Is connective tissue massage effective in individuals with fibromyalgia?

OBJECTIVES: The aim of the study was to examine the effectiveness of Clinical Pilates exercises and connective tissue massage (CTM) in individuals with Fibromyalgia (FM) on pain, disease impact, functional status, anxiety, quality of life and biopsychosocial status. METHODS: 32 women were randomly divided into two groups as intervention gorup (CTM + Clinical Pilates exercises, n = 15, mean age = 48.80 ± 7.48) and control gorup (Clinical Pilates exercises, n = 17, mean age = 55.64 ± 7.87). The number of painful regions were assessed with Pain Location Inventory (PLI), disease impact with Fibromyalgia Impact Questionnare (FIQ), functional status with Health Assessment Questionnare (HAQ), anxiety with Beck Anxiety Inventory (BAI), quality of life with Short Form-36 (SF-36) and biopsychosocial status with Biopsychosocial Questionnaire (BETY-BQ) were evaluated. All evaluations were made before and after treatment. Both treatments were applied 3 times a week for 6 weeks. RESULTS: When the pre-treatment and post-treatment results are analyzed; significant difference was observed in PLI (p = 0.007; effect size 1.273), FIQ (p = 0.004; effect size 0.987), SF-36 physical component (p = 0.025; effect size -0.496) and mental component (p = 0.017; effect size -0.761) in the intervention group while the significant difference was observed in FIQ (p = 0.001; effect size 1.096) and BAI (p = 0.043; effect size 0.392), SF-36 physical component (p = 0.008; effect size -0.507) and mental component (p = 0.024; effect size -0.507) in the control group. When the delta values of the groups are compared, the difference was determined only in the PLI (p = 0.023) in favor of the intervention group. CONCLUSIONS: CTM can be effective in reducing the number of painful areas in addition to the positive effects of clinical Pilates exercises in women with FM.

Effectiveness of manual lymphatic drainage in women with fibromyalgia: A pilot study.

BACKGROUND: Currently there is no treatment capable of significantly alleviating all the symptoms of fibromyalgia (FM), even though it is a complex syndrome with a high prevalence in the population. DESIGN: Experimental study using a single-blind, randomised, clinical trial. OBJECTIVE: To analyse the efficacy of manual lymphatic drainage (MLD) as an alternative to traditional treatment of fibromyalgia (FM) in women. METHODS: This was an experimental study using a single-blind, randomised, clinical trial of 20 women between 30 and 55 years old with FM. Patients were divided into an experimental group (n = 10) and a control group (n = 10). During the study, 3 measurements of pain (visual analogue scale and algometry), FM impact (Fibromyalgia Impact Questionnaire), sleep quality (Index Pittsburgh), anxiety and depression (Hospital Anxiety and Depression Scale) were recorded. Treatment of the experimental group consisted of 2 weekly MLD sessions for 6 weeks. RESULTS: The effect of the interaction of MLD showed statistically significant results in Right intercostal space (F2,36 = 3.54; p = 0.04; n2p = 0.16). The sleep quality was significantly better favour of the treatment (F2,36 = 4.16; p = 0.01; n2p = 0.20). CONCLUSIONS: MLD therapy demonstrated effects in the experimental group in contrast to the control group across the intervention period concerning the right intercostal space and sleep-related factors. However, MLD did not result in observable alterations in pain perception.

Increased Risk of 90-Day Complications in Patients With Fibromyalgia Undergoing Total Shoulder Arthroplasty.

INTRODUCTION: Anatomic and reverse total shoulder arthroplasties (TSAs) are effective treatment options for end-stage glenohumeral osteoarthritis. Those undergoing TSA may also have fibromyalgia, a musculoskeletal condition. However, the association of fibromyalgia with shorter and longer term outcomes after TSA has not been well characterized. METHODS: Patients undergoing TSA for osteoarthritis indications were identified in the PearlDiver M165 database from January 2016 to October 2022. Exclusion criteria included age younger than 18 years, shoulder infection, neoplasm, or trauma within 90 days before surgery, and inactivity in the database within 90 days of surgery. Patients with fibromyalgia were matched in a 1:4 ratio to patients without based on age, sex, and Elixhauser Comorbidity Index. Ninety-day adverse events were compared using univariable and multivariable analyses. Five-year revision-free survival was compared using the log-rank test. RESULTS: Of 163,565 TSA patients, fibromyalgia was identified for 9,035 (5.52%). After matching, cohorts of 30,770 non-fibromyalgia patients and 7,738 patients with fibromyalgia were identified. Multivariable analyses demonstrated patients with fibromyalgia were at independently increased odds ratios (ORs) for the following 90-day complications (decreasing OR order): urinary tract infection (OR = 4.49), wound dehiscence (OR = 3.63), pneumonia (OR = 3.46), emergency department visit (OR = 3.45), sepsis (OR = 3.15), surgical site infection (OR = 2.82), cardiac events (OR = 2.72), acute kidney injury (OR = 2.65), deep vein thrombosis (OR = 2.48), hematoma (OR = 2.03), and pulmonary embolism (OR = 2.01) (P < 0.05 for each). These individual complications contributed to the increased odds of aggregated minor adverse events (OR = 3.68), all adverse events (OR = 3.48), and severe adverse events (OR = 2.68) (P < 0.05 for each). No statistically significant difference was observed in 5-year revision-free survival between groups. DISCUSSION: This study found TSA patients with fibromyalgia to be at increased risk of adverse events within 90 days of surgery. Proper surgical planning and patient counseling are crucial to this population. Nonetheless, it was reassuring that those with fibromyalgia had similar 5-year revision-free survival compared with those without.

Hyperbaric oxygen therapy vs. pharmacological intervention in adults with fibromyalgia related to childhood sexual abuse: prospective, randomized clinical trial.

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = - 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.

Functional connectivity associated with attention networks differs among subgroups of fibromyalgia patients: an observational case-control study.

Fibromyalgia is a heterogenous chronic pain disorder diagnosed by symptom-based criteria. The aim of this study was to clarify different pathophysiological characteristics between subgroups of patients with fibromyalgia. We identified subgroups with distinct pain thresholds: those with a low pressure pain threshold (PL; 16 patients) and those with a normal pressure pain threshold (PN; 15 patients). Both groups experienced severe pain. We performed resting-state functional MRI analysis and detected 11 functional connectivity pairs among all 164 ROIs with distinct difference between the two groups (p < 0.001). The most distinctive one was that the PN group had significantly higher functional connectivity between the secondary somatosensory area and the dorsal attention network (p < 0.0001). Then, we investigated the transmission pathway of pain stimuli. Functional connectivity of the thalamus to the insular cortex was significantly higher in the PL group (p < 0.01 - 0.05). These results suggest that endogenous pain driven by top-down signals via the dorsal attention network may contribute to pain sensation in a subgroup of fibromyalgia patients with a normal pain threshold. Besides, external pain driven by bottom-up signals via the spinothalamic tract may contribute to pain sensations in another group of patients with a low pain threshold. Trial registration: UMIN000037712.

Association of OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 polymorphisms with clinical phenotype among women with fibromyalgia.

To investigate the association between three selected pain polymorphisms and clinical, functional, sensory-related, psychophysical, psychological or cognitive variables in a sample of women with fibromyalgia (FMS). One hundred twenty-three (n = 123) women with FMS completed demographic (age, height, weight), clinical (years with pain, intensity of pain at rest and during daily living activities), functional (quality of life, physical function), sensory-related (sensitization-associated and neuropathic-associated symptoms), psychophysical (pressure pain thresholds), psychological (sleep quality, depressive and anxiety level) and cognitive (pain catastrophizing, kinesiophobia) variables. Those three genotypes of the OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 single nucleotide polymorphisms were obtained by polymerase chain reactions from no-stimulated whole saliva collection. No significant differences in demographic, clinical, functional, sensory-related, psychophysical, psychological and cognitive variables according to OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680 genotype were identified in our sample of women with FMS. A multilevel analysis did not either reveal any significant gene-to-gene interaction between OPRM1 rs1799971 x HTR1B rs6296, OPRM1 rs1799971 x COMT rs4680 and HTR1B rs6296 x COMT rs4680 for any of the investigated outcomes. This study revealed that three single nucleotide polymorphisms, OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680, mostly associated with chronic pain were not involved in phenotyping features of FMS. Potential gene-to-gene interaction and their association with clinical phenotype in women with FMS should be further investigated in future studies including large sample sizes.

Machine learning identifies risk factors associated with long-term opioid use in fibromyalgia patients newly initiated on an opioid.

OBJECTIVES: Fibromyalgia is frequently treated with opioids due to limited therapeutic options. Long-term opioid use is associated with several adverse outcomes. Identifying factors associated with long-term opioid use is the first step in developing targeted interventions. The aim of this study was to evaluate risk factors in fibromyalgia patients newly initiated on opioids using machine learning. METHODS: A retrospective cohort study was conducted using a nationally representative primary care dataset from the UK, from the Clinical Research Practice Datalink. Fibromyalgia patients without prior cancer who were new opioid users were included. Logistic regression, a random forest model and Boruta feature selection were used to identify risk factors related to long-term opioid use. Adjusted ORs (aORs) and feature importance scores were calculated to gauge the strength of these associations. RESULTS: In this study, 28 552 fibromyalgia patients initiating opioids were identified of which 7369 patients (26%) had long-term opioid use. High initial opioid dose (aOR: 31.96, mean decrease accuracy (MDA) 135), history of self-harm (aOR: 2.01, MDA 44), obesity (aOR: 2.43, MDA 36), high deprivation (aOR: 2.00, MDA 31) and substance use disorder (aOR: 2.08, MDA 25) were the factors most strongly associated with long-term use. CONCLUSIONS: High dose of initial opioid prescription, a history of self-harm, obesity, high deprivation, substance use disorder and age were associated with long-term opioid use. This study underscores the importance of recognising these individual risk factors in fibromyalgia patients to better navigate the complexities of opioid use and facilitate patient-centred care.

Transcranial direct current stimulation is more effective than pregabalin in controlling nociceptive and anxiety-like behaviors in a rat fibromyalgia-like model.

OBJECTIVES: Despite the fact that fibromyalgia, a widespread disease of the musculoskeletal system, has no specific treatment, patients have shown improvement after pharmacological intervention. Pregabalin has demonstrated efficacy; however, its adverse effects may reduce treatment adherence. In this context, neuromodulatory techniques such as transcranial direct current stimulation (tDCS) may be employed as a complementary pain-relieving method. Consequently, the purpose of this study was to evaluate the effect of pregabalin and tDCS treatments on the behavioral and biomarker parameters of rats submitted to a fibromyalgia-like model. METHODS: Forty adult male Wistar rats were divided into two groups: control and reserpine. Five days after the end of the administration of reserpine (1 mg/kg/3 days) to induce a fibromyalgia-like model, rats were randomly assigned to receive either vehicle or pregabalin (30 mg/kg) along with sham or active- tDCS treatments. The evaluated behavioral parameters included mechanical allodynia by von Frey test and anxiety-like behaviors by elevated plus-maze test (time spent in opened and closed arms, number of entries in opened and closed arms, protected head-dipping, unprotected head-dipping [NPHD], grooming, rearing, fecal boluses). The biomarker analysis (brain-derived neurotrophic factor [BDNF] and tumor necrosis factor-α [TNF-α]) was performed in brainstem and cerebral cortex and in serum. RESULTS: tDCS reversed the reduction in the mechanical nociceptive threshold and the decrease in the serum BDNF levels induced by the model of fibromyalgia; however, there was no effect of pregabalin in the mechanical threshold. There were no effects of pregabalin or tDCS found in TNF-α levels. The pain model induced an increase in grooming time and a decrease in NPHD and rearing; while tDCS reversed the increase in grooming, pregabalin reversed the decrease in NPHD. CONCLUSIONS: tDCS was more effective than pregabalin in controlling nociception and anxiety-like behavior in a rat model-like fibromyalgia. Considering the translational aspect, our findings suggest that tDCS could be a potential non-pharmacological treatment for fibromyalgia.

Treatment of fibromyalgia among patients with mastalgia and fibromyalgia improved mastalgia.

OBJECTIVES: The aim of this study is to examine the effect of fibromyalgia (FM) treatment on mastalgia by performing fibromyalgia screening in patients who applied for mastalgia and whose underlying cause could not be found. METHODS: Patients who applied to Kocaeli University General Surgery Outpatient Clinic between November 2017 and November 2020 with breast pain were included (n=120). Patients without cancer, systemic disease, previous breast surgery, and breast mass larger than 3 cm (n=30) were referred to the Physical Therapy and Rehabilitation Outpatient Clinic. A total of 13 patients (43%) were diagnosed with FMS. Twelve of them were given selective serotonin-noradrenaline reuptake inhibitor (duloxetine) treatment for 3 months. Turkish version of the Short Form - 36 (SF-36) quality of life scores, Visual Analog Scale (VAS), Cardiff breast pain score before and after treatment were compared. The remaining 17 patients were followed as only mastalgia. RESULTS: Patients with fibromyalgia and mastalgia had similar demographic results. At the end of the 3rd month, the complaints of breast pain completely regressed in all of the patients. Statistically significant changes were detected in VAS score, the number of trigger points, and SF-36 quality of life scores, Cardiff breast pain score after duloxetine treatment. CONCLUSION: In the presence of unexplained mastalgia, fibromyalgia should be kept in mind. Duloxetine treatment improved the breast pain and quality of life in patients with mastalgia and fibromyalgia.

A Cross-Sectional Survey Study of Cannabis Use for Fibromyalgia Symptom Management.

OBJECTIVE: To assess the use of cannabis as a symptom management strategy for patients with fibromyalgia. PATIENTS AND METHODS: An electronic, cross-sectional survey was conducted among patients diagnosed with fibromyalgia and treated in Integrative Medicine & Health at Mayo Clinic, Rochester, Minnesota. The survey was constructed with the Symptom Management Theory tool and was sent anonymously via web-based software to patients with a diagnosis of fibromyalgia. RESULTS: Of 5234 patients with fibromyalgia sent the online survey, 1336 (25.5%) responded and met the inclusion criteria. Survey respondents had a median age of 48 (Q1-Q3: 37.5-58.0) years, and most identified as female. Nearly half of respondents (49.5%, n=661) reported cannabis use since their fibromyalgia diagnosis. The most common symptoms for which respondents reported using cannabis were pain (98.9%, n=654); fatigue (96.2%; n=636); stress, anxiety, or depression (93.9%; n=621); and insomnia (93.6%; n=619). Improvement in pain symptoms with cannabis use was reported by 82.0% (n=536). Most cannabis-using respondents reported that cannabis also improved symptoms of stress, anxiety, and depression and of insomnia. CONCLUSION: Considering that cannabis is a popular choice among patients for managing fibromyalgia symptoms, clinicians should have adequate knowledge of cannabis when discussing therapeutic options for fibromyalgia with their patients.

A patient with Fibromyalgia and Chronic Recurrent Multifocal Osteomyelitis: the importance of psychosomatic assessment.

Background: Many patients affected by FM present different comorbidities, but to date no case of FM in patients with CRMO has been reported in literature. Several studies show the importance of psychosomatic assessment in FM, but only one reported the presence of allostatic overload. Case presentation: In April 2022, a 21-year-old female patient, a third-year medical student, came to our clinic to be assessed and treated for FM. She presents with a diagnosis of CRMO made in 2014 and a diagnosis of FM made in 2019. Results: At the psychiatric evaluation she presented symptoms of anxiety, depression, insomnia and reported widespread pain with the presence of almost daily headaches. From the psychosomatic point of view using DCPR-revised she presented diagnostic criteria for allostatic overload, related to study and periodic flare-ups of painful symptoms due to CRMO, persistent somatization, with musculoskeletal and gastroenterological symptoms, demoralization and type A behaviour. Conclusion: This case shows how useful a psychosomatic assessment of the patient can be for offering insights into what stressors at the origin of allostatic overload may be present in different FM patients.

Online Questionnaire with Fibromyalgia Patients Shows Negative Correlations between Disease Severity and Adherence to Mediterranean Diet.

Fibromyalgia (FM) is a multidimensional disorder in which intense chronic pain is accompanied by a variety of psychophysical symptoms that impose a burden on the patients' quality of life. Despite the efforts and the recent advancement in research, FM pathogenesis and effective treatment remain unknown. Recently, the possible role of dietary patterns and/or components has been gaining attention. The current study aimed to investigate a potential correlation between adherence to the Mediterranean diet (MedDiet) and FM severity in a sample of Italian FM patients. An online survey was designed, composed of customized questions and validated questionnaires with the aim of investigating the intensity and type of pain, the presence of other psychophysical symptoms, the overall impact of FM, general food and lifestyle habits, and adherence to the MedDiet. The collected responses were analyzed for descriptive statistics, linear regression, and propensity score analyses. The results show that, despite considerable use of pharmaceuticals and supplements, FM participants suffered from a high-severity grade disease. However, those with good adherence to the MedDiet experienced a lower pain intensity and overall FM impact. A propensity score analysis indicates a positive influence of the MedDiet against FM severity, thus unveiling the need for well-designed intervention studies to evaluate the therapeutic potential of different dietary patterns.

Healthcare experiences of fibromyalgia patients and their associations with satisfaction and pain relief. A patient survey.

OBJECTIVES: The etiology of fibromyalgia (FM) is disputed, and there is no established cure. Quantitative data on how this may affect patients' healthcare experiences are scarce. The present study aims to investigate FM patients' pain-related healthcare experiences and explore factors associated with high satisfaction and pain relief. METHODS: An anonymous, online, and patient-administered survey was developed and distributed to members of the Norwegian Fibromyalgia Association. It addressed their pain-related healthcare experiences from both primary and specialist care. Odds ratios for healthcare satisfaction and pain relief were estimated by binary logistic regression. Directed acyclic graphs guided the multivariable analyses. RESULTS: The patients (n = 1,626, mean age: 51 years) were primarily women (95%) with a 21.8-year mean pain duration and 12.7 years in pain before diagnosis. One-third did not understand why they had pain, and 56.6% did not know how to get better. More than half had not received satisfactory information on their pain cause from a physician, and guidance on how to improve was reported below medium. Patients regretted a lack of medical specialized competence on muscle pain and reported many unmet needs, including regular follow-up and pain assessment. Physician-mediated pain relief was low, and guideline adherence was deficient. Only 14.8% were satisfied with non-physician health providers evaluating and treating their pain, and 21.5% were satisfied (46.9% dissatisfied) with their global pain-related healthcare. Patients' knowledge of their condition, physicians' pain competence and provision of information and guidance, agreement in explanations and advice, and the absence of unmet needs significantly increased the odds of both healthcare satisfaction and pain relief. CONCLUSIONS: Our survey describes deficiencies in FM patients' pain-related healthcare and suggests areas for improvement to increase healthcare satisfaction and pain relief. (REC# 2019/845, 09.05.19).

Satellite Glial Cells in Human Disease.

Satellite glial cells (SGCs) are the main type of glial cells in sensory ganglia. Animal studies have shown that these cells play essential roles in both normal and disease states. In a large number of pain models, SGCs were activated and contributed to the pain behavior. Much less is known about SGCs in humans, but there is emerging recognition that SGCs in humans are altered in a variety of clinical states. The available data show that human SGCs share some essential features with SGCs in rodents, but many differences do exist. SGCs in DRG from patients suffering from common painful diseases, such as rheumatoid arthritis and fibromyalgia, may contribute to the pain phenotype. It was found that immunoglobulins G (IgG) from fibromyalgia patients can induce pain-like behavior in mice. Moreover, these IgGs bind preferentially to SGCs and activate them, which can sensitize the sensory neurons, causing nociception. In other human diseases, the evidence is not as direct as in fibromyalgia, but it has been found that an antibody from a patient with rheumatoid arthritis binds to mouse SGCs, which leads to the release of pronociceptive factors from them. Herpes zoster is another painful disease, and it appears that the zoster virus resides in SGCs, which acquire an abnormal morphology and may participate in the infection and pain generation. More work needs to be undertaken on SGCs in humans, and this review points to several promising avenues for better understanding disease mechanisms and developing effective pain therapies.

Severe fibromyalgia alleviated by the unique muscle relaxation method of applying low force: A case report.

RATIONALE: Fibromyalgia (FM) is characterized by idiopathic persistent chronic pain in the ligaments or musculoskeletal system, and more than half of the patients with FM might have migraine headaches. Direct musculoskeletal intervention could be a non-pharmacological management to relieve symptoms. However, patients with severe FM often have intense pain from only a soft touch, thereby rendering musculoskeletal intervention challenging. PATIENT CONCERNS: A 47-year-old man had progressing intense pain, and this affected his everyday life. There were no abnormal physical findings on laboratory examination such as levels of complement, antinuclear antibodies, and C-reactive protein, which were within normal limits. Magnetic resonance imaging did not indicate abnormalities. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: The patient satisfied the American College of Rheumatology criteria. Finally, we made a final diagnosis of fibromyalgia. The therapeutic intervention of Kanshoho, the unique muscle relaxation technique with low force, relieved his pain. LESSONS: If Kanshoho is carefully applied in a state of hospitalization under surveillance by an experienced physician, it could be a promising muscle relaxation method. Relaxing the trapezius muscle and reducing its intramuscular pressure might be key in treating patients with severe FM. However, it needs elucidation of its mechanism.

Rheumatology: What You May Have Missed in 2023.

Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published in 2023 that offer valuable insights for internal medicine specialists and subspecialists outside of rheumatology. The first study investigated the effect of low-dose glucocorticoids on patients with rheumatoid arthritis (RA) over 2 years and challenged existing perceptions about the risks of glucocorticoids in this setting. The second study focused on the updated guideline for preventing and treating glucocorticoid-induced osteoporosis. With the chronic and widespread use of glucocorticoids, the American College of Rheumatology emphasized the importance of assessing fracture risk and initiating pharmacologic therapy when appropriate. The third study explored the potential use of methotrexate in treating inflammatory hand osteoarthritis, suggesting a novel approach to managing this challenging and common condition. The results of the fourth article we highlight suggest that sarilumab has promise as an adjunct treatment of polymyalgia rheumatica relapse during glucocorticoid dosage tapering. The fifth study evaluated sublingual cyclobenzaprine for fibromyalgia treatment, noting both potential benefits and risks. Finally, the sixth article is a systematic review and meta-analysis that assessed the therapeutic equivalence of biosimilars and reference biologics in the treatment of patients with RA. Knowledge of this recent literature will be useful to clinicians regardless of specialty who care for patients with these commonly encountered conditions.

The role of lifestyle factors in the association between education and self-reported fibromyalgia: a mediation analysis.

BACKGROUND: Socioeconomic status as measured by education, income, or occupation, has been associated with fibromyalgia but the underlying mechanism and the role of lifestyle factors are unclear. Thus, we examine the role of modifiable lifestyle factors (body mass index, physical activity, alcohol consumption and smoking) in the association between education and self-reported fibromyalgia. METHODS: We used data from 74,157 participants in the population-based prospective Norwegian Women and Cancer (NOWAC) study. Socioeconomic position, operationalized as years of educational attainment, and lifestyle factors were assessed via self-reported questionnaires. Multiple mediation analysis was used to decompose total effects into direct and indirect effects. Estimates were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The cumulative incidence of fibromyalgia was 3.2% after a median follow up time of 13 years. Fibromyalgia was inversely associated with years of educational attainment for ≤ 9 years (HR = 2.56; 95% CI 2.32-2.91) and for 10-12 years (HR = 1.84; 95% CI 1.72-2.02), compared with ≥ 13 years of education. Overall, all lifestyle factors together jointly mediated 17.3% (95% CI 14.3-21.6) and 14.1% (95% CI 11.3-18.9) of the total effect for ≤ 9 years and 10-12 years of education, respectively. Smoking and alcohol consumption contributed the most to the proportion mediated, for ≤ 9 years (5.0% and 7.0%) and 10-12 years (5.6% and 4.5%) of education. CONCLUSION: The association between education and self-reported fibromyalgia was partly explained through lifestyle factors, mainly smoking and alcohol consumption.