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  • 1.
    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.))
  • 2.
    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.

  • 3.
    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)
  • 4.
    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)
  • 5.
    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.))
  • 6.
    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.

  • 7.
    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.))
  • 8.
    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.

  • 9.
    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.))
  • 10.
    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.

  • 11.
    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.

  • 12.
    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.

  • 13.
    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.))
  • 14.
    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.))
  • 15.
    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.))
  • 16.
    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
  • 17.
    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

  • 18.
    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.

  • 19.
    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.

  • 20.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, 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 Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Pain and Rehabilitation Centre.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    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 study2014In: Pain medicine (Malden, Mass.), ISSN 1526-2375, E-ISSN 1526-4637, Vol. 15, no 1, p. 111-119Article in journal (Refereed)
    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.

  • 21.
    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.

  • 22.
    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.

  • 23.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Larsson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Habilitation in Central County.
    Movement-evoked breakthrough cancer pain despite intrathecal analgesia: a prospective series2011In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 9, p. 1139-1146Article in journal (Refereed)
    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.

  • 24.
    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.

  • 25.
    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.

  • 26.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Sörensen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Gerdle, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Nerve block as analgesia forneoplastic brachial plexopathy2010In: European Journal of Palliative Care, ISSN 1352-2779, E-ISSN 1479-0793, Vol. 17, no 5, p. 218-220Article in journal (Other academic)
    Abstract [en]

    Brachial plexus nerve blocks are performed to treat patients with chronic pain referable to the brachial plexus. The needle insertion and trajectory are based on palpation of surface landmarks. Occasionally, the surface landmarks are difficult to identify owing to body habitus or anatomic alterations secondary to surgery or radiation therapy. The intent of this manuscript is to describe a technique for brachial plexus block guided with computed tomography and to report our initial results for regional pain management.

  • 27.
    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.

  • 28.
    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.

  • 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.
    Do the potential benefits outweigh the risks? An update on the use of ziconotide in clinical practice2018In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 22, no 7, p. 1193-1202Article, review/survey (Refereed)
    Abstract [en]

    Ziconotide is a selective and potent blocker of N-type voltage-gated calcium channels. It was approved by the Food and Drug Administration in 2004 and by the European Medicines Agency in 2005 for the treatment of severe chronic pain in patients needing intrathecal analgesia (ITA). The aim of this paper is to provide a practitioner-oriented, educational, narrative, up-to-date review on the use of ziconotide in clinical pain medicine. Of special concern regarding safety is the partial incongruity between dosing statements in the Summary ofProduct Characteristics and novel low-dosage, slow uptitration recommendations. Even though ziconotide has obvious advantages compared to opioids, pain practitioners pondering the use of ziconotide nonetheless have to balance its proved potential analgesic effect against its neurological side effects, with special consideration being given to dosing and neuropsychiatric dangers. Using a seesaw analogy, the paper discusses what factors pain physicians should weigh in when considering ziconotide as ITA drug, the non-opioid advantages of ziconotide being counterbalanced by its potential psychiatric side effects. Ziconotide is an important part of the armamentarium of modern interventional pain medicine. If ITA is deemed necessary, ziconotide is a rational alternative, at least in chronic (neuropathic) non-cancer pain. However, in many European countries, ziconotide treatment is only available in a few (if any) centres. The safety profile of ziconotide is not fundamentally more worrying than that of opioids or cannabinoids; it is just different. This paper provides a concise, up-to-date and clinically-oriented summary of the use of ziconotide in clinical practice, not least concerning safety and dosage issues.

  • 30.
    Gerdle, Björn
    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.
    Ghafouri, Nazdar
    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.
    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.
    Gordh, Torsten
    Uppsala University, Sweden.
    Signs of ongoing inflammation in female patients with chronic widespread pain A multivariate, explorative, cross-sectional study of blood samples2017In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 9, article id e6130Article in journal (Refereed)
    Abstract [en]

    This cross-sectional study investigates the plasma inflammatory profile of chronic widespread pain CWP) patients compared to healthy controls CON). Rather than analyzing a relatively few substances at a time, we used a new multiplex proximity extension assay PEA) panel that enabled the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines. Seventeen women with CWP and 21 female CON participated and a venous blood sample was drawn from all subjects. Pain intensity and pain thresholds for pressure, heat, and cold were registered. A PEA panel 92 proteins) was used to analyze the blood samples. Multivariate data analysis by projection was used in the statistical analyses. Eleven proteins significantly differentiated the CON and CWP subjects R-2=0.58, Q(2)=0.37, analysis of variance of cross-validated predictive residuals P=0.006). It was not possible to significantly regress pain thresholds within each group CON or CWP). Positive significant correlations existed between several proteins and pain intensities in CWP, but the model reliability of the regression was poor. CWP was associated with systemic low-grade inflammation. Larger studies are needed to confirm the results and to investigate which alterations are condition-specific and which are common across chronic pain conditions. The presence of inflammation could promote the spreading of pain, a hallmark sign of CWP. As it has been suggested that prevalent comorbidities to pain (e.g., depression and anxiety, poor sleep, and tiredness) also are associated with inflammation, it will be important to determine whether inflammation may be a common mediator.

  • 31.
    Ghafouri, Bijar
    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. PAINOMICS Lab, Linkoping, Sweden.
    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.
    Proteomics in chronic pain; investigating mechanistic markers of pain2019In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 190, p. III-IIIArticle in journal (Other academic)
    Abstract [en]

    n/a

  • 32.
    Johansson, Joakim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Granerus, Göran
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Urinary excretion of histamine and methylhistamine after burns2012In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 38, no 7, p. 1005-1009Article in journal (Refereed)
    Abstract [en]

    Background: The increased vascular permeability seen after burn contribute to morbidity and mortality as it interferes with organ function and the healing process. Large efforts have been made to explore underlying pathophysiological mechanisms that generate increased vascular permeability after burns. Many different substances have been proposed as mediators of which histamine, serotonin and oxygen radicals are claimed most important. However, no specific blocker has convincingly been shown to be clinically effective. Early work has claimed increased histamine plasma-concentrations in humans after burn and data from animal models pointed at histamine as an important mediator. Modern human clinical studies investigating the role of histamine as a mediator of the generalized post burn increase in vascular permeability are lacking. less thanbrgreater than less thanbrgreater thanMethod: We examined histamine turnover by measuring the urinary excretion of histamine and methyl histamine for 48 h after burns in 8 patients (mean total burn surface area 24%). less thanbrgreater than less thanbrgreater thanResults: Over time, in this time frame and compared to healthy controls we found a small increase in the excretion of histamine, but no increase of its metabolite methylhistamine. less thanbrgreater than less thanbrgreater thanConclusion: Our findings do not support that histamine is an important mediator of the increased systemic vascular permeability seen after burn.

  • 33.
    Kallman, Thomas F.
    et al.
    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 Medicine and Health Sciences.
    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.
    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.
    Salivary beta-endorphin and substance P are not biomarkers of neuropathic chronic pain propensity2018In: Heliyon, ISSN 2405-8440, Vol. 4, no 8, article id e00718Article in journal (Refereed)
    Abstract [en]

    Objective

    The pathophysiology of chronic pain is complex, with most of our knowledge being derived from preclinical studies. The search for biomarkers mirroring the pathophysiology of chronic pain is ongoing, and there is an increasing interest in saliva as a diagnostic tool. Given what is known about salivary substance Pand salivary gland innervation, we hypothesized that salivary substance P and/or beta-endorphin might reflect the basal activity of these neuropeptides in the central nervous system, thereby perhaps mirroring a general propensity to chronic pain. Based on this overall hypothesis, our aim was to compare salivary levels of these neuropeptides in chronic neuropathic pain patients with healthy controls. An additional aim was to relate salivary levels to plasma levels.

    Materials and methods

    We compared salivary concentrations of beta-endorphin and substance P in 14 chronic neuropathic pain patients with concentrations in 18 healthy controls using a Luminex technology kit. Salivary-to-plasma quotients were also calculated.

    Results

    We found no significant difference between the groups' salivary concentrations of substance P and beta-endorphin. No correlation was found between salivary and plasma concentrations of each neuropeptide, which we hypothesize might point to local production of beta-endorphin and/or substance P in the salivary glands. Given high substance P salivary-to-plasma quotients, such a local production seems more likely for substance P than for beta-endorphin.

    Conclusions

    Propensity to neuropathic chronic pain was not substantiated by our analysis of salivary levels of substance P and/or beta-endorphin. However, we report salivary-to-plasma quotients that give potentially important physiological insight about these neuropeptides.

  • 34.
    Karlsson, Linn
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of 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.
    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.
    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.
    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.
    Ghafouri, Nazdar
    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.
    Intramuscular pain modulatory substances before and after exercise in women with chronic neck pain2015In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 19, no 8, p. 1075-1085Article in journal (Refereed)
    Abstract [en]

    BackgroundIn peripheral tissue, several substances influence pain and pain modulation. Exercise has been found to decrease pain and improve function for chronic pain conditions, but how and why exercise produces beneficial effects remains unclear. This study investigates whether aspects of pain and concentrations of substances with algesic, analgesic and metabolic functions differ between women with chronic neck shoulder pain (CNSP) and healthy women (CON) and whether changes are found after an exercise intervention for CNSP. MethodsForty-one women with CNSP and 24 CON subjects were included. The participants attended two microdialysis sessions with 4-6 months between the experiments. During this period, the CNSP subjects underwent an exercise intervention. Expression levels of substance P, beta-endorphin, cortisol, glutamate, lactate and pyruvate as well as pain intensity and pressure pain thresholds were analysed. ResultsAt baseline, higher concentrations of glutamate and beta-endorphin and lower concentrations of cortisol in CNSP than CON were found. After exercise, decreased levels of substance P and possibly of glutamate, increased levels of beta-endorphin and cortisol as well as decreased pain intensity and increased pain pressure thresholds were found for CNSP. ConclusionsThe findings at baseline indicated algesic and analgesic alterations in the painful trapezius muscles. The findings for CNSP after the exercise intervention, with changes in peripheral substances and decreased pain intensity and sensitivity, could reflect a long-term physiological effect of the exercise.

  • 35.
    Olausson, Patrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    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.
    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.
    Clear differences in cerebrospinal fluid proteome between women with chronic widespread pain and healthy women - a multivariate explorative cross-sectional study2017In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 10, p. 575-590Article in journal (Refereed)
    Abstract [en]

    Introduction: Frequent chronic local pain can develop into chronic widespread pain (CWP). The spread of pain is correlated with pain intensity, anxiety, and depression, conditions that ultimately lead to a poor quality of life. Knowledge is incomplete about CWPs etiology, although it has been suggested that both central hyperexcitability and/or a combination with peripheral factors may be involved. Cerebrospinal fluid (CSF) could act as a mirror for the central nervous system as proteins are signal substances that activate the formation of algesics and control nociceptive processes. To this end, this study investigates the CSF protein expression in women with CWP and in female healthy controls. Materials and methods: This study included 12 female patients with CWP diagnosed according to the American College of Rheumatology criteria with 13 healthy age-and sex-matched pain-free subjects. All subjects went through a clinical examination and answered a health questionnaire that registered sociodemographic and anthropometric data, pain characteristics, psychological status, and quality of life rating. CSF was collected by lumbar puncture from each subject. Two-dimensional gel electrophoresis in combination with mass spectrometry was used to analyze the CSF proteome. This study identifies proteins that significantly discriminate between the two groups using multivariate data analysis (MVDA) (i.e., orthogonal partial least squares discriminant analysis [OPLS-DA]). Results: There were no clinically significant levels of psychological distress and catastrophization presented in subjects with CWP. MVDA revealed a highly significant OPLS-DA model where 48 proteins from CSF explained 91% (R-2) of the variation and with a prediction of 90% (Q(2)). The highest discriminating proteins were metabolic, transport, stress, and inflammatory. Conclusion: The highest discriminating proteins (11 proteins), according to the literature, are involved in apoptotic regulations, anti-inflammatory and anti-oxidative processes, the immune system, and endogenous repair. The results of this explorative study may indicate the presence of neuro-inflammation in the central nervous system of CWP patients. Future studies should be larger and control for confounders and determine which alterations are unspecific/general and which are specific changes.

  • 36.
    Stålnacke, Britt-Marie
    et al.
    Institutionen för samhällsmedicin och rehabilitering, Umeå universitet.
    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.
    Roeck Hansen, Elisabeth
    Rehabiliteringsmedicinska Universitetskliniken Stockholm, Danderyds Sjukhus AB.
    Novo, Mehmed
    Institutionen för samhällsmedicin och rehabilitering, Umeå universitet.
    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.
    Smärtanalys och diagnossättning vid kroniska smärtor inom specialiserad smärtvård2014Report (Other academic)
    Abstract [sv]

    Vi har som modifiering av SoS diagnosriktlinje föreslagit att smärtdiagnostiken ska använda två system parallellt d.v.s. både ICD10 systemet som det föreslagits av Socialstyrelsen för den specialiserade smärtvården (exklusiveR52.2A-C och F45.4) (Bilaga 1) och en utvidgad smärtmekanistisk klassificering. Vid tillämpningen av det förra används lämpligen den lathund som har utarbetats av diagnosgruppen inom NRS (Bilaga 2). För den senare används kategorierna definierade i detta dokument (dvs. neuropatisk, nociceptiv, generaliserad, psykogen och/eller idiopatisk) tillsammans med ställningstagande till smärtkänslighet.

    Härigenom skapas mer enhetlig diagnossättning vilket är en förutsättning för kliniska riktlinjer, kliniska jämförelser och intensifierad forskning involverande diagnosaspekter.

1 - 36 of 36
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