Opioids are an essential category of medicines, and opiophobia should therefore be shunned. However, it is also important to avoid opiocentrism, i.e., the phenomenon of giving an unduly central place to opioids in the practice of pain medicine. To find a way between these two extremes, it is essential to do a thorough pain assessment and a risk analysis. In this paper, the question of how to best prescribe opioids is related to a "Pain Analysis 3×3" framework in which 3 areas, each consisting of 3 points, are discussed: 1) Is the pain acute, chronic, or cancer-related? 2) Is the pain nociceptive, neuropathic, or nociplastic? 3) Have biological, psychological and social/contextual aspects been taken into consideration (the bio-psycho-social model of pain)? Chronic nociplastic pain conditions such as e.g. fibromyalgia, irritable bowel syndrome or "unspecific" back pain are generally unsuitable for treatment with opioids.

Background: When theoretically discussing pain, the distinction between acute and chronic pain is not always taken into considera-tion. By contrast, informed by the pain medicine distinction between acute and chronic pain, the present theoretical paper analyses the phenomena of chronicity and chronification in the pain setting. Methods: Philosopher Fredrik Svenaeus and his paper The phenomenology of chronic pain: embodiment and alienation (Continental Philosophy Review 2015;48:107-122) is used as a dialogue partner.Results: Three aspects, relevant for clinicians, are discussed: (1) the distinction between emotion and mood, arguing that the process of chronification entails pain evolving from the former to the latter; (2) chronification as a process in which the pain patient becomes aware of his/her temporality, both the past and the future coming to the fore (as opposed to severe acute pain in which only the present counts, ie, getting rid of the pain now); (3) the acquisition of a pain-related narrative identity, interdisciplinary pain rehabilitation programs being described as helping patients regain a narrative identity that is not dominated by pain or by a fruitless chase after pain relief.Conclusion: Chronic pain reminds us of our temporality and of the narrative character of our lives.

Leadership issues seem to be strangely absent from discussions about what good doctoral supervision is. The purpose of this paper is to explore the concept of doctoral supervision as a form of leadership, with special reference to the university hospital setting. From a personal reflective practice point of view, James Kouzes and Barry Posner's The Five Practices of Exemplary Leadership® Model is used as a lens through which Anne Lee’s concepts of doctoral research supervision are viewed. Four out of five of Lee’s concepts seem to be leadership-related, when viewed from the perspective of Kouzes & Posner, namely “enculturation”, “critical thinking”, “emancipation”, and “relationship development”. The fifth concept, “functional”, can instead be viewed to reflect managerial skills. Hence, it seems meaningful to view doctoral supervision as a form of leadership. The present concept paper should be viewed as hypothesis-generating, and future studies should examine the proposed hypothesis in a more in-depth fashion, using appropriate empirical methodologies and not as in the present paper mere practice-based reflections.

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.

In this paper, the question of theodicy is viewed from the perspective of time. It is argued that even a very shallow analysis reveals that the concept of "long time" is deeply anthropocentric. We do not know what time is to God, but it seems that the only reason why we call billions of years a long period is because we use ourselves as measuring rods. What if the time questions we ask in this context say more about our temporal smallness than about reality itself? Three possible objections are answered: 1) It is acknowledged that this is of course not meant to be a definite answer to the problem of evil. It is merely offered as a reframing that seems strangely absent from the discussion. 2) The question of pastoral relevance is briefly discussed. 3) The troubling problem of why God created sequentially over time and not "instantaneously" is explored. It is concluded that perhaps our appraisal of time might not be ontologically valid at all. This does not make suffering easy to bear, but perhaps thoughts like these can provide a little hope and endurance-at least for those of us who are philosophically and theologically inclined.

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.

Pain is a symptom that can be associated with dangerous diseases such as cancer. Hence, to avoid delay in diagnosis of an underlying serious condition, it is important to be thorough when assessing pain. However, all pains are not symptoms of an underlying disease. Instead, many chronic pain conditions can be viewed as diseases in their own right. Indeed, sometimes the pain is the disease - such is for instance the case for fibromyalgia, painless fibromyalgia being a contradiction in terms. The new classification of chronic pain conditions according to the eleventh version of International Classification of Diseases (ICD-11) is presented and discussed. It is argued that the classification makes pain medicine visible as an academic discipline; that it may contribute to a legitimization process in which the suffering of pain patients is recognized semantically and taxonomically; and that it opens up new research possibilities in the chronic pain field.

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.

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.

Objectives: To give an overview of central aspects of pain medicine-specific clinical reasoning when assessing a pain patient. Clinical reasoning is the thinking and decision-making processes associated with clinical practice.Methods: Three core pain assessment areas that are crucial for clinical reasoning in the field of pain medicine are discussed, each of them consisting of three points.Results: First, it is important to distinguish acute, chronic non-cancer, and cancer-related pain conditions. This classical and very simple trichotomy still has important implications treatment-wise, e.g., concerning the use of opioids. Second, the pain mechanism needs to be assessed. Is the pain nociceptive, neuropathic, or nociplastic? Simply put, nociceptive pain has to do with injury of non-neural tissue, neuropathic pain is caused by a disease or lesion of the somatosensory nervous system, and nociplastic pain is believed to be related to a sensitized nervous system (c.f. the concept of "central sensitization "). This also has implications concerning treatment. Some chronic pain conditions are nowadays viewed more as diseases rather than the pain being merely a symptom. In the new ICD-11 pain classification, this is conceptualized by the characterization of some chronic pains as "primary ". Third, in addition to a conventional biomedical evaluation, psychosocial and behavioral aspects must also be assessed, the pain patient being viewed as an active agent and not merely as the passive recipient of an intervention. Hence, the importance of a dynamic bio-psycho-social perspective. The dynamic interplay of biological, psychological, and social aspects must be taken into account, putative behavioral "vicious circles " thereby being identified. Some core psycho-social concepts in pain medicine are mentioned.Conclusions: The clinical applicability and clinical reasoning power of the 3 x 3 framework is illustrated by three short (albeit fictional) case descriptions.

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.

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.

Introduction Traditionally, cancer pain has often been viewed as an independent third major category in pain medicine alongside acute pain and chronic non-cancer pain. However, the new chronic pain category MG30 in the eleventh version of International Classification of Diseases (ICD-11) includes cancer-related pain as one of its seven subgroups. In light of this, the aim of the paper is to investigate whether the traditional trichotomy should be replaced by a dichotomy between acute pain and chronic pain, cancer-related pain being part of both groups depending on the duration of pain.Methods The rationale for viewing cancer pain as a separate category is reviewed.Results Cancer being a deadly disease, cancer pain has a life-and-death and existential dimension that is different from non-cancer pain. It seems sensible to believe that this is an additional dimension to the suffering caused by cancer pain, and that clinicians should therefore take this existential dimension into consideration when assessing pain.Conclusion Without challenging the place of chronic cancer-related pain under the MG30 heading, it is concluded that while using ICD-11 in the future, pain clinicians should continue being mindful of the fact that the reality of death shapes the experience of cancer pain. The traditional trichotomy is therefore still valid and mirrors the fact that human beings are vulnerable (acute pain), temporal (chronic pain) and mortal (cancer pain).

BackgroundIn a previous paper in Philos Ethics Humanit Med, the 1937 Swedish novel Somnlos (Swedish for sleepless) by Vilhelm Moberg was used as background for a thought experiment, in which last centurys progresses concerning the safety of sleeping pills were projected into the future. This gave rise to a theoretical discussion about broad medico-philosophical questions such as (among other things) the concept of pharmaceuticalisation.MethodsIn this follow-up paper, the theme of insomnia in Somnlos is complemented by a discussion of the concept of nostalgia. The core of the paper is a theoretical discussion about the benefits and risks of nostalgia, bringing together some aspects of recent psychological research about the construct of nostalgia with the main story line of the novel.Results and ConclusionNostalgia is portrayed as being, in some sense at least, ultimately beneficial for the protagonist of Somnlos. This is congruent with recent psychological research. However, the story also shows that nostalgia may lead to problematic behaviours, at least when viewed from a virtue ethics perspective. Hence, nostalgia is both what leads the protagonist into ethically problematic behaviour and that which (paradoxically) ultimately saves him from his initial lack of courage, justice, temperance and practical wisdom. Moreover, the protagonist does not only "grow" ethically but also existentially. Hence, the novel opens up the possibility that insomnia and nostalgia might be viewed as bearers of important existential information (cf. sociologist of religion Peter L. Berger and his concept of "signals of transcendence").

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.

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Background The safety of sleeping pills has increased dramatically during the last 100 years, from barbiturates to bensodiazepines to modern day so-called Z-drugs. Methods The circumstances of prescribing sleeping pills in the early 20(th) century are illustrated by summarizing the main storyline of a novel by Swedish writer Vilhelm Moberg. This is followed by a thought experiment and a theoretical discussion. Results In his 1937 novel Somnlos (Swedish for sleepless) Vilhelm Moberg portrayed existential and relational distress in relation to insomnia. In a thought experiment, past progresses in sleeping pills safety are projected into the future. Thereby, it is claimed that important issues in the area of philosophy of medicine come to the fore. This leads to a theoretical discussion about broader questions concerning the role of the physician, the goals of medicine (as described by Lennart Nordenfelt), the concept of pharmaceuticalisation (as described notably by sociologist of sleep Simon J. Williams and co-workers), and health enhancement (c.f. Carl Elliott and the alleged wish to be better than well). Conclusion Insomnia is a prism through which important philosophical and sociological questions related to the practice of medicine can be asked.

Depression and anxiety are highly prevalent in chronic pain. Clinicians often interpret depression/anxiety as consequences of chronic pain, but some psychiatrists contend that the consequence hypothesis is overrated and that psychiatric symptoms in pain patients should be understood as part of the psychiatric disease. In this overview, the potential bidirectional nature of the relationship between chronic pain and depression/anxiety is discussed on a conceptual level. Two additional possible ways of understanding the relationship are presented: psychological vulnerability can be a risk factor for the chronification of pain, and an underlying mild chronic pain can be exacerbated when the patient encounters a new psychosocial stressor. In clinical practice, it is important not to get stuck in a fruitless chase for a causal understanding. However, it is of great value for clinicians to reflect upon the complexity and dynamic nature of the relationship between pain and depression/anxiety.

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.

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.

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 (r_s = 0.725, P < 0.001 vs r_s = 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.

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.

Objective: Rehabilitation interventions for chronic pain typically include education, cognitive behavioural therapy, and exercise therapy, or a combination of these. A systematic review and meta-analysis of rehabilitation interventions for neuropathic pain was conducted. Design: Randomized controlled trials were identified in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and PsycINFO databases from inception up to 3 March 2022. Subjects/Patients: Adults with chronic (&gt; 3 months) neuropathic pain. Methods: Primary outcomes were pain intensity, pain-related disability, and work participation. Secondary outcomes were quality of life, emotional strain, insomnia, and adverse outcomes, according to VAPAIN guidelines. Analyses were made post- intervention, which was defined as the assessment point immediately following the intervention or at the first-time measurement conducted after the intervention period. Results: In total, 15 studies (total population, n = 764) were incorporated. Most common interventions were cognitive behavioural programmes including acceptance and commitment therapy (n=4), n =4), mindfulness-based interventions (n n = 5), and yoga (n n = 2). Psychological interventions reduced both pain intensity (SMD -0.49, 95% CI -0.88 to -0.10) and pain-related disability (SMD -0.51, 95% CI -0.98 to -0.03), whereas other interventions had an effect on pain intensity but not on pain-related disability. Conclusion: Rehabilitation interventions, and psychological interventions in particular, seem to be of value for patients with chronic neuropathic pain.

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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.

Objectives: Opioid analgesics are essential in clinical practice, but their excessive use is associated with addiction risk. Increases in opioid prescription rates have fuelled an epidemic of opioid addiction in the USA, making statistics on medical opioid use a critical warning signal. A dramatic 150% increase in Swedish opioid access 2001-2013 was recently reported based on data from the International Narcotics Control Board (INCB; Berterame et al. 2016) in conflict with other studies of opioid use in the Nordic countries. This article aims to analyse to what degree published INCB statistics on opioids in Scandinavia (Denmark, Norway and Sweden) reflect actual medical use and study the methodological reasons for putative discrepancies. Methods: Data on aggregated total national sales of opioids for the whole population, including hospitals, were collected from the Swedish e-Health Authority. Total sales data for Denmark and drugs dispensed at pharmacies in Norway are publicly available through the relevant authorities websites. Results: INCB opioid statistics during the period 2001-2013 were markedly inconsistent with sales data from Scandinavia, calling the reliability of INCB data into question. INCB-data were flawed by (a) over-representing the volume of fentanyl, (b) under-reporting of codeine, and (c) by not including tramadol. Conclusions: Opioid availability, as expressed by INCB statistics, does not reflect medical opioid use. It is crucial to underline that INCB statistics are based on the manual compilation of national production, import and export data from manufacturers and drug companies. This is not the same amount that is prescribed and consumed within the health care system. Moreover, there are methodological problems in the INCB reports, in particular concerning fentanyl, codeine and tramadol. We suggest that INCB should carefully review the quality of their data on medical opioids.

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.

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.

The Swedish Quality Registry for Pain rehabilitation (SQRP) is a well-established clinical registry for adult patients with complex chronic pain conditions. SQRP registers patient-reported outcome measures from a majority of specialist chronic pain units/departments in Sweden. Up to four International Classification of Diseases version 10 (ICD-10) diagnoses can be registered in SQRP. The aim of the paper is to describe how we envision the new chronic pain category MG30 in ICD-11 can be used in SQRP. We envision that the first diagnosis in SQRP shall always be a MG30 diagnosis, which will ensure broad implementation of ICD-11 in Swedish pain care. However, at first glance, there seems to be specificity problems with ICD-11 codes that might impair their useability in SQRP or other registries. But ICD-11 offers more than meets the eye. First, the entries at the level of the so-called foundational layer have unique resource identifiers (URI) that can be used to enhance specificity. Second, ICD-11 contains numerous extension codes that can be combined with the MG30 codes - for instance, concerning the anatomical location of pain. Third, to enrich the description of the clinical concept at hand, it is possible to create clusters of stem codes. These three options are briefly discussed. We conclude that the full potential of the MG30 category can be better exploited in registries such as SQRP if foundational codes, extension codes, and/or clustering of stem codes are used to enhance diagnostic specificity.

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.

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.