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Nociplastic pain is the semantic term suggested by the international community of pain researchers to describe a third category of pain that is mechanistically distinct from nociceptive pain, which is caused by ongoing inflammation and damage of tissues, and neuropathic pain, which is caused by nerve damage. The mechanisms that underlie this type of pain are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles. The symptoms observed in nociplastic pain include multifocal pain that is more widespread or intense, or both, than would be expected given the amount of identifiable tissue or nerve damage, as well as other CNS-derived symptoms, such as fatigue, sleep, memory, and mood problems. This type of pain can occur in isolation, as often occurs in conditions such as fibromyalgia or tension-type headache, or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain, as might occur in chronic low back pain. It is important to recognise this type of pain, since it will respond to different therapies than nociceptive pain, with a decreased responsiveness to peripherally directed therapies such as anti-inflammatory drugs and opioids, surgery, or injections.

Multiple clinical and epidemiological studies have provided estimates of fibromyalgia prevalence and sex ratio, but different criteria sets and methodology, as well as bias, have led to widely varying (0.4%->11%) estimates of prevalence and female predominance (>90% to <61%). In general, studies have failed to distinguish Criteria based fibromyalgia (CritFM) from Clinical fibromyalgia (ClinFM). In the current study we compare CritFM with ClinFM to investigate gender and other biases in the diagnosis of fibromyalgia. We used a rheumatic disease databank and 2016 fibromyalgia criteria to study prevalence and sex ratios in a selection biased sample of 1761 referred and diagnosed fibromyalgia patients and in an unbiased sample of 4342 patients with no diagnosis with respect to fibromyalgia. We compared diagnostic and clinical variables according to gender, and we reanalyzed a German population study (GPS) (n = 2435) using revised 2016 criteria for fibromyalgia. In the selection-biased sample of referred patients with fibromyalgia, more than 90% were women. However, when an unselected sample of rheumatoid arthritis (RA) patients was studied for the presence of fibromyalgia, women represented 58.7% of fibromyalgia cases. Women had slightly more symptoms than men, including generalized pain (36.8% vs. 32.4%), count of 37 symptoms (4.7 vs. 3.7) and mean polysymptomatic distress scores (10.2 vs. 8.2). We also found a linear relation between the probability of being females and fibromyalgia and fibromyalgia severity. Women in the GPS represented 59.2% of cases. The perception of fibromyalgia as almost exclusively (≥90%) a women's disorder is not supported by data in unbiased studies. Using validated self-report criteria and unbiased selection, the female proportion of fibromyalgia cases was ≤60% in the unbiased studies, and the observed CritFM prevalence of fibromyalgia in the GPS was ~2%. ClinFM is the public face of fibromyalgia, but is severely affected by selection and confirmation bias in the clinic and publications, underestimating men with fibromyalgia and overestimating women. We recommend the use of 2016 fibromyalgia criteria for clinical diagnosis and epidemiology because of its updated scoring and generalized pain requirement. Fibromyalgia and generalized pain positivity, widespread pain (WPI), symptom severity scale (SSS) and polysymptomatic distress (PSD) scale should always be reported.

Background To perform a systematic review and meta-analysis on cytokine levels in patients with fibromyalgia syndrome (FMS). Methods Through December 2010 we systematically reviewed the databases PubMed, MEDLINE, and PsycINFO and screened the reference lists of 22 review articles for suitable original articles. Original articles investigating cytokines in patients with FMS were included. Data were extracted by two independent authors. Differences of the cytokine levels of FMS patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed applying methodological scores: modified Center of Evidence Based Medicine, Newcastle-Ottawa-Scale, and Würzburg Methodological Quality Score. Results Twenty-five articles were included investigating 1255 FMS patients and 800 healthy controls. Data of 13/25 studies entered meta-analysis. The overall methodological quality of studies was low. The results of the majority of studies were not comparable because methods, investigated material, and investigated target cytokines differed. Systematic review of the selected 25 articles revealed that FMS patients had higher serum levels of interleukin (IL)-1 receptor antagonist, IL-6, and IL-8, and higher plasma levels of IL-8. Meta-analysis of eligible studies showed that FMS patients had higher plasma IL-6 levels compared to controls (SMD = -0.34 [-0.64, -0.03] 95% CI; p = 0.03). The majority of investigated cytokines were not different between patients and controls. Conclusions The pathophysiological role of cytokines in FMS is still unclear. Studies of higher quality and with higher numbers of subjects are needed.

Fibromyalgia is a common illness characterized by chronic widespread pain, sleep problems (including unrefreshing sleep), physical exhaustion and cognitive difficulties. The definition, pathogenesis and treatment are controversial, and some even contest the existence of this disorder. In 1990, the American College of Rheumatology (ACR) defined classification criteria that required multiple tender points (areas of tenderness occurring in muscles and muscle–tendon junctions) and chronic widespread pain. In 2010, the ACR preliminary diagnostic criteria excluded tender points, allowed less extensive pain and placed reliance on patient-reported somatic symptoms and cognitive difficulties. Fibromyalgia occurs in all populations worldwide, and symptom prevalence ranges between 2% and 4% in the general population. The prevalence of people who are actually diagnosed with fibromyalgia (‘administrative prevalence’) is much lower. A model of fibromyalgia pathogenesis has been suggested in which biological and psychosocial variables interact to influence the predisposition, triggering and aggravation of a chronic disease, but the details are unclear. Diagnosis requires the history of a typical cluster of symptoms and the exclusion of a somatic disease that sufficiently explains the symptoms by medical examination. Current evidence-based guidelines emphasize the value of multimodal treatments, which encompass both non-pharmacological and selected pharmacological treatments tailored to individual symptoms, including pain, fatigue, sleep problems and mood problems. For an illustrated summary of this Primer, visit: http://go.nature.com/LIBdDX Fibromyalgia is characterized by chronic widespread pain, unrefreshing sleep, physical exhaustion and cognitive difficulties. The definition, pathogenesis and treatment of fibromyalgia are controversial, with some physicians contesting its existence. In this Primer, Häuser et al . explain these controversies.

Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We present here a model of fibromyalgia that integrates current psychosocial and neurophysiological observations. We propose that an imbalance in emotion regulation, reflected by an overactive ‘threat’ system and underactive ‘soothing’ system, might keep the ‘salience network’ (also known as the midcingulo-insular network) in continuous alert mode, and this hyperactivation, in conjunction with other mechanisms, contributes to fibromyalgia. This proposed integrative model, which we term the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model, should be viewed as a working hypothesis with limited supporting evidence available. We hope, however, that this model will shed new light on existing psychosocial and biological observations, and inspire future research to address the many gaps in our knowledge about fibromyalgia, ultimately stimulating the development of novel therapeutic interventions.In this Perspective, the authors propose a model in which an imbalance of threat and soothing systems leads to hyperactivation of the brain’s salience network, which, in conjunction with other mechanisms, contributes to fibromyalgia.

Background Hitherto only studies with selected populations have found an increased all-cause mortality of some selected opioids compared to selected non-opioids for chronic non-cancer pain (CNCP). We have examined the all-cause mortality for CNCP associated with all established opioids compared to non-opioid analgesic therapy (anticonvulsants, antidepressants, dipyrone, non-steroidal agents). Methods The study used the InGef (Institute for Applied Health Research Berlin) database which is an anonymized healthcare claims database including 4,711,668 insured persons who were covered by 61 German statutory health insurances between 2013 and 2017.The health insurance companies are the owners of the database. All-cause mortality was determined from death certificates. Adjusted hazard ratios (HRs) including age, gender, comorbidity index, and propensity score as covariates and risk differences (RD) in incidence of death between patients with long-term opioid therapy (LTOT) and control-drug therapy were calculated. Results The mean age of participants was 66 years; 55% were women. There were 554 deaths during 10,435 person-years for the LTOT patients, whereas there were 340 deaths during 11,342 person-years in the control group. The HR for all-cause mortality was 1.59 (95% CI, 1.38–1.82) with a risk difference of 148 excess deaths (95% CI 99–198) per 10,000 person-years. The elevated risk of death for LTOT was confined to the out-of-hospital deaths: LTOT patients had 288 out-of-hospital deaths during 10,435 person-years (276 per 10,000 person-years) whereas there were 110 deaths during 11,342 person-years (97 per 10,000 person-years) in the control group. HR was 2.29 (95% CI 1.86, 2.83). Although our propensity score matching model indicated a good classification, residual confounding cannot be fully excluded. The opioid group had a higher prevalence of heart failure and a higher use of anti-thrombotic and antiplatelet agents and of psycholeptics. Conclusions LTOT for CNCP compared to non-opioid analgesics was associated with an increased risk for all-cause mortality. When considering treatment options for patients with CNCP, the relevant risk of increased all-cause mortality with opioids should be discussed. Trial registration ClinicalTrials.gov , NCT03778450, Registered on 7 December 2018

A systematic review with meta-analysis of the efficacy and safety of meditative movement therapies (Qigong, Tai Chi and Yoga) in fibromyalgia syndrome (FMS) was carried out. We screened Clinicaltrials.Gov, Cochrane Library, PsycINFO, PubMed and Scopus (through December 2010) and the reference sections of original studies for meditative movement therapies (MMT) in FMS. Randomized controlled trials (RCT) comparing MMT to controls were analysed. Outcomes of efficacy were pain, sleep, fatigue, depression and health-related quality of life (HRQOL). Effects were summarized using standardized mean differences (SMD [95% confidence interval]). Outcomes of safety were drop out because of adverse events and serious adverse events. A total of 7 out of 117 studies with 362 subjects and a median of 12 sessions (range 8–24) were included. MMT reduced sleep disturbances (−0.61 [−0.95, −0.27]; 0.0004), fatigue (−0.66 [−0.99, −0.34]; <0.0001), depression (−0.49 [−0.76, −0.22]; 0.0004) and limitations of HRQOL (−0.59 [−0.93, −0.24]; 0.0009), but not pain (−0.35 [−0.80, 0.11]; 0.14) compared to controls at final treatment. The significant effects on sleep disturbances (−0.52 [−0.97, −0.07]; 0.02) and HRQOL (−0.66 [−1.31, −0.01]; 0.05) could be maintained after a median of 4.5 (range 3–6) months. In subgroup analyses, only Yoga yielded significant effects on pain, fatigue, depression and HRQOL at final treatment. Drop out rate because of adverse events was 3.1%. No serious adverse events were reported. MMT are safe. Yoga had short-term beneficial effects on some key domains of FMS. There is a need for high-quality studies with larger sample sizes to confirm the results.

To describe and evaluate somatic symptoms in patients with rheumatoid arthritis (RA) and fibromyalgia, determine the relation between somatization syndromes and fibromyalgia, and evaluate symptom data in light of the Diagnostic and Statistical Manual-5 (DSM-5) criteria for somatic symptom disorder. We administered the Patient Health Questionnaire-15 (PHQ-15), a measure of somatic symptom severity to 6,233 persons with fibromyalgia, RA, and osteoarthritis. PHQ-15 scores of 5, 10, and 15 represent low, medium, and high somatic symptom severity cut-points. A likely somatization syndrome was diagnosed when PHQ-15 score was ≥10. The intensity of fibromyalgia diagnostic symptoms was measured by the polysymptomatic distress (PSD) scale. 26.4% of RA patients and 88.9% with fibromyalgia had PHQ-15 scores ≥10 compared with 9.3% in the general population. With each step-wise increase in PHQ-15 category, more abnormal mental and physical health status scores were observed. RA patients satisfying fibromyalgia criteria increased from 1.2% in the PHQ-15 low category to 88.9% in the high category. The sensitivity and specificity of PHQ-15≥10 for fibromyalgia diagnosis was 80.9% and 80.0% (correctly classified = 80.3%) compared with 84.3% and 93.7% (correctly classified = 91.7%) for the PSD scale. 51.4% of fibromyalgia patients and 14.8% with RA had fatigue, sleep or cognitive problems that were severe, continuous, and life-disturbing; and almost all fibromyalgia patients had severe impairments of function and quality of life. All patients with fibromyalgia will satisfy the DSM-5 \"A\" criterion for distressing somatic symptoms, and most would seem to satisfy DSM-5 \"B\" criterion because symptom impact is life-disturbing or associated with substantial impairment of function and quality of life. But the \"B\" designation requires special knowledge that symptoms are \"disproportionate\" or \"excessive,\" something that is uncertain and controversial. The reliability and validity of DSM-5 criteria in this population is likely to be low.

Different types of childhood maltreatment, like emotional abuse, emotional neglect, physical abuse, physical neglect and sexual abuse are interrelated because of their co-occurrence. Different patterns of childhood abuse and neglect are associated with the degree of severity of mental disorders in adulthood. The purpose of this study was (a) to identify different patterns of childhood maltreatment in a representative German community sample, (b) to replicate the patterns of childhood neglect and abuse recently found in a clinical German sample, (c) to examine whether participants reporting exposure to specific patterns of child maltreatment would report different levels of psychological distress, and (d) to compare the results of the typological approach and the results of a cumulative risk model based on our data set. In a cross-sectional survey conducted in 2010, a representative random sample of 2504 German participants aged between 14 and 92 years completed the Childhood Trauma Questionnaire (CTQ). General anxiety and depression were assessed by standardized questionnaires (GAD-2, PHQ-2). Cluster analysis was conducted with the CTQ-subscales to identify different patterns of childhood maltreatment. Three different patterns of childhood abuse and neglect could be identified by cluster analysis. Cluster one showed low values on all CTQ-scales. Cluster two showed high values in emotional and physical neglect. Only cluster three showed high values in physical and sexual abuse. The three patterns of childhood maltreatment showed different degrees of depression (PHQ-2) and anxiety (GAD-2). Cluster one showed lowest levels of psychological distress, cluster three showed highest levels of mental distress. The results show that different types of childhood maltreatment are interrelated and can be grouped into specific patterns of childhood abuse and neglect, which are associated with differing severity of psychological distress in adulthood. The results correspond to those recently found in a German clinical sample and support a typological approach in the research of maltreatment. While cumulative risk models focus on the number of maltreatment types, the typological approach takes the number as well as the severity of the maltreatment types into account. Thus, specific patterns of maltreatment can be examined with regard to specific long-term psychological consequences.