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Boundary effects of expectation in human pain perception.

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Associated Factors and Clinical Implication of Cutaneous Allodynia in Patients with Cluster Headache: A Prospective Multicentre Study.

Cutaneous allodynia (CA) is an abnormal pain in response to non-painful stimuli. In the present study, we sought to investigate the presence of CA, its associated factors, and its clinical implications in patients with cluster headache (CH). In this cross-sectional study, we analysed data from a prospective multicentre registry enrolling consecutive patients with CH. We identified CA during and between headache attacks using the 12-item Allodynia Symptom Checklist (ASC) administered during the CH bout period. Comorbid depression and anxiety were ascertained using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) scales. Headache impact was evaluated using the Headache Impact Test-6 (HIT-6). Of 119 eligible patients, 48 and two (40.3% and 1.7%) had CA during and between headache attacks, respectively. In univariable analyses, total CH duration, major depressive disorder (MDD), and generalized anxiety disorder (GAD) were associated with CA during headache attack. They remained significantly associated with CA during headache attack in multivariable analyses. Patients with CA during headache attack had higher headache impact (P = 0.002). A "50% responder" analysis showed no difference in outcome of acute and preventive treatment between patients with and without CA during headache attack. Patients with CH commonly experienced CA during headache attack, but not between headache attacks. CA during headache attack was associated with disease duration, depression, and anxiety.

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Characteristics of women with chronic pelvic pain referred to physiotherapy treatment after multidisciplinary assessment: a cross-sectional study.

Background and aims Chronic pelvic pain (CPP) in women is a complex condition that can seriously impact health and quality of life. Clinical guidelines for CPP place great demands on healthcare professionals, as they require both specialized knowledge about the pelvic area and knowledge of the mechanisms of chronic pain. To ensure best possible assessment and treatment of these women it is important to bring about more knowledge of the special CPP features. The purpose of this paper is to describe the characteristics of women with CPP evaluated at the University Hospital of North Norway, and further referred to physiotherapy. The frequency of having a history of abuse or previous pelvic surgery will also be reported, and analyses performed to investigate if subjective health status differs between women with and without these experiences. Methods We collected cross-sectional data from 62 women with CPP aged 20-65 (mean age 38.0), referred to physiotherapy after assessment by medical specialists. Data were collected by semi-structured interviews for demographic variables and medical history, and self-administered questionnaires on pain intensity, sexual function, urinary incontinence (UI), anal incontinence (AI), obstructed defecation syndrome (ODS), subjective health complaints (SHC) and symptoms of anxiety and depression. Results Pain duration of more than 10 years was reported by 42%, mean pain score was 4.7/10, and analgesics were used weekly by 48%. Previous pelvic or abdominal surgery was reported by 71%, and sick leave >12 weeks the last year by 34%. Reduced sexual desire was reported by 78%, dyspareunia by 73%, UI by 54%, AI by 23%, and obstructed defecation syndrome (ODS) by 34%. More than 90% reported musculoskeletal or pseudoneurologic complaints. Anxiety and depression scores defined as requiring treatment were reported by 40%. Abuse was reported by 50%, and associated with significantly more reports of ODS (p=0.02), more SHC (p=0.02) and higher anxiety scores (p=0.009). Analgesic use and sick leave were significantly higher both among women with a history of abuse (p=0.04 and p=0.005) and among those with previous surgery (p=0.04 and p=0.02). Women with previous surgery reported significantly lower pain intensity during intercourse than those without previous surgery (p=0.008). Conclusions Women with CPP have complex symptoms and high scores for both physical and psychological complaints. Women exposed to abuse have especially high scores related to analgesic use, sick leave, ODS, anxiety and SHC. Women with previous surgery report more analgesic use and sick leave, and lower pain intensity during intercourse, than those without previous surgery. Implications This study illustrates the complexity of CPP and highlights the need for health professionals to have specialized knowledge of the possible features of the condition. Previous abuse seems to be more associated with poor scores on several health outcomes than surgery, but this needs to be investigated further.

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The impact of comorbid pain and depression in the United States: results from a nationally representative survey.

Background and aims The co-morbidity between pain and depression is a target of interest for treatment. However most of the published literature on the topic has used clinical cohorts as the population of interest. The goal of this study was to use a nationally representative sample to explore how health outcomes varied across pain and depression status in a cohort sampled from the general US population. Methods This was a cross-sectional analysis of adults ≥18 years in the 2009-2010 National Health and Nutrition Examination Survey. The cohort was stratified into: no pain/depression, pain alone, depression alone, and pain with depression. The primary outcome was self-reported general health status, and secondary outcomes were healthcare visits, overnight hospital stays and functional limitation. Survey weighted logistic regression was used to adjust for potential confounders. Results The cohort consisted of 4,213 individuals, of which 186 (4.4%) reported concurrent pain and depression. 597 (14.2%) and 253 (6.0%) were classified with either pain or depression alone, respectively. The majority of individuals with co-morbid pain and depression reported poor health (65.1%, p<0.001) and were significantly more likely than those with neither condition to rate their health as poor after adjustment (OR: 7.77, 95% CI: 4.24-14.26, p<0.001). Those with pain only or depression only were also more likely to rate their health as poor, albeit to a lesser extent (OR: 2.21, 95% CI: 1.21-2.34, p<0.001; OR: 3.75, 95% CI: 2.54-5.54, p<0.001, respectively). A similar pattern was noted across all secondary outcomes. Most notably, those with co-morbid pain and depression were the most likely to endorse functional limitation (OR: 13.15, 95% CI: 8.00-21.61, p<0.001). Comparatively, a similar trend was noted amongst those with pain only or depression only, though with a reduced effect size (OR: 4.23, 95% CI: 3.12-4.77, p<0.001; OR: 5.13, 95% CI: 3.38-7.82, p<0.001). Conclusions Co-morbid pain and depression in the general population resulted in markedly worse outcomes versus isolated pain or depression. Further, the effect appears to be synergistic. Given the substantial burdens of pain and depression, future treatments should aim to address both conditions simultaneously. Implications As a result of the co-morbidity between pain and depression, patients presenting with either condition should increase the index of suspicion among clinicians and prompt screening for the reciprocal condition. Early intervention for co-morbid pain and depression has the potential to mitigate future incidence of chronic pain and major depression.

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Systemic inflammation firmly documented in chronic pain patients by measurement of increased levels of many of 92 inflammation-related proteins in blood – normalizing as the pain condition improves with CBT-based multimodal rehabilitation at Uppsala Pain

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Predictive models for short-term and long-term improvement in women under physiotherapy for chronic disabling neck pain: a longitudinal cohort study.

To develop predictive models for short-term and long-term clinically important improvement in women with non-specific chronic disabling neck pain during the clinical course of physiotherapy.

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Symptom reduction and improved function in chronic CRPS type 1 after 12-week integrated, interdisciplinary therapy.

Background and aims Complex Regional Pain Syndrome (CRPS) often recovers spontaneously within the first year, but when it becomes chronic, available rehabilitative therapies (pharmacological management, physiotherapy, and psychological intervention) have limited effectiveness. This study examined the effect of a 12-week intensive outpatient rehabilitation on pain relief and function in chronic CRPS patients. Rehabilitation program included memantine and morphine treatment (added to patient's prior pain medication) and concurrent psychological and physiotherapeutic intervention. Primary outcome measure was a change in CRPS symptom count and secondary outcomes were motor performance, psychological factors, pain intensity, and quality of life. Methods Ten patients with chronic upper limb CRPS I (median 2.9 years, range 8 months to 12 years) were recruited to the study and were assessed before and after the intervention. Hand motor function of the patients was evaluated by an independent physiotherapist. There were standardized questionnaires for depression, pain anxiety, pain acceptance, quality of life, and CRPS symptom count. In addition, psychological factors were evaluated by a semi-structured interview. Severity of experienced pain was rated at movement and at rest. In addition, a video experiment of a hand action observation was conducted pre- and post-intervention to study possible change in neuronal maladaptation. Intervention consisted of pharmacological, psychological and physiotherapeutic treatment. First, 10 mg daily morphine was started and increased gradually to 30 mg daily, if tolerated. After 30 mg/day or tolerated dose of morphine was achieved, 5 mg daily memantine was started and increased gradually to 40 mg, if tolerated. Psychological intervention consisted of weekly group sessions, using cognitive and behavioral methods (relaxation, behavioral activation, and exposure) and acceptance and commitment therapy (ACT) and daily home practice. Physiotherapeutic intervention consisted of graded motor imagery and physiotherapy exercises with weekly group sessions and/or individual guidance by the physiotherapist, and individual exercise of the affected upper limb. Results Multimodal intensive intervention resulted in significant decrease in CRPS symptom count. The effect was strongest in motor and trophic symptoms (19% decrease after intervention) and in sensory symptoms (18% decrease). Additionally, improvement was seen in some, but not all, secondary outcomes (movement pain, motor symptoms, change in perceptions during video experiment of hand actions, and summary index with motor functioning, pain, and psychological factors). There were no dropouts. Conclusions Intensive 12-week multimodal intervention reduced some CRPS symptoms but was not sufficient to alter patients' rest pain, distress, or quality of life. Implications These results support the efficacy of an interdisciplinary rehabilitation program for pain and function in chronic CRPS patients. After intervention, some CRPS symptoms reduced and function improved, but distress and quality of life were unchanged. This may be due to the relatively short duration of this program; to delayed effects; to particular cognitive problems of CPRS patients; and/or to low distress levels at baseline that make statistically significant reduction less likely.

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The Oslo University Hospital Pain Registry: development of a digital chronic pain registry and baseline data from 1,712 patients.

Background and aims Chronic pain is a leading cause to years lived with disability worldwide. However, few of the interventions used in pain medicine have proven efficacy, and evidence from the existing studies may not be valid for the general pain population. Therefore, it is of utmost need that we describe chronic pain conditions in their most relevant aspects, their various guises, as well as the real world outcomes of our clinical interventions. The most obvious and crude way to make these assessments are through large registries where patient characteristics, treatment characteristics (including but not limited to what, when, how often and by whom), treatment outcomes and patient outcomes are scrutinized and recorded. Methods and results This article describes in detail the design and baseline data of the comprehensive Oslo University Hospital Pain Registry (OPR). OPR is the local registry of the largest university and interdisciplinary outpatient pain clinic in Norway. Data registration started in October 2015, and approximately 1,000 patients are assessed and treated at the clinic each year. During the first 2 years of running the OPR (through September 2017), a total of 1,712 patient baseline reports were recorded from 2,001 patients. Clinicians enter data about relevant treatments and interventions, while patients provide self-reported data on aspects related to pain and pain management. The patients complete an electronic registration immediately before their first consultation at the outpatient pain clinic. The baseline questions of the OPR cover: Basic demographics; The Modified Oswestry Disability Index to assess general function; A pain drawing to assess pain location; Questions regarding the temporal aspects of pain; Six 0-10 Numeric Rating Scales to assess pain intensity and bothersomeness; The EQ-5D-5L to measure health-related quality of life; The Hopkins Symptom Check List-25 to assess psychological distress; A single question about self-rated health; The general self-efficacy scale to assess the patient's perceived self-efficacy; The Bodily Distress Syndrome checklist to assess functional disorders; The Injustice Experience Questionnaire to assess whether the patients experience injustice; Chalder Fatigue Questionnaire to assess fatigue; The Insomnia Severity Index to assesses the levels of insomnia symptoms; The Pain Catastrophizing Scale to measure pain catastrophizing and exaggerated negative orientation toward pain stimuli and pain experience; And the SF36v2 to assess patients' self-report of generic health and wellbeing. The baseline data show that chronic pain patients have a high degree of negative impact in all aspects of their lives. Conclusions and implications The OPR is the most comprehensive pain registry for multidisciplinary and interdisciplinary outpatient pain clinics in Norway. Detailed design of the registry and key baseline data are presented. Registries are of great value in that they enable real world effectiveness outcomes for patients with chronic pain conditions. The OPR can thus serve as a model for similar initiatives elsewhere. The OPR cohort may also serve as a historical control in future studies, both with experimental and observational design.

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Prescribed opioid analgesic use developments in three Nordic countries, 2006-2017.

Background and aims While the Nordic countries have considerably stricter controls on opioid prescribing for chronic non-cancer pain than other countries, previous research has warned that prescription of strong opioids is increasing. This study examines consumption of and developments in dispensed prescribed opioids to individuals receiving ambulatory care from 2006 to 2017, using publicly available data from each of three Nordic countries' national prescription registries. Methods Repeated, cross-sectional design. One-year prevalence of all dispensed prescribed opioids in ATC N02A group were reported for Norway, Denmark, and Sweden in the period 2006-2017 by gender. One-year prevalence of the weak opioids tramadol and codeine and the strong opioid oxycodone were then reported separately over this period for each country. The mean defined daily dose (DDD) per user per year, an estimate of the amount of opioids prescribed, was reported for each of the three opioids in 2016. Results Patterns of dispensed prescribed opioids differ greatly between 2006 and 2017 and between countries, with tramadol increasing in Norway, codeine declining across the board, and oxycodone increasing in all three countries. Norway exceeded Sweden and Denmark in prevalence of all dispensed prescribed opioids, with 12.1% of the female Norwegian population and 9.2% of the male Norwegian population dispensed at least one prescribed opioid as an outpatient in 2016. Norway's high overall prevalence rates are tempered by dispensing the lowest mean doses of both weak opioids compared to Sweden. Similarly, Sweden dispenses the lowest mean doses of oxycodone but to the largest proportion of its population (3.0%). Conclusions Significant shifts have occurred in the dispensing of prescribed opioids in Norway, Sweden, and Denmark over the past 12 years. The increasing prevalence of oxycodone in all three countries should continue to be monitored. Prescription registries provide a wealth of publicly available data that can be used to monitor and to guide prescribing policies in a more knowledge-based direction.

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Detection of systemic inflammation in severely impaired chronic pain patients and effects of a multimodal pain rehabilitation program.

Background and aims Recent research indicates a previously unknown low-grade systemic or neurogenic inflammation in groups of chronic pain (CP) patients. Low-grade inflammation may have an important role in symptoms that have previously not been well depicted: widespread pain, tiredness and cognitive dysfunctions frequently seen in severely impaired CP patients. This study aimed to investigate the plasma inflammatory profile in a group of very complex CP patients at baseline and at a 1-year follow-up after participation in a cognitive behavior therapy (CBT)-based multimodal pain rehabilitation program (PRP). Methods Blood samples were collected from 52 well-characterized CP patients. Age- and sex-matched healthy blood donors served as controls. The samples were analyzed with a multiple Proximal Extension Analysis allowing a simultaneous analysis of 92 inflammation-related proteins consisting mainly of cytokines, chemokines and growth-factors. At follow-up, 1-year after participation in the RPR samples from 28 patients were analyzed. The results were confirmed by a multi-array technology that allows quantitative estimation. Results Clear signs of increased inflammatory activity were detected in the CP patients. Accepting a false discovery rate (FDR) of 5%, there were significant differences in 43/92 inflammatory biomarkers compared with the controls. In three biomarkers (CXCL5, SIRT2, AXIN1) the expression levels were elevated more than eight times. One year after the PRP, with the patients serving as their own controls, a significant decrease in overall inflammatory activity was found. Conclusions Our results indicate that the most impaired CP patients suffer from low-grade chronic systemic inflammation not described earlier with this level of detail. The results may have implications for a better understanding of the cluster of co-morbid symptoms described as the "sickness-syndrome" and the wide-spread pain seen in this group of patients. The decrease in inflammatory biomarkers noted at the follow-up after participation in the PRP may reflect the positive effects obtained on somatic and psycho-social mechanisms involved in the inflammatory process by a rehabilitation program. Besides the PRP, no major changes in medication or lifestyle factors were implemented during the same period. To our knowledge, this is the first study reporting that a PRP may induce inflammatory-reducing effects. Further studies are needed to verify the objective findings in CP patients and address the question of causality that remains to be solved. Implications The findings offer a new insight into the complicated biological processes underlying CP. It may have implications for the understanding of symptoms collectively described as the "sickness-syndrome" – frequently seen in this group of patients. The lowering of cytokines after the participation in a PRP indicate a new way to evaluate this treatment; by measuring inflammatory biomarkers.

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