Antibody-mediated autoimmunity in symptom-based disorders: position statement and proceedings from an international workshop.

A 2-day closed workshop was held in Liverpool, United Kingdom, to discuss the results of research concerning symptom-based disorders (SBDs) caused by autoantibodies, share technical knowledge, and consider future plans. Twenty-two speakers and 14 additional participants attended. This workshop set out to consolidate knowledge about the contribution of autoantibodies to SBDs. Persuasive evidence for a causative role of autoantibodies in disease often derives from experimental "passive transfer" approaches, as first established in neurological research. Here, serum immunoglobulin (IgM or IgG) is purified from donated blood and transferred to rodents, either systemically or intrathecally. Rodents are then assessed for the expression of phenotypes resembling the human condition; successful phenotype transfer is considered supportive of or proof for autoimmune pathology. Workshop participants discussed passive transfer models and wider evidence for autoantibody contribution to a range of SBDs. Clinical trials testing autoantibody reduction were presented. Cornerstones of both experimental approaches and clinical trial parameters in this field were distilled and presented in this article. Mounting evidence suggests that immunoglobulin transfer from patient donors often induces the respective SBD phenotype in rodents. Understanding antibody binding epitopes and downstream mechanisms will require substantial research efforts, but treatments to reduce antibody titres can already now be evaluated.

Complex regional pain syndrome: advances in epidemiology, pathophysiology, diagnosis, and treatment.

Complex regional pain syndrome (CRPS) is a rare pain disorder that usually occurs in a limb after trauma. The features of this disorder include severe pain and sensory, autonomic, motor, and trophic abnormalities. Research from the past decade has offered new insights into CRPS epidemiology, pathophysiology, diagnosis, and treatment. Early identification of individuals at high risk of CRPS is improving, with several risk factors established and some others identified in prospective studies during the past 5 years. Better understanding of the pathophysiological mechanisms of CRPS has led to its classification as a chronic primary pain disorder, and subtypes of CRPS have been updated. Procedures for diagnosis have also been clarified. Although effective treatment of CRPS remains a challenge, evidence-based integrated management approaches provide new opportunities to improve patient care. Further advances in diagnosis and treatment of CRPS will require coordinated, international multicentre initiatives.

Small fibre pathology, small fibre symptoms and pain in fibromyalgia syndrome.

A proportion of people with fibromyalgia demonstrate small fibre pathology (SFP). However, it is unclear how SFP directly relates to pain phenomenology. Thirty-three individuals with FMS and ten healthy volunteers underwent assessment of SFP and sensory phenotyping using corneal confocal microscopy, validated questionnaires and quantitative sensory testing (QST). Corneal nerve fibre length was used to stratify participants with fibromyalgia into with SFP [SFP+] and without SFP [SFP-]. SFP was detected in 50% of the fibromyalgia cohort. Current pain score and QST parameters did not differ between SFP+ and SFP-. Mechanical pain sensitivity (MPS) demonstrated a significant gain-of-function in the SFP- cohort compared to healthy-volunteers (p = 0.014, F = 4.806, η2 = 0.22). Further stratification revealed a cohort without structural SFP but with symptoms compatible with small fibre neuropathy symptoms and a significant gain in function in MPS (p = 0.020 Chi-square). Additionally, this cohort reported higher scores for both depression (p = 0.039, H = 8.483, η2 = 0.312) and anxiety (p = 0.022, F = 3.587, η2 = 0.293). This study confirms that SFP is present in a proportion of people with fibromyalgia. We also show that in a proportion of people with fibromyalgia, small fibre neuropathy symptoms are present in the absence of structural SFP. Greater mechanical pain sensitivity, depression and anxiety are seen in these individuals.

Results from an expedited spinal nerve root block clinic at a UK tertiary neurosurgical centre.

STUDY DESIGN: Retrospective Observational Study. INTRODUCTION: Lumbar radicular pain has a prevalence of 3-5%. Level 1 evidence has demonstrated equivalence between surgical and injection treatment. We assess the outcomes from a transforaminal epidural steroid injection clinic in a tertiary neuroscience referral centre. METHODS: We performed an analysis of data from consecutive patients entered into a new internal referral database between August 2018 to May 2021. Radicular pain was classified as one of "first presentation" or "recurrence". Outcomes were obtained from follow up clinic letters and recorded in a binary manner of "positive result" or "negative result". Spinal pathology was documented from radiology reports and MRI images. RESULTS: We analysed 208 patients referred to the clinic. Excluding those who improved to a point of not requiring treatment, and those who underwent surgical intervention, 119 patients undergoing injection were included, of which 14 were lost to follow-up. 68 % of patients had a positive result from injection. Subgroup analysis demonstrated good outcomes for both hyperacute (<6 weeks) and chronic (>12 months). Contained disk pathologies had better outcomes than uncontained. There was no difference in outcomes across grades of compression, but previous same level surgery was associated with poorer response rates. CONCLUSIONS: There is a high rate of natural resolution of symptoms in patients with LSRP. In those where pain persists, TFESI is a valuable first line treatment modality. This study suggests the efficacy of TFESI is potentially independent of grade of stenosis and chronicity of symptoms. Contained disc pathologies respond better than uncontained.

Evidence of a genetic background predisposing to complex regional pain syndrome type 1.

BACKGROUND: Complex regional pain syndrome type 1 (CRPS-1) is a rare, disabling and sometimes chronic disorder usually arising after a trauma. This exploratory study examined whether patients with chronic CRPS-1 have a different genetic profile compared with those who do not have the condition. METHODS: Exome sequencing was performed to seek altered non-synonymous SNP allele frequencies in a discovery cohort of well-characterised patients with chronic CRPS-1 (n=34) compared with population databases. Identified SNP alleles were confirmed by Sanger sequencing and sought in a replication cohort (n=50). Gene expression of peripheral blood macrophages was assessed. RESULTS: In the discovery cohort, the rare allele frequencies of four non-synonymous SNPs were statistically increased. The replication cohort confirmed this finding. In a chronic pain cohort, these alleles were not overexpressed. In total, 25 out of 84 (29.8%) patients with CRPS-1 expressed a rare allele. The SNPs were rs41289586 in ANO10, rs28360457 in P2RX7, rs1126930 in PRKAG1 and rs80308281 in SLC12A9. Males were more likely than females to have a rare SNP allele, 8 out of 14 (57.1%) vs 17 out of 70 (24.3%) (Fisher's p=0.023). ANO10, P2RX7, PRKAG1 and SLC12A9 were all expressed in macrophages from healthy human controls. CONCLUSION: A single SNP in each of the genes ANO10, P2RX7, PRKAG1 and SLC12A9 was associated with developing chronic CRPS-1, with more males than females expressing these rare alleles. Our work suggests the possibility that a permissive genetic background is an important factor in the development of CRPS-1.

Study protocol for a randomised controlled trial to investigate the effectiveness of thoracic epidural and paravertebral blockade in reducing chronic post-thoracotomy pain: 2 (TOPIC 2).

BACKGROUND: Thoracotomy is considered one of the most painful surgical procedures and can cause debilitating chronic post-surgical pain lasting months or years postoperatively. Aggressive management of acute pain resulting from thoracotomy may reduce the likelihood of developing chronic pain. This trial compares the two most commonly used modes of acute analgesia provision at the time of thoracotomy (thoracic epidural blockade (TEB) and paravertebral blockade (PVB)) in terms of their clinical and cost-effectiveness in preventing chronic post-thoracotomy pain. METHODS: TOPIC 2 is a multi-centre, open-label, parallel group, superiority, randomised controlled trial, with an internal pilot investigating the use of TEB and PVB in 1026 adult (≥ 18 years old) patients undergoing thoracotomy in up to 20 thoracic centres throughout the UK. Patients (N = 1026) will be randomised in a 1:1 ratio to receive either TEB or PVB. During the first year, the trial will include an integrated QuinteT (Qualitative Research Integrated into Trials) Recruitment Intervention (QRI) with the aim of optimising recruitment and informed consent. The primary outcome is the incidence of chronic post-surgical pain at 6 months post-randomisation defined as 'worst chest pain over the last week' equating to a visual analogue score greater than or equal to 40 mm indicating at least a moderate level of pain. Secondary outcomes include acute pain, complications of regional analgesia and surgery, health-related quality of life, mortality and a health economic analysis. DISCUSSION: Both TEB and PVB have been demonstrated to be effective in the prevention of acute pain following thoracotomy and nationally practice is divided. Identification of which mode of analgesia is both clinically and cost-effective in preventing chronic post-thoracotomy pain could ameliorate the debilitating effects of chronic pain, improving health-related quality of life, facilitating return to work and caring responsibilities and resulting in a cost saving to the NHS. TRIAL REGISTRATION: NCT03677856 [ClinicalTrials.gov] registered September 19, 2018. https://clinicaltrials.gov/ct2/show/NCT03677856 . First patient recruited 8 January 2019.

Understanding, diagnosing, and treating Myalgic encephalomyelitis/chronic fatigue syndrome - State of the art: Report of the 2nd international meeting at the Charité Fatigue Center.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating disease affecting millions of people worldwide. Due to the 2019 pandemic of coronavirus disease (COVID-19), we are facing a significant increase of ME/CFS prevalence. On May 11th to 12th, 2023, the second international ME/CFS conference of the Charité Fatigue Center was held in Berlin, Germany, focusing on pathomechanisms, diagnosis, and treatment. During the two-day conference, more than 100 researchers from various research fields met on-site and over 700 attendees participated online to discuss the state of the art and novel findings in this field. Key topics from the conference included: the role of the immune system, dysfunction of endothelial and autonomic nervous system, and viral reactivation. Furthermore, there were presentations on innovative diagnostic measures and assessments for this complex disease, cutting-edge treatment approaches, and clinical studies. Despite the increased public attention due to the COVID-19 pandemic, the subsequent rise of Long COVID-19 cases, and the rise of funding opportunities to unravel the pathomechanisms underlying ME/CFS, this severe disease remains highly underresearched. Future adequately funded research efforts are needed to further explore the disease etiology and to identify diagnostic markers and targeted therapies.

Sham controls in device trials for chronic pain - tricky in practice-a review article.

Background: Chronic pain affects one in four people and this figure is likely to increase further in line with an ageing population. Efforts to evaluate nonpharmacological interventions to support this patient population have become a priority for pain research. For device trials, the use of a sham control can add to the scientific validity and quality of a study. However, only a small proportion of pain trials include a sham control, and many are of poor quality. To facilitate the conduct of high-quality trials there is a need for a comprehensive overview to guide researchers within this area. The objective of this review was to synthesise the published data to address this need. Methods: We identified studies that considered the evaluation, design, and conduct of sham-controlled trials in chronic pain by searching MEDLINE, CINAHL and Science Direct to November 2022. Studies that included sufficient content to inform the conduct/design of future research were included. An inductive thematic analysis approach was used to identify themes that require consideration when conducting sham-controlled trials. These are presented as a narrative review. Results: 37 articles were included. Identified themes related to the type of sham device, sham design, bias, study population and ethics. Conclusions: To conduct good quality research the challenges surrounding the use of sham interventions need to be better considered. We highlight salient issues and provide recommendations for the conduct and reporting of sham-controlled device trials in chronic pain.

Global series: Complex regional pain syndrome: abstracts from the International Association for the Study of Pain complex regional pain syndrome SIG virtual symposia 2021.

The aim of this IASP complex regional pain syndrome (CRPS) SIG Global Series 2021 was to bring together clinicians including those from developing countries to better understand the clinical presentation of complex regional pain syndrome in countries with less well-published patient populations. The purpose was to learn from each other about the range of treatments, successful outcomes, and challenges experienced. These meeting proceedings comprise abstracts from nine countries that span 4 continents and are summaries of online presentations delivered by speakers representing these countries over the course of 2 symposia. The symposia were attended by a global audience of approximately 360 people. Patients with CRPS were described and treated by clinicians from countries across Asia (Pakistan, Jordan, South Korea, Taiwan, and Singapore), South America (Brazil and Peru), Africa (South Africa), and Europe (Norway). This reflects that CRPS exists across borders, ethnicities, and cultures. These proceedings provide a broader perspective within the international pain community about how we can better understand and treat CRPS across the globe.

The biology of symptom-based disorders - time to act.

Symptom-based disorders are conditions that are characterised mostly by somatic symptoms rather than objectively identifiable signs. They are very common, including pain and fatigue disorders, functional gastrointestinal and respiratory disorders, and others, and they cause far greater disability than diseases where signs are prominent. Such conditions may sometimes be triggered by infection, as in Post Covid Syndrome (Cabral-Marques et al., 2022; Baiocchi et al., 2022) or physical or psychological trauma. By employing passive immunoglobulin transfer experimental approaches, recent research in several 'unexplained' chronic pain conditions has demonstrated that pathogenic IgG autoantibodies can explain several of these conditions' core symptoms and are ubiquitous in patients with severe phenotypes. The promise from placing positive resources into exploring the role of 'invisible', functional, non-inflammatory autoantibodies in symptom-based disorders across additional areas of Medicine includes patient empowerment and the development of new diagnostic tests and therapies.

Delphi study to define core clinical outcomes for inclusion in a complex regional pain syndrome international research registry and data bank.

ABSTRACT: Complex regional pain syndrome (CRPS) clinical trials have historically captured a diverse range of outcomes. A minimum set of CRPS patient-reported outcomes has been agreed for inclusion in a future CRPS international clinical research registry and data bank. This study aimed to identify a complementary set of core clinical outcomes. Clinicians and researchers from the international CRPS community informed the content of a 2-round electronic Delphi study. Participation was invited from members of the International Association for the Study of Pain CRPS Special Interest Group and the International Research Consortium for CRPS. In round 1, participants rated the relevance of 59 clinical outcomes in relation to the question "What is the clinical presentation and course of CRPS, and what factors influence it?" (1 = not relevant and 9 = highly relevant). In round 2, participants rerated each outcome in the light of the round 1 median scores. The criterion for consensus was median score ≥7, agreed by 75% of respondents. The core study team considered the feasibility of data collection of each identified outcome in agreeing final selections. Sixty respondents completed both survey rounds, with responses broadly consistent across professions. Nine outcomes met the consensus criterion. Final outcomes recommended for inclusion in the core clinical set were record of medications, presence of posttraumatic stress disorder, extent of allodynia, and skin temperature difference between limbs. Study findings provide robust recommendations for core clinical outcome data fields in the future CPRS international clinical research registry. Alongside patient-reported outcomes, these data will enable a better understanding of CRPS.

Human Auto-IgG Purification from High Volume Serum Sample by Protein G Affinity Purification.

Immunoglobulins are proteins produced by the immune system, which bind specifically to the antigen that induced their formation and target it for destruction. Highly purified human immunoglobulins are commonly used in research laboratories for several applications, such as in vitro to obtain hybridomas and in vivo animal immunisation. Several affinity purification methods are used to purify immunoglobulins from human serum, such as protein A/G Sepharose beads, polyethylene glycol, and caprylic acid ammonium sulphate precipitation. Here, we provide a detailed protocol for purification of high-quality IgG from human serum, using affinity chromatography with protein G. The protocol is divided into four main steps (column preparation, serum running, wash, and elution) for IgG purification, and two extra steps (protein dialysis and sucrose concentration) that should be performed when buffer exchange and protein concentration are required. Several IgG affinity purification methods using protein A or G are available in the literature, but protein A has a higher affinity for rabbit, pig, dog, and cat IgG, while protein G has a higher affinity for mouse and human IgG. This affinity-based purification protocol uses protein G for a highly specific purification of human IgG for animal immunization, and it is particularly useful to purify large amounts of human IgG. This protocol was validated in: Pain (2019), DOI: 10.1097/j.pain.0000000000001662 Graphical abstract IgG purification protocol. The IgG purification protocol consists of four main steps (column preparation, serum running, wash, and elution) and two extra steps (protein dialysis and concentration). a. Diluted serum is added to the protein G beads and IgG binds to the Fc receptors on protein G beads. b. Beads are washed in Hartman's solution to fully remove the complex protein mixture (multicolour shapes, as depicted in the graphical abstract). c. IgG (orange triangles, as depicted in the graphical abstract) are removed from protein G with glycine and collected in Tris buffer. d. The IgG is transferred into a semi-permeable membrane ('snake skin') and allowed to dialyse overnight for buffer exchange with a physiological solution (Hartmann's).

The diagnosis of fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is a common widespread primary pain condition, with a worldwide prevalence of 2%-4%. Recent research has revealed important evidence for changes in central and peripheral nervous system functions and immunological activity. The diagnosis of FMS can be challenging with no known clinical laboratory investigations to confirm or refute its presence. Symptoms are commonly multiple, fluctuant and may not easily align with established medical diagnostic categories. It can be difficult for patients to articulate their array of symptoms, and for both patients and healthcare professionals to fully make sense of the complexities of the condition. As such, patients may be diagnosed inaccurately with alternative conditions, delaying diagnosis by years. The recent publication of the Royal College of Physicians' guidance aims to support clinicians in the diagnosis of FMS. Its purpose is to provide succinct, relevant information for patients and clinicians about FMS and its diagnosis.

Discovery of novel targets in a complex regional pain syndrome mouse model by transcriptomics: TNF and JAK-STAT pathways.

Complex Regional Pain Syndrome (CRPS) represents severe chronic pain, hypersensitivity, and inflammation induced by sensory-immune-vascular interactions after a small injury. Since the therapy is unsatisfactory, there is a great need to identify novel drug targets. Unbiased transcriptomic analysis of the dorsal root ganglia (DRG) was performed in a passive transfer-trauma mouse model, and the predicted pathways were confirmed by pharmacological interventions. In the unilateral L3-5 DRGs 125 genes were differentially expressed in response to plantar incision and injecting IgG of CRPS patients. These are related to inflammatory and immune responses, cytokines, chemokines and neuropeptides. Pathway analysis revealed the involvement of Tumor Necrosis Factor (TNF) and Janus kinase (JAK-STAT) signaling. The relevance of these pathways was proven by abolished CRPS IgG-induced hyperalgesia and reduced microglia and astrocyte markers in pain-associated central nervous system regions after treatment with the soluble TNF alpha receptor etanercept or JAK inhibitor tofacitinib. These results provide the first evidence for CRPS-related neuroinflammation and abnormal cytokine signaling at the level of the primary sensory neurons in a translational mouse model and suggest that etanercept and tofacitinib might have drug repositioning potentials for CRPS-related pain.

Complex Regional Pain Syndrome: Practical Diagnostic and Treatment Guidelines, 5th Edition.

There have been some modest recent advancements in the research of Complex Regional Pain Syndrome, yet the amount and quality of the work in this complicated multifactorial disease remains low (with some notable exceptions; e.g., the recent work on the dorsal root ganglion stimulation). The semi-systematic (though in some cases narrative) approach to review is necessary so that we might treat our patients while waiting for "better research." This semi-systematic review was conducted by experts in the field, (deliberately) some of whom are promising young researchers supplemented by the experience of "elder statesman" researchers, who all mention the system they have used to examine the literature. What we found is generally low- to medium-quality research with small numbers of subjects; however, there are some recent exceptions to this. The primary reason for this paucity of research is the fact that this is a rare disease, and it is very difficult to acquire a sufficient sample size for statistical significance using traditional statistical approaches. Several larger trials have failed, probably due to using the broad general diagnostic criteria (the "Budapest" criteria) in a multifactorial/multi-mechanism disease. Responsive subsets can often be identified in these larger trials, but not sufficient to achieve statistically significant results in the general diagnostic grouping. This being the case the authors have necessarily included data from less compelling protocols, including trials such as case series and even in some instances case reports/empirical information. In the humanitarian spirit of treating our often desperate patients with this rare syndrome, without great evidence, we must take what data we can find (as in this work) and tailor a treatment regime for each patient.

Aftersensations and Lingering Pain After Examination in Patients with Fibromyalgia Syndrome.

BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic widespread pain condition with mixed peripheral and central contributions. Patients display hypersensitivities to a spectrum of stimuli. Patients' blunt pressure pain thresholds are typically reduced, and sometimes (∼15%) gentle brushstroke induces allodynia. However, aftersensations after these stimuli have not, to our knowledge, been reported. METHODS: We examined the perception of blunt pressure and "pleasant touch" in FMS. Patients were first interviewed and completed standard psychometric questionnaires. We then measured their sensitivity to blunt pressure and perception of pleasant touch, including aftersensations; patients were followed up for 5 days to evaluate lingering pain from blunt pressure. RESULTS: We recruited 51 patients with FMS and 16 pain-free healthy controls (HCs) at a UK Pain Management Centre. Forty-four patients completed the aftersensation protocol. Most patients reported pain after the application of less mechanical pressure than the level of pressure at which HCs reported pain; median arm and leg thresholds for the patients with FMS were 167 kPa and 233 kPa, respectively. Eighty-four percent (31/37) of patients reported ongoing pain at the site of pressure application 1 day after testing, and 49% (18/37) still perceived pain at 5 days. Aftersensations after brushstroke were common in the FMS group, reported by 77% (34/44) of patients with FMS vs 25% (4/16) of HCs; 34% (15/44) of patients, but no HCs, perceived these aftersensations as uncomfortable. For patients with FMS who experienced aftersensations, brushstroke pleasantness ratings were reduced, and the skin was often an important site of pain. CONCLUSION: Pain after blunt pressure assessment typically lingers for several days. Aftersensations after brushstroke stimulation are a previously unreported FMS phenomenon. They are associated with tactile anhedonia and might identify a clinically distinct subgroup.

Complex regional pain syndrome what is the outcome? - a systematic review of the course and impact of CRPS at 12 months from symptom onset and beyond.

BACKGROUND AND OBJECTIVE: To improve CRPS treatment, it is imperative to understand the nature, degree and relative importance of ongoing problems associated with CRPS. The objective of this systematic review was to summarize the published data concerning measures of function and impact including occupational parameters, of CRPS at 12 months from symptom onset and beyond. DATABASES AND DATA TREATMENT: MEDLINE, EmBase and PsychINFO were searched (inception to May 2021). Study cohorts were eligible if they included; adult patients with the primary complaint of CRPS ≥12 months duration, outcomes that reported change in CRPS signs and symptoms, and physical and social function. Prospero registration: CRD42021241785. RESULTS: Twenty-two included studies suggest that pain and motor dysfunction are the most dominant long-term features of CRPS, persisting for 51%-89% of patients at ≥12 months. On average for all patients who had CRPS at baseline, grip strength was found to be reduced by 25%-66%, and range of motion reduced by 20%-25% at ≥12 months. Such losses were associated with physical and social disability. Thirty to forty percent of all patients did not return to work and a further 27%-35% of persons returned to work but required some form of workplace adaptation, although the quality of this data was poor. Quality assessment highlighted limitations in the literature, such as high attrition bias and variations in diagnostic criteria. CONCLUSIONS: Results provide first-time quantitative data including specific evidence about losses to motor function and long-term compromises to work status. Results demonstrate that the ongoing impact of one episode of CRPS on limb function and work status is relatively high. SIGNIFICANCE: This review provides first-time clarity in relation to outcomes of limb function and work status associated with an episode of CRPS, beyond 12 months from onset. Results demonstrate that the long-term impact of an episode of CRPS on these outcomes is much larger than previously described, and thus also illustrates how the wider health economic impact of CRPS is not yet fully understood. We additionally highlight the need for future research that identifies long-term predictors, and treatments that can foster good functional and occupational recovery.

Percutaneous cervical cordotomy for cancer-related pain: prospective multimodal outcomes evaluation.

BACKGROUND: Percutaneous cervical cordotomy (PCC) offers pain relief to patients with unilateral treatment-refractory cancer-related pain. There is insufficient evidence about any effects of this intervention on patients' quality of life. METHOD: Comprehensive multimodal assessment to determine how PCC affects pain, analgesic intake and quality of life of patients with medically refractory, unilateral cancer-related pain.This study was set in a multidisciplinary, tertiary cancer pain service. Patient outcomes immediately following PCC were prospectively recorded. Patients were also followed up at 4 weeks. RESULTS: Outcome variables collected included: background and breakthrough pain numerical rating scores before PCC, at discharge and 4 weeks postprocedure; oral morphine equivalent opioid dose changes, Patient's Global Impression of Change, Eastern Cooperative oncology group performance status and health related quality of life score, that is, EuroQol-5 dimension-5 level (EQ-5D). CONCLUSIONS: Despite significant improvement in pain and other standard outcomes sustained at 4 weeks, there was little evidence of improvement in EQ-5D scores. In patients with terminal cancer, improved pain levels following cordotomy for cancer-related pain does not appear to translate into improvements in overall quality of life as assessed with the generic EQ-5D measure.

Research Recommendations Following the Discovery of Pain Sensitizing IgG Autoantibodies in Fibromyalgia Syndrome.

BACKGROUND: Fibromyalgia syndrome (FMS) is the most common chronic widespread pain condition in rheumatology. Until recently, no clear pathophysiological mechanism for fibromyalgia had been established, resulting in management challenges. Recent research has indicated that serum immunoglobulin Gs (IgGs) may play a role in FMS. We undertook a research prioritisation exercise to identify the most pertinent research approaches that may lead to clinically implementable outputs. METHODS: Research priority setting was conducted in five phases: situation analysis; design; expert group consultation; interim recommendations; consultation and revision. A dialogue model was used, and an international multi-stakeholder expert group was invited. Clinical, patient, industry, funder, and scientific expertise was represented throughout. Recommendation-consensus was determined via a voluntary closed eSurvey. Reporting guideline for priority setting of health research were employed to support implementation and maximise impact. RESULTS: Arising from the expert group consultation (n = 29 participants), 39 interim recommendations were defined. A response rate of 81.5% was achieved in the consensus survey. Six recommendations were identified as high priority- and 15 as medium level priority. The recommendations range from aspects of fibromyalgia features that should be considered in future autoantibody research, to specific immunological investigations, suggestions for trial design in FMS, and therapeutic interventions that should be assessed in trials. CONCLUSIONS: By applying the principles of strategic priority setting we directed research towards that which is implementable, thereby expediating the benefit to the FMS patient population. These recommendations are intended for patients, international professionals and grant-giving bodies concerned with research into causes and management of patients with fibromyalgia syndrome.