence of SWD increased with advancing age and was more common among women than men. The control questions used indicated that most of the persons being in SWD according to the EQ-5D UK value set most probably would not judge themselves to be in a SWD. Though negative QALY-weights are not very common, they constitute a non-negligible part of health states in a Swedish population 65 years and older. Prevalence of SWD is higher among women than men and increases with age. From responses to other questions on well-being and life situation, there is reason to doubt the reasonableness of experience-based negative QALY-weights in many cases.

  • 10.
    Bernfort, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Rahmqvist, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Chronic pain in an elderly population in Sweden: Impact on costs and quality of life2015Report (Other academic)
    Abstract [en]

    Chronic pain among elderly people has long been a well-known problem, in terms of both societal costs and the quality of life of affected individuals. To estimate the magnitude of the problems associated with chronic pain in an elderly population, data on both costs and quality of life were gathered. A postal questionnaire was sent out to a stratified sample of 10 000 inhabitants 65 years and older in Linköping and Norrköping. The survey included questions on demographics, habits, and life situation, and different kinds of questions and instruments related to well-being (e.g., quality-of-life and pain-specific questions). In the questionnaire respondents were asked whether they were receiving any help—informal care—from a relative. If they answered yes, they were asked for permission to contact the informal caregiver and to provide contact details. The amount of informal care provided by relatives to persons with chronic pain was investigated by use of a questionnaire directed to the caregiving relatives, containing questions about time spent providing informal care.

    Data on costs were collected from registers of consumption of health care, drugs, and municipal services.

    The results of the study showed a very clear association between existence and severity of chronic pain and societal costs. The study population was subdivided into three groups with respect to having chronic pain or not, and a pain intensity during the last week of 0–4 (mild), 5–7 (moderate), or 8–10 (severe) on a scale of 0–10. Taking all costs (health care, drugs, municipal services, and informal care) into account, persons in the severe chronic pain group consumed on average 72% more resources than persons in the moderate chronic pain group and 143% more than those in the no or mild chronic pain group. Differences were most pronounced concerning municipal services and informal care costs.

    Even more alarming are the results on the quality of life of persons in the different groups. On the EQ-5D index, the average value for persons in the no or mild chronic pain group was 0.82. For those in the moderate chronic pain group the average value was 0.64, and for those in the severe chronic pain group the average value was only 0.38. EQ-VAS resulted in less pronounced but still clearly significant differences.

    It is concluded that this study, reaching a rather large part of the target population, shows that existence and severity of chronic pain among people 65 years and older affects costs to society and the quality of life of affected individuals in a massive way.

  • 11.
    Bernfort, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Rahmqvist, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Severity of chronic pain in an elderly population in Sweden-impact on costs and quality of life2015In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 156, no 3, p. 521-527Article in journal (Refereed)
    Abstract [en]

    Chronic pain is associated with large societal costs, but few studies have investigated the total costs of chronic pain with respect to elderly subjects. The elderly usually require informal care, care performed by municipalities, and care for chronic diseases, all factors that can result in extensive financial burdens on elderly patients, their families, and the social services provided by the state. This study aims to quantify the societal cost of chronic pain in people of age 65 years and older and to assess the impact of chronic pain on quality of life. This study collected data from 3 registers concerning health care, drugs, and municipal services and from 2 surveys. A postal questionnaire was used to collect data from a stratified sample of the population 65 years and older in southeastern Sweden. The questionnaire addressed pain intensity and quality of life variables (EQ-5D). A second postal questionnaire was used to collect data from relatives of the elderly patients suffering from chronic pain. A total of 66.5% valid responses of the 10,000 subjects was achieved; 76.9% were categorized as having no or mild chronic pain, 18.9% as having moderate chronic pain, and 4.2% as having severe chronic pain. Consumed resources increased with the severity of chronic pain. Clear differences in EQ-5D were found with respect to the severity of pain. This study found an association between resource use and severity of chronic pain in elderly subjects: the more severe the chronic pain, the more extensive (and expensive) the use of resources.

  • 12.
    Bernfort, Lars
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Chronic pain in a population 65 years and older: correlation with age of health care costs and quality of life2015Conference paper (Refereed)
  • 13.
    Bileviciute-Ljungar, Indre
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Danderyd University Hospital, Karolinska Institutet, Sweden.
    Maroti, Daniel
    Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet; and ME/CFS-rehabilitation, Department of Rehabilitation Medicine, Danderyd University Hospital, Stockholm, Sweden.
    Bejerot, Susanne
    Department of Medical Sciences, Örebro University, Örebro, Sweden.
    Patients with chronic fatigue syndrome do not score higher on the autism-spectrum quotient than healthy controls: Comparison with autism spectrum disorder2018In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 59, no 4, p. 428-432Article in journal (Refereed)
    Abstract [en]

    Clinically, there is an overlap of several symptoms of chronic fatigue syndrome (CFS) and autism spectrum disorder (ASD), including fatigue; brain "fog"; cognitive impairments; increased sensitivity to sound, light, and odour; increased pain and tenderness; and impaired emotional contact. Adults with CFS (n = 59) or ASD (n = 50) and healthy controls (HC; n = 53) were assessed with the Autism-Spectrum Quotient (AQ) in a cross-sectional study. Non-parametric analysis was used to compare AQ scores among the groups. Univariate analysis of variance (ANCOVA) was used to identify if age, sex, or diagnostic group influenced the differences in scores. Patients with ASD scored significantly higher on the AQ than the CFS group and the HC group. No differences in AQ scores were found between the CFS and HC groups. AQ results were influenced by the diagnostic group but not by age or sex, according to ANCOVA. Despite clinical observations of symptom overlap between ASD and CFS, adult patients with CFS report few autistic traits in the self-report instrument, the AQ. The choice of instrument to assess autistic traits may influence the results.

  • 14.
    Biurrun Manresa, Jose A.
    et al.
    Aalborg University, Denmark.
    Sörensen, Jan
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Faculty of Medicine and Health Sciences.
    Andersen, Ole K.
    Aalborg University, Denmark.
    Arendt-Nielsen, Lars
    Aalborg University, Denmark.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Dynamic Changes in Nociception and Pain Perception After Spinal Cord Stimulation in Chronic Neuropathic Pain Patients2015In: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 31, no 12, p. 1046-1053Article in journal (Refereed)
    Abstract [en]

    Objectives: Patients with an implanted spinal cord stimulation (SCS) system for pain management present an opportunity to study dynamic changes in the pain system in a situation where patients are not stimulated (ie, experiencing severe pain) compared with a situation in which patients have just been stimulated (ie, pain free or greatly reduced pain). The aims of this study were (1) to determine if there are differences in nociceptive withdrawal reflex thresholds (NWR-T) and electrical pain thresholds (EP-T) before and after SCS; and (2) to establish if these differences are related to psychological factors associated with chronic pain. Methods: Seventeen volunteers with chronic neuropathic pain participated in the experiment. Electrical stimuli were applied to assess the NWR-T and the EP-T. In addition, psychological factors (ie, pain characteristics, depression, anxiety, and disability indexes) were also recorded. The NWR-T and EP-T were assessed with the SCS system off (at least 8 h before the experiment), and then reassessed 1 hour after the SCS system was turned on. Results: Ongoing pain intensity ratings decreased (P=0.018), whereas the NWR-T increased (P=0.028) after the SCS was turned on, whereas no significant difference was found for EP-T (P=0.324). Psychological factors were significant predictors for EP-T but not for NWR-T. Discussion: The results of this study suggest that pain relief after SCS is partially mediated by a decrease in the excitability of dorsal horn neurons in the spinal cord.

  • 15.
    Bjersing, Jan L.
    et al.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Larsson, Anette
    University of Gothenburg, Sweden.
    Palstam, Annie
    University of Gothenburg, Sweden.
    Ernberg, Malin
    Karolinska Institute, Sweden.
    Bileviciute-Ljungar, Indre
    Karolinska Institute, Sweden.
    Löfgren, Monika
    Karolinska Institute, Sweden.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Kosek, Eva
    Karolinska Institute, Sweden; Stockholm Spine Centre, Sweden.
    Mannerkorpi, Kaisa
    University of Gothenburg, Sweden; Sahlgrenska University Hospital, Sweden.
    Benefits of resistance exercise in lean women with fibromyalgia: involvement of IGF-1 and leptin2017In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 18, article id 106Article in journal (Refereed)
    Abstract [en]

    Background: Chronic pain and fatigue improves by exercise in fibromyalgia (FM) but underlying mechanisms are not known. Obesity is increased among FM patients and associates with higher levels of pain. Symptom improvement after aerobic exercise is affected by body mass index (BMI) in FM. Metabolic factors such as insulin-like growth factor 1 (IGF1) and leptin may be involved. In this study, the aim was to evaluate the role of metabolic factors in lean, overweight and obese women during resistance exercise, in relation to symptom severity and muscle strength in women with FM. Methods: Forty-three women participated in supervised progressive resistance exercise, twice weekly for 15-weeks. Serum free and total IGF-1, IGF-binding protein 3 (IGFBP3), adiponectin, leptin and resistin were determined at baseline and after 15-weeks. Level of current pain was rated on a visual analogue scale (0-100 mm). Level of fatigue was rated by multidimensional fatigue inventory (MFI-20) subscale general fatigue (MFIGF). Knee extension force, elbow flexion force and handgrip force were assessed by dynamometers. Results: Free IGF-1 (p = 0.047), IGFBP3 (p = 0.025) and leptin (p = 0.008) were significantly decreased in lean women (n = 18), but not in the overweight (n = 17) and the obese (n = 8). Lean women with FM benefited from resistance exercise with improvements in current pain (p= 0.039, n = 18), general fatigue (MFIGF, p = 0.022, n = 18) and improved elbow-flexion force (p = 0.017, n = 18). In overweight and obese women with FM there was no significant improvement in pain or fatigue but an improvement in elbow flexion (p = 0.049; p = 0.012) after 15 weeks of resistance exercise. Conclusion: The clearest clinical response to resistance exercise was found in lean patients with FM. In these individuals, individualized resistance exercise was followed by changes in IGF-1 and leptin, reduced pain, fatigue and improved muscular strength. In overweight and obese women FM markers of metabolic signaling and clinical symptoms were unchanged, but strength was improved in the upper limb. Resistance exercise combined with dietary interventions might benefit patients with FM and overweight.

  • 16.
    Black, Melissa H.
    et al.
    Curtin Univ, Australia.
    Mandi, Soheil
    Karolinska Inst, Sweden; Stockholm Hlth Care Serv, Sweden.
    Milbourn, Benjamin
    Curtin Univ, Australia.
    Thompson, Craig
    Curtin Univ, Australia.
    DAngelo, Axel
    Karolinska Inst, Sweden; Stockholm Hlth Care Serv, Sweden.
    Strom, Eva
    Swedish Publ Employment Serv, Sweden.
    Falkmer, Marita
    Curtin Univ, Australia; Jonkoping Univ, Sweden.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin Univ, Australia.
    Lerner, Matthew
    SUNY Stony Brook, NY 11794 USA.
    Halladay, Alycia
    Autism Sci Fdn, NY USA.
    Gerber, Alan
    SUNY Stony Brook, NY 11794 USA.
    Esposito, Christopher
    SUNY Stony Brook, NY 11794 USA.
    Girdler, Sonya
    Curtin Univ, Australia; Curtin Univ, Australia.
    Bolte, Sven
    Curtin Univ, Australia; Karolinska Inst, Sweden; Stockholm Hlth Care Serv, Sweden; Stockholm Hlth Care Serv, Sweden.
    Perspectives of key stakeholders on employment of autistic adults across the united states, australia, and sweden2019In: Autism Research, ISSN 1939-3792, E-ISSN 1939-3806Article in journal (Refereed)
    Abstract [en]

    Despite efforts to improve employment outcomes for autistic individuals, internationally their employment rates remain low. There is a need to better understand the factors influencing successful employment for autistic adults in the labor market from the perspectives of multiple key stakeholders. This study represents the second in a series of papers conducted as part of an International Society for Autism Research policy brief aimed at improving employment outcomes for autistic individuals. A community consultation methodology using focus groups, forums, and interviews was applied with autistic individuals (n = 19), family members (n = 18), service providers (n = 21), employers (n = 11), researchers (n = 5), and advocacy group representatives (n = 5) in Australia, Sweden, and the United States, aiming to identify the factors perceived to determine gaining and maintaining employment for autistic individuals. Directed content analysis, guided by the International Classification of Functioning, Disability and Health (ICF), was conducted to investigate the key factors influencing employment outcomes for autistic individuals. Meaningful verbal concepts, or units of text with common themes, were also derived from the qualitative data and then linked and compared to the ICF Autism Spectrum Disorder (ASD) Core-sets. Across countries, activity and participation and environmental factor categories of the ICF were the most associated with employment outcomes. Results suggest that removal of environmental barriers and enhancing environmental facilitators may assist to remediate ASD-related difficulties in the workplace. Autism Res 2019, (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary This study sought to understand the perspectives of autistic individuals and key stakeholders on factors influencing if autistic adults get and keep jobs. Across Australia, Sweden, and the United States, focus groups and interviews were conducted to understand international perspectives on what helps and hinders getting and keeping a job for autistic individuals. The environment, including supports, relationships, attitudes, and services, were perceived to be the most important for workplace success. Intervention targeting barriers and facilitators in the workplace environment may support autistic adults to be successful in the labor market.

  • 17.
    Black, Melissa H.
    et al.
    Curtin Univ, Australia.
    Vaz, Sharmila
    Curtin Univ, Australia.
    Parsons, Richard
    Curtin Univ, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin Univ, Australia.
    Tang, Julia S. Y.
    Curtin Univ, Australia.
    Morris, Susan
    Curtin Univ, Australia.
    Lee, Hoe
    Curtin Univ, Australia.
    Falkmer, Marita
    Curtin Univ, Australia; Jonkoping Univ, Sweden.
    Disembedding performance and eye gaze behavior of adolescents with Autism Spectrum Disorder2019In: Research in Autism Spectrum Disorders, ISSN 1750-9467, E-ISSN 1878-0237, Vol. 66, article id UNSP 101417Article in journal (Refereed)
    Abstract [en]

    Background: Atypical visual perception in individuals with Autism Spectrum Disorders (ASD) may contribute to superiority in disembedding tasks. Gaze behavior has provided some insights in to mechanisms underlying this purported superiority in children, however evidence is limited and requires additional investigation. Method: The performance and gaze behavior of 27 adolescents with ASD and 27 matched typically developing (TD) peers were examined during the Figure Ground Subtest of the Test of Visual Perception Skills-third edition (TVPS-3). Results: Compared to their TD counterparts, adolescents with ASD were no different in accuracy, however, had a longer response time. Differences in gaze behavior were also observed, characterized by adolescents with ASD spending less time viewing the incorrect and target figures, and spending a greater proportion of time viewing irrelevant areas of the stimuli compared to TD adolescents. Conclusions: Results suggest that while altered visual perception was observed, this did not contribute to superiority in disembedding tasks in adolescents with ASD. Future research is required to elucidate conditions under which altered visual perception may contribute to behavioral superiority.

  • 18.
    Blane, Alison
    et al.
    Curtin Univ, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin Univ, Australia; Jonkoping Univ, Sweden; La Trobe Univ, Australia.
    Lee, Hoe C.
    Curtin Univ, Australia.
    Dukic Willstrand, Tania
    Swedish Natl Rd and Transport Res Inst VTI, Sweden.
    Investigating cognitive ability and self-reported driving performance of post-stroke adults in a driving simulator2018In: Topics in Stroke Rehabilitation, ISSN 1074-9357, E-ISSN 1945-5119, Vol. 25, no 1, p. 44-53Article in journal (Refereed)
    Abstract [en]

    Background: Safe driving is a complex activity that requires calibration. This means the driver can accurately assess the level of task demand required for task completion and can accurately evaluate their driving capability. There is much debate on the calibration ability of post-stroke drivers. Objectives: The aim of this study was to assess the cognition, self-rated performance, and estimation of task demand in a driving simulator with post-stroke drivers and controls. Methods: A between-groups study design was employed, which included a post-stroke driver group and a group of similarly aged older control drivers. Both groups were observed driving in two simulator-based driving scenarios and asked to complete the NASA Task Load Index (TLX) to assess their perceived task demand and self-rate their driving performance. Participants also completed a battery of psychometric tasks to assess attention and executive function, which was used to determine whether post-stroke cognitive impairment impacted on calibration. Results: There was no difference in the amount of perceived task demand required to complete the driving task. Despite impairments in cognition, the post-stroke drivers were not more likely to over-estimate their driving abilities than controls. On average, the post-stroke drivers self-rated themselves more poorly than the controls and this rating was related to cognitive ability. Conclusion: This study suggests that post-stroke drivers may be aware of their deficits and adjust their driving behavior. Furthermore, using self-performance measures alongside a driving simulator and cognitive assessments may provide complementary fitness-to-drive assessments, as well as rehabilitation tools during post-stroke recovery.

  • 19.
    Blane, Alison
    et al.
    Curtin University, Australia.
    Lee, Hoe C.
    Curtin University, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Australia; Jonköping University, Sweden; La Trobe University, Australia.
    Dukic Willstrand, Tania
    Swedish National Rd and Transport Research Institute VTI, Sweden.
    Assessing Cognitive Ability and Simulator-Based Driving Performance in Poststroke Adults2017In: Behavioural Neurology, ISSN 0953-4180, E-ISSN 1875-8584, article id 1378308Article in journal (Refereed)
    Abstract [en]

    Driving is an important activity of daily living, which is increasingly relied upon as the population ages. It has been well-established that cognitive processes decline following a stroke and these processes may influence driving performance. There is much debate on the use of off-road neurological assessments and driving simulators as tools to predict driving performance; however, the majority of research uses unlicensed poststroke drivers, making the comparability of poststroke adults to that of a control group difficult. It stands to reason that in order to determine whether simulators and cognitive assessments can accurately assess driving performance, the baseline should be set by licenced drivers. Therefore, the aim of this study was to assess differences in cognitive ability and driving simulator performance in licensed community-dwelling poststroke drivers and controls. Two groups of licensed drivers (37 poststroke and 43 controls) were assessed using several cognitive tasks and using a driving simulator. The poststroke adults exhibited poorer cognitive ability; however, there were no differences in simulator performance between groups except that the poststroke drivers demonstrated less variability in driver headway. The application of these results as a prescreening toolbox for poststroke drivers is discussed.

  • 20.
    Blane, Alison
    et al.
    Curtin Univ, Australia.
    Lee, Hoe
    Curtin Univ, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin Univ, Australia; Jonkoping Univ, Sweden; La Trobe Univ, Australia.
    Willstrand, Tania Dukic
    Jonkoping Univ, Sweden; Swedish Natl Rd and Transport Res Inst VTI, Sweden.
    Cognitive ability as a predictor of task demand and self-rated driving performance in post-stroke drivers - Implications for self-regulation2018In: Journal of Transport and Health, ISSN 2214-1405, E-ISSN 2214-1405, Vol. 9, p. 169-179Article in journal (Refereed)
    Abstract [en]

    Driving is a highly complex task requiring multiple cognitive processes that can be adversely affected post-stroke. It is unclear how much ability post-stroke adults have to self-evaluate their driving performance. Furthermore, the impact of cognitive decline on this evaluation has not been previously investigated. The aim of this study was to investigate the perceived level of task demand involved in driving tasks, and to examine differences between perceived and observed driving performance in post-stroke drivers in comparison to a control group. A further aim of the research was to investigate the influence of cognition on self-rated driving performance. A total of 78 participants (35 post-stroke and 43 controls) were assessed using a series of cognitive tasks and were observed whilst driving. Participants were asked to rate their own driving performance and the task demand involved while driving using the NASA Task Load Index. Between group analyses were conducted to determine differences in the level of self-rated performance and task demand. Further analyses were conducted to investigate whether cognition accounted for differences in task demand or self-rated performance. Overall, the results suggested that the post-stroke drivers exhibited deficits in cognition, but they did not report increased levels of task demand when driving. Post-stroke adults also rated themselves more conservatively than the controls for on-road performance, which was associated with their reduced propensity for risk. The study suggests that cognitive deficits may influence post-stroke drivers to amend their driving behaviour, in order to bring the task demand within a manageable level. Understanding the mechanisms involved in self-rated performance and estimations of task demand can help promote accurate self-regulation practices in post-stroke drivers. Furthermore, measuring calibration may assist practitioners with assessing fitness-to-drive, as well as with tailoring driving rehabilitation.

  • 21.
    Blom, Kerstin
    et al.
    Karolinska Institute, Sweden.
    Tarkian Tillgren, Hanna
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Wiklund, Tobias
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Danlycke, Ewa
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Forssen, Mattias
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Söderström, Alexandra
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Johansson, Robert
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Hesser, Hugo
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Jernelov, Susanna
    Karolinska Institute, Sweden.
    Lindefors, Nils
    Karolinska Institute, Sweden.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Kaldo, Viktor
    Karolinska Institute, Sweden.
    Internet-vs. group-delivered cognitive behavior therapy for insomnia: A randomized controlled non-inferiority trial2015In: Behaviour Research and Therapy, ISSN 0005-7967, E-ISSN 1873-622X, Vol. 70, p. 47-55Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare guided Internet-delivered to group-delivered cognitive behavioral therapy (CBT) for insomnia. We conducted an 8-week randomized controlled non-inferiority trial with 6-months follow-up. Participants were forty-eight adults with insomnia, recruited via media. Interventions were guided Internet-delivered CBT (ICBT) and group-delivered CBT (GCBT) for insomnia. Primary outcome measure was the Insomnia Severity Index (ISI), secondary outcome measures were sleep diary data, depressive symptoms, response- and remission rates. Both treatment groups showed significant improvements and large effect sizes for ISI (Within Cohens d: ICBT post = 1.8, 6-months follow-up = 2.1; GCBT post = 2.1, 6-months follow-up = 2.2). Confidence interval of the difference between groups posttreatment and at FU6 indicated non-inferiority of ICBT compared to GCBT. At post-treatment, two thirds of patients in both groups were considered responders (ISI-reduction greater than 7p). Using diagnostic criteria, 63% (ICBT) and 75% (GCBT) were in remission. Sleep diary data showed moderate to large effect sizes. We conclude that both guided Internet-CBT and group-CBT in this study were efficacious with regard to insomnia severity, sleep parameters and depressive symptoms. The results are in line with previous research, and strengthen the evidence for guided Internet-CBT for insomnia. Trial registration: The study protocol was approved by, and registered with, the regional ethics review board in Linkoping, Sweden, registration number 2010/385-31.

  • 22.
    Boersma, Katja
    et al.
    Orebro Univ, Sweden.
    Södermark, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hesser, Hugo
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology.
    Flink, Ida K.
    Orebro Univ, Sweden.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Linton, Steven J.
    Orebro Univ, Sweden.
    Efficacy of a transdiagnostic emotion-focused exposure treatment for chronic pain patients with comorbid anxiety and depression: a randomized controlled trial2019In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 160, no 8, p. 1708-1718Article in journal (Refereed)
    Abstract [en]

    The comorbidity between chronic pain and emotional problems has proven difficult to address with current treatment options. This study addresses the efficacy of a transdiagnostic emotion-focused exposure treatment ("hybrid") for chronic pain patients with comorbid emotional problems. Adults (n = 115) with chronic musculoskeletal pain and functional and emotional problems were included in a 2-centre, parallel randomized controlled, open-label trial comparing this treatment to an active control condition receiving a guided Internet-delivered pain management treatment based on CBT principles (iCBT). The hybrid treatment (n = 58, 10-16 sessions) integrates exposure in vivo for chronic pain based on the fear-avoidance model with an emotion-regulation approach informed by procedures in Dialectical Behavior Therapy. The iCBT (n = 57; 8 treatment modules) addresses topics such as pain education, coping strategies, relaxation, problem solving, stress, and sleep management using standard CBT techniques. Patient-reported outcomes were assessed before and after treatment as well as at a 9-month primary end point. Across conditions, 78% participants completed post-treatment and 81% follow-up assessment. Intent-to-treat analyses showed that the hybrid had a significantly better post-treatment outcome on pain catastrophizing (d = 0.39) and pain interference (d = 0.63) and significantly better follow-up outcomes on depression (d = 0.43) and pain interference (d = 0.51). There were no differences on anxiety and pain intensity. Observed proportions of clinically significant improvement favoured the hybrid on all but one comparison, but no statistically significant differences were observed. We conclude that the hybrid emotion-focused treatment may be considered an acceptable, credible, and efficacious treatment option for chronic pain patients with comorbid emotional problems.

  • 23.
    Borgestig, Maria
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Folke Bernadotte Regional Habilitation Centre and Department of Women´s and Children´s Health, Uppsala University, Uppsala, Sweden.
    Sandqvist, Jan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy.
    Ahlsten, Gunnar
    Folke Bernadotte Regional Habilitation Centre and Department of Women´s and Children´s Health, Uppsala University, Uppsala, Sweden.
    Falkmer, Torbjorn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. School of Occupational Therapy & Social Work, Curtin University, Perth, WA, Australia; School of Occupational Therapy, La Trobe University, Melbourne, Victoria, Australia.
    Hemmingsson, Helena
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy.
    Gaze-based assistive technology in daily activities in children with severe physical impairments: an intervention study2017In: Developmental Neurorehabilitation, ISSN 1751-8423, E-ISSN 1751-8431, Vol. 20, no 3, p. 129-141Article in journal (Refereed)
    Abstract [en]

    Objective: To establish the impact of a gaze-based assistive technology (AT) intervention on activity repertoire, autonomous use, and goal attainment in children with severe physical impairments, and to examine parents’ satisfaction with the gaze-based AT and with services related to the gaze-based AT intervention.

    Methods: Non-experimental multiple case study with before, after, and follow-up design. Ten children with severe physical impairments without speaking ability (aged 1–15 years) participated in gaze-based AT intervention for 9–10 months, during which period the gaze-based AT was implemented in daily activities.

    Results: Repertoire of computer activities increased for seven children. All children had sustained usage of gaze-based AT in daily activities at follow-up, all had attained goals, and parents’ satisfaction with the AT and with services was high.

    Discussion: The gaze-based AT intervention was effective in guiding parents and teachers to continue supporting the children to perform activities with the AT after the intervention program.

  • 24.
    Borgestig, Maria
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Folke Bernadotte Regional Habilitation Centre and Department of Women´s and Children´s Health, Uppsala University, Uppsala, Sweden.
    Sandqvist, Jan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy.
    Parsons, Richard
    School of Occupational Therapy & Social Work, Curtin University, Perth, WA, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. School of Occupational Therapy & Social Work, Curtin University, Perth, WA, Australia / School of Occupational Therapy, La Trobe University, Melbourne, Victoria, Australia.
    Hemmingsson, Helena
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Linköping University, Faculty of Medicine and Health Sciences.
    Eye gaze performance for children with severe physical impairments using gaze-based assistive technology: a longitudinal study2016In: Assistive technology, ISSN 1040-0435, E-ISSN 1949-3614, Vol. 28, no 2, p. 93-102Article in journal (Refereed)
    Abstract [en]

    Gaze-based assistive technology (gaze-based AT) has the potential to provide children affected by severe physical impairments with opportunities for communication and activities. This study aimed to examine changes in eye gaze performance over time (time on task and accuracy) in children with severe physical impairments, without speaking ability, using gaze-based AT. A longitudinal study with an AB design was conducted on ten children (aged 1–15 years) with severe physical impairments, who were beginners to gaze-based AT at baseline. Thereafter, all children used the gaze-based AT in daily activities over the course of the study. Compass computer software was used to measure time on task and accuracy with eye selection of targets on screen, and tests were performed with the children at baseline, after 5 months, 9–11 months, and after 15–20 months. Findings showed that the children improved in time on task after 5 months and became more accurate in selecting targets after 15–20 months. This study indicates that these children with severe physical impairments, who were unable to speak, could improve in eye gaze performance. However, the children needed time to practice on a long-term basis to acquire skills needed to develop fast and accurate eye gaze performance.

  • 25.
    Bruce, C. R.
    et al.
    La Trobe University, Australia.
    Unsworth, C. A.
    La Trobe University, Australia; CQUniversity, Australia; Jonköping University, Sweden; Curtin University, Australia.
    Dillon, M. P.
    La Trobe University, Australia.
    Tay, R.
    RMIT University, Australia.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Australia.
    Bird, P.
    Gosforth Clin, Australia.
    Carey, L. M.
    La Trobe University, Australia; Florey Institute Neurosci and Mental Health Neurorehabil and, Australia.
    Hazard perception skills of young drivers with Attention Deficit Hyperactivity Disorder (ADHD) can be improved with computer based driver training: An exploratory randomised controlled trial2017In: Accident Analysis and Prevention, ISSN 0001-4575, E-ISSN 1879-2057, Vol. 109, p. 70-77Article in journal (Refereed)
    Abstract [en]

    Background: Young drivers with Attention Deficit Hyperactivity Disorder (ADHD) are at higher risk of road traffic injuries than their peers. Increased risk correlates with poor hazard perception skill. Few studies have investigated hazard perception training using computer technology with this group of drivers. Objectives: *Determine the presence and magnitude of the between-group.and within- subject change in hazard perception skills in young drivers with ADHD who receive Drive Smart training. *Determine whether training facilitated change in hazard perception is maintained over time. Methods: This was a feasibility study, randomised control trial conducted in Australia. The design included a delayed treatment for the control group. Twenty-five drivers with a diagnosis of ADHD were randomised to the Immediate Intervention or Delayed Intervention group.The Immediate Intervention group received a training session using a computer application entitled Drive Smart. The Delayed Intervention group watched a documentary video initially (control condition), followed by the Drive Smart computer training session. The participants hazard perception skill was measured using the Hazard Perception Test (HPT). Findings: After adjusting for baseline scores, there was a significant betweengroup difference in post-intervention HPT change scores in favour of the Immediate Intervention group. The magnitude of the effect was large. There was no significant within-group delayed intervention effect. A significant maintenance effect was found at 6 week follow-up for the Immediate Intervention group. Conclusions: The hazard perception skills of participants improved following training with large effect size and some maintenance of gain. A multimodal approach to training is indicated to facilitate maintenance. A full-scale trial is feasible.

  • 26.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Dags att folkbilda om smärta2016In: Svenska dagbladet, ISSN 1101-2412, no 10 AprilArticle in journal (Other (popular science, discussion, etc.))
  • 27.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gender differences in dispensed analgesics in Sweden during 2006-2015 - an observational, nationwide, whole-population study2018In: International Journal of Women's Health, ISSN 1179-1411, E-ISSN 1179-1411, Vol. 10, p. 55-64Article in journal (Refereed)
    Abstract [en]

    A potentially illuminating way of looking at gender differences in health and disease is to study differences in drug utilization. The aim of this study was to describe gender differences in dispensed analgesics (including nonsteroidal anti-inflammatory drugs [NSAIDs]) in Sweden during 2006-2015.

  • 28.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Genombrottssmärta2013In: BestPractice Smärta, p. 17-19Article in journal (Other academic)
  • 29.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Intrathekal smärtbehandling med zikonotid – erfarenheter från Linköping2015In: BestPractice Smärta, Vol. 10, p. 11-13Article in journal (Other academic)
  • 30.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Lättläst översikt om smärta2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, article id 112:DSUTArticle, book review (Other (popular science, discussion, etc.))
  • 31.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Långvarig smärta efter kirurgi, neuropatisk smärta, CRPS2017In: Information från Läkemedelsverket, ISSN 1101-7104, Vol. 3, p. 34-38Article in journal (Other academic)
    Abstract [sv]

    Neuropatisk smärta orsakas definitionsmässigt av en skada eller sjukdom i det somatosensoriska nervsystemet. Långvarig postoperativ smärta (LPOS) är tämligen vanligt, framför allt efter ingrepp som exempelvis amputation, torakotomi, eller mastektomi. I många fall anses LPOS vara av neuropatisk karaktär, och den farmakologiska behandlingen utgår då i stor utsträckning från rekommendationerna för behandling av neuropatisk smärta, med fokus på vissa antidepressiva läkemedel (amitriptylin, duloxetin) och gabapentinoider (gabapentin, pregabalin). Topikal behandling med till exempel lidokainplåster kan vara av stort värde när smärtan utlöses av lätt beröring av huden (allodyni). Överlag bör stor försiktighet råda angående långtidsanvändning av opioider. Vid LPOS efter bukkirurgi bör man speciellt beakta opioidernas negativa effekter på tarmfunktionen, eftersom en ”ond cirkel” kan uppkomma mellan ökade doser opioider och ökad smärta. Komplext regionalt smärtsyndrom (CRPS) kan uppkomma i en extremitet efter trauma av lindrig karaktär och/eller immobilisering (till exempel gipsning). Även om CRPS typ 1 definitionsmässigt inte är ett neuropatiskt smärttillstånd, är de farmakologiska behandlingsprinciperna ändå i stor utsträckning desamma som för neuropatisk smärta. Mer forskning behövs för att på sikt kunna få fram bättre, mer mekanism-baserade behandlingsmetoder.

  • 32.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Med diagnosen som sköld2014In: NOD, Vol. 2Article in journal (Other (popular science, discussion, etc.))
  • 33.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Nurturing the Virtues: Upholding Professionalism in the Midst of Busy Medical Practice2019In: Journal of Continuing Education in the Health Professions, ISSN 0894-1912, E-ISSN 1554-558X, Vol. 39, no 1, p. 69-72Article in journal (Refereed)
    Abstract [en]

    Tom L. Beauchamp and James F. Childress (Bamp;C) book Principles of Biomedical Ethics is well known for its fourprinciple approach to biomedical ethics. However, the authors also emphasize the importance of the virtues of health care personnel. After a short overview of virtue ethics, the five "focal virtues" described by Bamp;C are discussed and applied to a chronic pain example. The question of how virtues are learned in the health care setting is addressed, and it is argued that virtues such as the ones defended by Bamp;C are acquired when health care personnel are socialized in an environment dedicated to the continuous upholding of practices that aim at the telos of medicine. Viewed from this perspective, professional isolation can be considered to be dangerous; the upholding of medical professionalism throughout a whole career largely presupposing the existence of a community where virtues relevant to the practice of medicine are embodied and kept alive. The concept of professional socialization is important in that respect. Finally, some potential general implications of this view for continuing professional development are proposed.

  • 34.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Om smärta som glädjekälla och livsnödvändigt ont2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 38, p. 1586-87Article in journal (Other (popular science, discussion, etc.))
  • 35.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Pain as the Perception of Someone: An Analysis of the Interface Between Pain Medicine and Philosophy2019In: Health Care Analysis, ISSN 1065-3058, E-ISSN 1573-3394, Vol. 27, no 1, p. 13-25Article in journal (Refereed)
    Abstract [en]

    Based largely on the so-called problem of asymmetry in concept application, philosopher Murat Aydede has argued for a non-perceptual view of pain. Aydede is of course not denying basic neurobiological facts about neurons, action potentials, and the like, but he nonetheless makes a strong philosophical case for pain not being the perception of something extramental. In the present paper, after having stated some of the presuppositions I hold as a physician and pain researcher, and after having shortly described Aydedes critique of perceptual theories of pain, I make a constructive proposal centred around the concept of pain as the perception of some-one, not some-thing. In doing so, I propose that there often is a problematic duality at work when we think about pain, namely the mental/extramental duality. This pre-reflective mindset creates difficulties when reflecting over pain. Instead, I propose the body/world duality as being more helpful. Two neologisms, cosmoception and egoception, are presented as an alternative to the twin concepts of exteroception and interoception. It is argued that the new concepts have the advantage of not pushing our thought into a mental/extra-mental dichotomy. Hence, when in pain (which is an instance of egoception), I get epistemic access to the body that is I, to how I fare in this world. From that perspective, pain is not the perception of something, but of someone-namely, the self. In the final part of the paper, this proposal is discussed in dialogue with a paper from phenomenological thinker Jennifer Bullington.

  • 36.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Faculty of Health Sciences.
    Pain in the Blood? Envisioning Mechanism-Based Diagnoses and Biomarkers in Clinical Pain Medicine.2015In: Diagnostics, ISSN 1777-781X, Vol. 5, no 1, p. 84-95Article in journal (Refereed)
    Abstract [en]

    Chronic pain is highly prevalent, and pain medicine lacks objective biomarkers to guide diagnosis and choice of treatment. The current U.S. "opioid epidemic" is a reminder of the paucity of effective and safe treatment options. Traditional pain diagnoses according to the International Classification of Diseases are often unspecific, and analgesics are often prescribed on a trial-and-error basis. In contrast to this current state of affairs, the vision of future mechanism-based diagnoses of chronic pain conditions is presented in this non-technical paper, focusing on the need for biomarkers and the theoretical complexity of the task. Pain is and will remain a subjective experience, and as such is not objectively measurable. Therefore, the concept of "noci-marker" is presented as an alternative to "pain biomarker", the goal being to find objective, measurable correlates of the pathophysiological processes involved in different chronic pain conditions. This vision entails a call for more translational pain research in order to bridge the gap between clinical pain medicine and preclinical science.

  • 37.
    Bäckryd, Emmanuel
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    "Professional Helper" or "Helping Professional?" The Patient-Physician Relationship in the Chronic Pain Setting, With Special Reference to the Current Opioid Debate2016In: Journal of Continuing Education in the Health Professions, ISSN 0894-1912, E-ISSN 1554-558X, Vol. 36, no 2, p. 133-137Article in journal (Refereed)
    Abstract [en]

    There seems to be a strong cultural expectation among patients for effective pain relief. As a result, physicians often find themselves trying to bridge the gap between the chronic pain patients expectations and harsh biomedical reality. The typology of Emanuel and Emanuel of four models for the patient-physician relationship is used in this article as a conceptual tool to examine the possible roles of physicians in the context of chronic noncancer pain. Their typology is reconceptualized as a "pathway" along which the physician is able to walk more or less far, starting from the "information" end of the path. The other end of the pathway is "caring deliberation." I then propose that, in pain medicine today, consumerism is a powerful incentive for physicians to stay at the information end of the spectrum. Against this background, I discuss the current opioid epidemic in the United States and the need for what has been called a new medical professionalism. I conclude by challenging educators involved in pain medicine continuing professional development to not only design adequate biomedical-educational programs, but also consider issues like professionalism, personal development, critical self-reflection, and the ethics of engaging in caring deliberation with chronic pain patients.

  • 38.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Smärtan och medvetandet gäckar filosofer och forskare2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 20-21, p. 1039-40Article in journal (Other (popular science, discussion, etc.))
  • 39.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Smärtmetaforernas dolda budskap2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, article id 112:DSUTArticle in journal (Other (popular science, discussion, etc.))
  • 40.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Synliggör den osynliga smärtan2016Other (Other (popular science, discussion, etc.))
  • 41.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    The Cerebrospinal Fluid in Severe Pain Conditions: Clinical, Pharmacological and Proteomic Aspects2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The treatment of both cancer pain and non-cancer chronic pain is still suboptimal. The overall aim of this PhD thesis was to conduct translational pain research at the interface between clinical pain medicine and the field of human proteomics, using the practice of intrathecal analgesia at our institution as a starting point. Hence, the cerebrospinal fluid (CSF) is at the centre of the present dissertation, both as a target for infusing analgesics (Papers I and II – clinical and pharmacological aspects) and as an important biofluid for human biomarker studies (Papers III and IV – proteomic aspects). In Paper I, 28 cases of intrathecal analgesia in cancer patients were prospectively followed. Movement-evoked breakthrough pain remained a major clinical problem throughout the study month despite otherwise successful intrathecal analgesia (defined as good control of spontaneous resting pain paralleled by a marked decrease of concomitant systemic opioid doses). This study therefore illustrates the importance of considering not only spontaneous resting pain but also movement-evoked breakthrough pain.

    In Paper II, an expert-based algorithm for trialing the intrathecal analgesic ziconotide by bolus injections was evaluated in an open-label study of 23 patients with chronic neuropathic pain. We found few responders (13%) according to the strict criteria of the algorithm, but ziconotide bolus injection trialing seems feasible. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (with very slow tissue penetration due to high hydrophilicity) calls the rationale for ziconotide bolus trialing into question.

    In Paper III, we found low levels of beta-endorphin in the CSF of chronic neuropathic pain patients (n=15) compared to healthy controls (n=19). We speculate that this might indicate dysfunctional top-down control of nociception. Substance P levels in the CSF did not differ by univariate statistics. In Paper IV, the CSF proteome of 11 patients with chronic neuropathic pain and 11 healthy controls was exploratively studied, combining gel-based proteomics with multivariate data analysis. After eliminating four proteins associated with age, 32 proteins were found to highly discriminate between groups. Among these, the seven proteins having the highest discriminatory power between patients and controls were: one isoform of angiotensinogen, two isoforms of alpha-1-antitrypsin, three isoforms of haptoglobin, and one isoform of pigment epithelium-derived factor.

    In conclusion, this PhD thesis demonstrates the fruitfulness of studying the CSF, both as a target for infusing analgesics and as a potential mirror of the neurobiological processes involved in pathological pain conditions. The thesis points to the need for more research into the mechanisms of different pain conditions, in order to hopefully achieve the vision of mechanism-based pain diagnoses.

    List of papers
    1. Movement-evoked breakthrough cancer pain despite intrathecal analgesia: a prospective series
    Open this publication in new window or tab >>Movement-evoked breakthrough cancer pain despite intrathecal analgesia: a prospective series
    2011 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 9, p. 1139-1146Article in journal (Refereed) Published
    Abstract [en]

    Background: Intrathecal analgesia (ITA) is a valuable treatment option for intractable cancer-related pain. However, the issue of movement-evoked breakthrough pain (BTP) has not been specifically investigated in the ITA setting. The aim of the study was to evaluate the effect of ITA on spontaneous resting pain intensity (SRPI), doses of non-ITA opioids, and specifically on movement-evoked pain intensity (MEPI). less thanbrgreater than less thanbrgreater thanMethods: We prospectively studied 28 consecutive patients who graded SRPI and MEPI on a 0-10 numerical rating scale (NRS) at the time of ITA procedure, after 1 week, and after 1 month. Mild pain was defined as NRS andlt;= 3 and severe pain as NRS andgt;= 7. Concomitant doses of opioids were registered. less thanbrgreater than less thanbrgreater thanResults: After 1 week, no patient had severe SRPI compared with 31% before ITA, and the proportion of patients with mild SRPI had increased from 27% to 76%. Meanwhile, the median daily dose of non-ITA opioids decreased from 575 to 120 mg of oral morphine equivalents. The effect on SRPI and on doses of non-ITA opioids remained essentially unchanged during the study month, but the proportion of patients having severe MEPI did not change significantly: 44% still had severe MEPI after 1 week and 40% after 1 month. less thanbrgreater than less thanbrgreater thanConclusion: Movement-evoked BTP was a major clinical problem throughout the study month despite otherwise successful ITA. Improving the quality of life of patients with intractable cancer-related pain should include developing strategies to better deal with movement-evoked BTP.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-71376 (URN)10.1111/j.1399-6576.2011.02510.x (DOI)000295102500015 ()
    Available from: 2011-10-14 Created: 2011-10-14 Last updated: 2017-12-08
    2. Ziconotide Trialing by Intrathecal Bolus Injections: An Open-Label Non-Randomized Clinical Trial in Postoperative/Posttraumatic Neuropathic Pain Patients Refractory to Conventional Treatment
    Open this publication in new window or tab >>Ziconotide Trialing by Intrathecal Bolus Injections: An Open-Label Non-Randomized Clinical Trial in Postoperative/Posttraumatic Neuropathic Pain Patients Refractory to Conventional Treatment
    2015 (English)In: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 18, no 5, p. 404-413Article in journal (Refereed) Published
    Abstract [en]

    Objectives: The aim of this open-label, non-randomized, clinical trial was to evaluate the feasibility of trialing ziconotide by intrathecal bolus injections. Material and Methods: Twenty-three patients, who had peripheral neuropathic pain refractory to pharmacological treatment and were under consideration for Spinal Cord Stimulation, received up to three ziconotide bolus injections according to a comprehensive algorithm. After a first injection of 2.5g, the patients progressed in the algorithm depending on the presence or absence of pain reduction and significant adverse events. A patient was considered a "responder" if experiencing pain reduction and no significant adverse event on two consecutive occasions at the same dosage. Results: We found a low proportion of responders (13%). However 30% of patients experienced greater than= 30% pain reduction on a least one injection, yielding a number needed to treat of similar to 3 for clinically significant pain relief. Pain intensity changed significantly over time (0-6h) (p = 0.047) after a mean ziconotide dose of 2.75 mu g. Adverse events were as expected, and no serious adverse event occurred. We did not find any statistical association between response to Spinal Cord Stimulation and response to ziconotide. Conclusions: Ziconotide bolus injection trialing seems feasible, but the proportion of responders in the present study was low. Adverse events were as expected, and no serious adverse event occurred. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (slow tissue penetration due to high hydrophilicity) calls the rationale for bolus trialing into question.

    Place, publisher, year, edition, pages
    Wiley, 2015
    Keywords
    Bolus; intrathecal; spinal; trialing; ziconotide
    National Category
    Clinical Medicine Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-120352 (URN)10.1111/ner.12293 (DOI)000357388400010 ()25879804 (PubMedID)
    Note

    Funding Agencies|County Council of Ostergotland; Swedish Research Council

    Available from: 2015-07-31 Created: 2015-07-31 Last updated: 2018-01-11
    3. Do low levels of Beta-endorphin in the cerebrospinal fluid indicate defective top-down inhibition in patients with chronic neuropathic pain? A cross-sectional, comparative study
    Open this publication in new window or tab >>Do low levels of Beta-endorphin in the cerebrospinal fluid indicate defective top-down inhibition in patients with chronic neuropathic pain? A cross-sectional, comparative study
    2014 (English)In: Pain medicine (Malden, Mass.), ISSN 1526-2375, E-ISSN 1526-4637, Vol. 15, no 1, p. 111-119Article in journal (Refereed) Published
    Abstract [en]

    Objective

    Pain medicine still lacks mechanism-specific biomarkers to guide diagnosis and treatment, and defective top-down modulation is an important factor in the pathophysiology of chronic pain conditions. Using modern analytical tools and advanced multivariate statistical analysis, the aim of this study was to revisit two classical potential biomarkers of pro- and anti-nociception in humans (substance P and beta-endorphin), focusing particularly on the cerebrospinal fluid (CSF).

    Design

    Cross-sectional, comparative, observational study.

    Subjects

    Patients with chronic, post-traumatic and/or post-surgical, neuropathic pain refractory to conventional treatment (N = 15) and healthy controls (N = 19) were included.

    Methods

    Samples were taken from CSF and blood, and levels of substance P and beta-endorphin were investigated using a Luminex technology kit.

    Results

    We found low levels of beta-endorphin in the CSF of neuropathic pain patients (66 ± 11 pcg/mL) compared with healthy controls (115 ± 14 pcg/mL) (P = 0.017). Substance P levels in the CSF did not differ (20 ± 2 pcg/mL, 26 ± 2, P = 0.08). However, our multivariate data analysis showed that belonging to the patient group was associated with low levels of both substances in the CSF. A higher correlation between the levels of beta-endorphin and substance P in CSF was found in healthy controls than in patients (rs = 0.725, P < 0.001 vs rs = 0.574, P = 0.032).

    Conclusions

    Patients with chronic neuropathic pain due to trauma or surgery had low levels of beta-endorphin in the CSF. We speculate that this could indicate a defective top-down modulation of pain in chronic neuropathic pain. Our results also illustrate the importance of taking a system-wide, multivariate approach when searching for biomarkers.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2014
    Keywords
    Beta-Endorphin; Biomarker; Cerebrospinal Fluid; Neuropathic; Pain; Substance P
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-104231 (URN)10.1111/pme.12248 (DOI)000329756400011 ()
    Available from: 2014-02-12 Created: 2014-02-12 Last updated: 2017-12-06Bibliographically approved
    4. Multivariate proteomic analysis of the cerebrospinal fluid of patients with peripheral neuropathic pain and healthy controls: a hypothesis-generating pilot study
    Open this publication in new window or tab >>Multivariate proteomic analysis of the cerebrospinal fluid of patients with peripheral neuropathic pain and healthy controls: a hypothesis-generating pilot study
    Show others...
    2015 (English)In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 8, p. 321-333Article in journal (Refereed) Published
    Abstract [en]

    Pain medicine lacks objective biomarkers to guide diagnosis and treatment. Combining two-dimensional gel proteomics with multivariate data analysis by projection, we exploratively analyzed the cerebrospinal fluid of eleven patients with severe peripheral neuropathic pain due to trauma and/or surgery refractory to conventional treatment and eleven healthy controls. Using orthogonal partial least squares discriminant analysis, we identified a panel of 36 proteins highly discriminating between the two groups. Due to a possible confounding effect of age, a new model with age as outcome variable was computed for patients (n=11), and four out of 36 protein spots were excluded due to a probable influence of age. Of the 32 remaining proteins, the following seven had the highest discriminatory power between the two groups: an isoform of angiotensinogen (upregulated in patients), two isoforms of alpha-1-antitrypsin (downregulated in patients), three isoforms of haptoglobin (upregulated in patients), and one isoform of pigment epithelium-derived factor (downregulated in patients). It has recently been hypothesized that the renin–angiotensin system may play a role in the pathophysiology of neuropathic pain, and a clinical trial of an angiotensin II receptor antagonist was recently published. It is noteworthy that when searching for neuropathic pain biomarkers with a purely explorative methodology, it was indeed a renin–angiotensin system protein that had the highest discriminatory power between patients and controls in the present study. The results from this hypothesis-generating pilot study have to be confirmed in larger, hypothesis-driven studies with age-matched controls, but the present study illustrates the fruitfulness of combining proteomics with multivariate data analysis in hypothesis-generating pain biomarker studies in humans.

    Place, publisher, year, edition, pages
    Dovepress, 2015
    Keywords
    Cerebrospinal fluid, multivariate data analysis, neuropathic pain, proteomics
    National Category
    Nursing Surgery
    Identifiers
    urn:nbn:se:liu:diva-121493 (URN)10.2147/JPR.S82970 (DOI)000364718500002 ()26170714 (PubMedID)
    Note

    Funding agencies: Swedish Research Council; Swedish Council for Working Life and Social Research [2010-0913]; County Council of Ostergotland (Sinnescentrum); Halsofonden foundation

    Available from: 2015-09-22 Created: 2015-09-22 Last updated: 2017-12-05Bibliographically approved
  • 42.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    The opioid and pain intensity index-A proposal2019In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 63, no 1, p. 133-134Article in journal (Other academic)
    Abstract [en]

    n/a

  • 43.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Edström, Sofia
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Do fragments and glycosylated isoforms of alpha-1-antitrypsin in CSF mirror spinal pathophysiological mechanisms in chronic peripheral neuropathic pain? An exploratory, discovery phase study2018In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 18, article id 116Article in journal (Refereed)
    Abstract [en]

    Background: Post-translational modifications (PTMs) generate a tremendous protein diversity from the similar to 20,000 protein-coding genes of the human genome. In chronic pain conditions, exposure to pathological processes in the central nervous system could lead to disease-specific PTMs detectable in the cerebrospinal fluid (CSF). In a previous hypothesis-generating study, we reported that seven out of 260 CSF proteins highly discriminated between neuropathic pain patients and healthy controls: one isoform of angiotensinogen (AG), two isoforms of alpha-1-antitrypsin (AT), three isoforms of haptoglobin (HG), and one isoform of pigment epithelium-derived factor (PEDF). The present study had three aims: (1) To examine the multivariate inter-correlations between all identified isoforms of these seven proteins; (2) Based on the results of the first aim, to characterize PTMs in a subset of interesting proteins; (3) To regress clinical pain data using the 260 proteins as predictors, thereby testing the hypothesis that the above-mentioned seven discriminating proteins and/or the characterized isoforms/fragments of aim (2) would be among the proteins having the highest predictive power for clinical pain data. Methods: CSF samples from 11 neuropathic pain patients and 11 healthy controls were used for biochemical analysis of protein isoforms. PTM characterization was performed using enzymatic reaction assay and mass spectrometry. Multivariate data analysis (principal component analysis and orthogonal partial least square regression) was applied on the quantified protein isoforms. Results: We identified 5 isoforms of AG, 18 isoforms of AT, 5 isoforms of HG, and 5 isoforms of PEDF. Fragments and glycosylated isoforms of AT were studied in depth. When regressing the pain intensity data of patients, three isoforms of AT, two isoforms of PEDF, and one isoform of angiotensinogen "reappeared" as major results, i.e., they were major findings both when comparing patients with healthy controls and when regressing pain intensity in patients. Conclusions: Altered levels of fragments and/or glycosylated isoforms of alpha-1-antitrypsin might mirror pathophysiological processes in the spinal cord of neuropathic pain patients. In particular, we suggest that a putative disease-specific combination of the levels of two different N-truncated fragments of alpha-1-antitrypsin might be interesting for future CSF and/or plasma biomarker investigations in chronic neuropathic pain.

  • 44.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Carlsson, Anders K
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Multivariate proteomic analysis of the cerebrospinal fluid of patients with peripheral neuropathic pain and healthy controls: a hypothesis-generating pilot study2015In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 8, p. 321-333Article in journal (Refereed)
    Abstract [en]

    Pain medicine lacks objective biomarkers to guide diagnosis and treatment. Combining two-dimensional gel proteomics with multivariate data analysis by projection, we exploratively analyzed the cerebrospinal fluid of eleven patients with severe peripheral neuropathic pain due to trauma and/or surgery refractory to conventional treatment and eleven healthy controls. Using orthogonal partial least squares discriminant analysis, we identified a panel of 36 proteins highly discriminating between the two groups. Due to a possible confounding effect of age, a new model with age as outcome variable was computed for patients (n=11), and four out of 36 protein spots were excluded due to a probable influence of age. Of the 32 remaining proteins, the following seven had the highest discriminatory power between the two groups: an isoform of angiotensinogen (upregulated in patients), two isoforms of alpha-1-antitrypsin (downregulated in patients), three isoforms of haptoglobin (upregulated in patients), and one isoform of pigment epithelium-derived factor (downregulated in patients). It has recently been hypothesized that the renin–angiotensin system may play a role in the pathophysiology of neuropathic pain, and a clinical trial of an angiotensin II receptor antagonist was recently published. It is noteworthy that when searching for neuropathic pain biomarkers with a purely explorative methodology, it was indeed a renin–angiotensin system protein that had the highest discriminatory power between patients and controls in the present study. The results from this hypothesis-generating pilot study have to be confirmed in larger, hypothesis-driven studies with age-matched controls, but the present study illustrates the fruitfulness of combining proteomics with multivariate data analysis in hypothesis-generating pain biomarker studies in humans.

  • 45.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Plasma pro-inflammatory markers in chronic neuropathic pain: A multivariate, comparative, cross-sectional pilot study2016In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, no 10, p. 1-5Article in journal (Refereed)
    Abstract [en]

    Background: Caused by a lesion or disease of the somatosensory system, neuropathic pain is notoriously difficult to treat with conventional analgesics. It has been suggested that inflammatory cytokines play a role in the development and maintenance of neuropathic pain. But human studies of these substances are relatively few and partly contradictory. Objectives: To simultaneously investigate the plasma levels of chemokine interleukin 8 (IL-8) and the cytokines IL-6, IL-1, and Granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with peripheral neuropathic pain (most of whom due to failed back surgery syndrome) (n = 14) compared to controls (n = 17). Results: IL-6 was significantly higher in patients than in controls (0.92 ± 0.12 pg/ml vs. 0.57 ± 0.08 pg/ml, p = 0.012). IL-1, IL-8, and GM-CSF levels did not differ between the two groups. A multivariate analysis showed a tendency for patients also to have higher GM-CSF plasma levels than controls. Conclusions: This study found an increased level of IL-6 in plasma in patients with neuropathic pain, but not for the other pro-inflammatory substances investigated. There are several possible confounders not registered or controlled for in this and other studies of neuropathic pain. Implications: Larger studies that take several possible confounders into consideration are needed to further investigate the levels of plasma cytokines in different pain conditions. © 2015 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  • 46.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Hoffmann, Mikael
    Stiftelsen NEPI - nätverk för läkmedelsepidemiologi - Linköping, Sweden .
    Dynamiken i förskrivningen av opioider i Sverige 2000–2015 - Markanta omfördelningar inom opioidgruppen, men ingen »epidemi«2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Article in journal (Refereed)
    Abstract [en]

    Opioid prescription changes in Sweden 2000-2015 In contrast to the well-established »opioid epidemic« in the US, very little is known about how the prescription of opioids in Sweden has developed during the last decade. Aggregated data from the open Statistical database of the Swedish Board of Health and Welfare were analyzed descriptively. The yearly prevalence of opioid prescription did not change 2006-2015, but there were dramatic shifts in the choice of opioids. During this period, dextropropoxyphene was pulled off the market. Tramadol was used by fewer individuals (-54 % over the decade), but dosages expressed as Defined Daily Dose/patient/year (DDD/pat/y) increased (+41 %). In contrast, oxycodone and morphine were used by more individuals (+465 % and +137 %, respectively), but DDD/pat/y decreased during the period (-56% and -54%). Studies on non-aggregated data from available registries are needed to further elucidate the circumstances and possible consequences of these shifts in opioid prescription patterns.

  • 47.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Lind, Anne-Li
    Uppsala University, Sweden.
    Thulin, Mans
    Uppsala University, Sweden.
    Larsson, Anders
    Uppsala University, Sweden.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gordh, Torsten
    Uppsala University, Sweden.
    High levels of cerebrospinal fluid chemokines point to the presence of neuroinflammation in peripheral neuropathic pain: a cross-sectional study of 2 cohorts of patients compared with healthy controls2017In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 158, no 12, p. 2487-2495Article in journal (Refereed)
    Abstract [en]

    Animal models suggest that chemokines are important mediators in the pathophysiology of neuropathic pain. Indeed, these substances have been called "gliotransmitters," a term that illustrates the close interplay between glial cells and neurons in the context of neuroinflammation and pain. However, evidence in humans is scarce. The aim of the study was to determine a comprehensive cerebrospinal fluid (CSF) inflammatory profile of patients with neuropathic pain. Our hypothesis was that we would thereby find indications of a postulated on-going process of central neuroinflammation. Samples of CSF were collected from 2 cohorts of patients with neuropathic pain (n = 11 and n = 16, respectively) and healthy control subjects (n 5 11). The samples were analyzed with a multiplex proximity extension assay in which 92 inflammation-related proteins were measured simultaneously (Proseek Multiplex Inflammation I; Olink Bioscience, Uppsala, Sweden). Univariate testing with control of false discovery rate, as well as orthogonal partial least squares discriminant analysis, were used for statistical analyses. Levels of chemokines CXCL6, CXCL10, CCL8, CCL11, CCL23 in CSF, as well as protein LAPTGF-beta-1, were significantly higher in both neuropathic pain cohorts compared with healthy controls, pointing to neuroinflammation in patients. These 6 proteins were also major results in a recent similar study in patients with fibromyalgia. The findings need to be confirmed in larger cohorts, and the question of causality remains to be settled. Because it has been suggested that prevalent comorbidities to chronic pain (eg, depression, anxiety, poor sleep, and tiredness) also are associated with neuroinflammation, it will be important to determine whether neuroinflammation is a common mediator.

  • 48.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Persson, Elisabeth B.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Larsson, Annelie Inghilesi
    Qual Stat AB, Sweden.
    Fischer, Marcelo Rivano
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Chronic pain patients can be classified into four groups: Clustering-based discriminant analysis of psychometric data from 4665 patients referred to a multidisciplinary pain centre (a SQRP study)2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192623Article in journal (Refereed)
    Abstract [en]

    Objective To subgroup chronic pain patients using psychometric data and regress the variables most responsible for subgroup discrimination. Design Cross-sectional, registry-based study. Setting and subjects Chronic pain patients assessed at a multidisciplinary pain centre between 2008 and 2015. Methods Data from the Swedish quality registry for pain rehabilitation (SQRP) were retrieved and analysed by principal component analysis, hierarchical clustering analysis, and partial least squares-discriminant analysis. Results Four subgroups were identified. Group 1 was characterized by low "psychological strain", the best relative situation concerning pain characteristics (intensity and spreading), the lowest frequency of fibromyalgia, as well as by a slightly older age. Group 2 was characterized by high "psychological strain" and by the most negative situation with respect to pain characteristics (intensity and spreading). Group 3 was characterized by high "social distress", the longest pain durations, and a statistically higher frequency of females. The frequency of three neuropathic pain conditions was generally lower in this group. Group 4 was characterized by high psychological strain, low "social distress", and high pain intensity. Conclusions The identification of these four clusters of chronic pain patients could be useful for the development of personalized rehabilitation programs. For example, the identification of a subgroup characterized mainly by high perceived "social distress" raises the question of how to best design interventions for such patients. Differentiating between clinically important subgroups and comparing how these subgroups respond to interventions is arguably an important area for further research.

  • 49.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    Sörensen, Jan
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ziconotide Trialing by Intrathecal Bolus Injections: An Open-Label Non-Randomized Clinical Trial in Postoperative/Posttraumatic Neuropathic Pain Patients Refractory to Conventional Treatment2015In: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 18, no 5, p. 404-413Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this open-label, non-randomized, clinical trial was to evaluate the feasibility of trialing ziconotide by intrathecal bolus injections. Material and Methods: Twenty-three patients, who had peripheral neuropathic pain refractory to pharmacological treatment and were under consideration for Spinal Cord Stimulation, received up to three ziconotide bolus injections according to a comprehensive algorithm. After a first injection of 2.5g, the patients progressed in the algorithm depending on the presence or absence of pain reduction and significant adverse events. A patient was considered a "responder" if experiencing pain reduction and no significant adverse event on two consecutive occasions at the same dosage. Results: We found a low proportion of responders (13%). However 30% of patients experienced greater than= 30% pain reduction on a least one injection, yielding a number needed to treat of similar to 3 for clinically significant pain relief. Pain intensity changed significantly over time (0-6h) (p = 0.047) after a mean ziconotide dose of 2.75 mu g. Adverse events were as expected, and no serious adverse event occurred. We did not find any statistical association between response to Spinal Cord Stimulation and response to ziconotide. Conclusions: Ziconotide bolus injection trialing seems feasible, but the proportion of responders in the present study was low. Adverse events were as expected, and no serious adverse event occurred. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (slow tissue penetration due to high hydrophilicity) calls the rationale for bolus trialing into question.

  • 50.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Tanum, Lars
    Akershus University Hospital, Norway.
    Lind, Anne-Li
    Uppsala University, Sweden.
    Larsson, Anders
    Uppsala University, Sweden.
    Gordh, Torsten
    Uppsala University, Sweden.
    Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma2017In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 10Article in journal (Refereed)
    Abstract [en]

    In addition to central hyperexcitability and impaired top-down modulation, chronic inflammation probably plays a role in the pathophysiology of fibromyalgia (FM). Indeed, on the basis of both animal experiments and human studies involving the analysis of cytokines and other inflammation-related proteins in different body fluids, neuroinflammatory mechanisms are considered to be central to the pathophysiology of many chronic pain conditions. However, concerning FM, previous human plasma/serum and/or cerebrospinal fluid (CSF) cytokine studies have looked only at a few predetermined cytokine candidates. Instead of analyzing only a few substances at a time, we used a new multiplex protein panel enabling simultaneous analysis of 92 inflammation-related proteins. Hence, we investigated the CSF and plasma inflammatory profiles of 40 FM patients compared with CSF from healthy controls (n= 10) and plasma from blood donor controls (n= 46). Using multivariate data analysis by projection, we found evidence of both neuroinflammation (as assessed in CSF) and chronic systemic inflammation (as assessed in plasma). Two groups of proteins (one for CSF and one for plasma) highly discriminating between patients and controls are presented. Notably, we found high levels of CSF chemokine CX3CL1 (also known as fractalkine). In addition, previous findings concerning IL-8 in FM were replicated, in both CSF and plasma. This is the first time that such an extensive inflammatory profile has been described for FM patients. Hence, FM seems to be characterized by objective biochemical alterations, and the lingering characterization of its mechanisms as essentially idiopathic or even psychogenic should be seen as definitively outdated.

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