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Björn Gerdle,1,2 Olof Dahlqvist Leinhard,2– 4 Eva Lund,3 Ann Bengtsson,1 Peter Lundberg,2,3 Bijar Ghafouri,1 Mikael Fredrik Forsgren2– 4 1Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, SE 581 83, Sweden; 2Centre for Medical Image Science and Visualization (CMIV), Linköping, SE 581 83, Sweden; 3Department of Radiation Physics, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, SE 581 83, Sweden; 4AMRA Medical AB, Linköping, SwedenCorrespondence: Björn Gerdle, Tel +46763927191, Email bjorn.gerdle@liu.seBackground: Obesity is a risk factor for the development of fibromyalgia (FM) and generally most studies report increased Body Mass Index (BMI) in FM. Obesity in FM is associated with a worse clinical presentation. FM patients have low physical conditioning and obesity further exacerbates these aspects. Hitherto studies of FM have focused upon a surrogate for overall measure of fat content, ie, BMI. This study is motivated by that ectopic fat and adipose tissues are rarely investigated in FM including their relationships to physical capacity variables. Moreover, their relationships to clinical variables including are not known. Aims were to 1) compare body composition between FM and healthy controls and 2) investigate if significant associations exist between body composition and physical capacity aspects and important clinical variables.Methods: FM patients (n = 32) and healthy controls (CON; n = 30) underwent a clinical examination that included pressure pain thresholds and physical tests. They completed a health questionnaire and participated in whole-body magnetic resonance imaging (MRI) to determine body composition aspects.Results: Abdominal adipose tissues, muscle fat, and BMI were significantly higher in FM, whereas muscle volumes of quadriceps were smaller. Physical capacity variables correlated negatively with body composition variables in FM. Both body composition and physical capacity variables were significant regressors of group belonging; the physical capacity variables alone showed stronger relationships with group membership. A mix of body composition variables and physical capacity variables were significant regressors of pain intensity and impact in FM. Body composition variables were the strongest regressors of blood pressures, which were increased in FM.Conclusion: Obesity has a negative influence on FM symptomatology and increases the risk for other serious conditions. Hence, obesity, dietary habits, and physical activity should be considered when developing clinical management plans for patients with FM.Keywords: body mass index, chronic pain, fibromyalgia, physical fitness, muscle, fat, magnetic resonance imaging, body composition

In fibromyalgia (FM) muscle metabolism, studies are sparse and conflicting associations have been found between muscle metabolism and pain aspects. This study compared alterations in metabolic substances and blood flow in erector spinae and trapezius of FM patients and healthy controls. FM patients (n = 33) and healthy controls (n = 31) underwent a clinical examination that included pressure pain thresholds and physical tests, completion of a health questionnaire, participation in microdialysis investigations of the etrapezius and erector spinae muscles, and also underwent phosphorus-31 magnetic resonance spectroscopy of the erector spinae muscle. At the baseline, FM had significantly higher levels of pyruvate in both muscles. Significantly lower concentrations of phosphocreatine (PCr) and nucleotide triphosphate (mainly adenosine triphosphate) in erector spinae were found in FM. Blood flow in erector spinae was significantly lower in FM. Significant associations between metabolic variables and pain aspects (pain intensity and pressure pain threshold PPT) were found in FM. Our results suggest that FM has mitochondrial dysfunction, although it is unclear whether inactivity, obesity, aging, and pain are causes of, the results of, or coincidental to the mitochondrial dysfunction. The significant regressions of pain intensity and PPT in FM agree with other studies reporting associations between peripheral biological factors and pain aspects. Funding Agencies|Swedish Research CouncilSwedish Research Council [2018-02470]; County Council of Ostergotland (Research-ALF) [LIO-700931]

BACKGROUND AND METHODS:Fibromyalgia (FMS) has a prevalence of approximately 2% in the population. Central alterations have been described in FMS, but there is not consensus with respect to the role ...

To investigate mechanisms underlying the reduced work capacity of fibromyalgia (FM) patients were compared to healthy controls at specified workloads, using P-31 magnetic resonance spectroscopy (MRS).The forearm flexor muscle group was examined with MRS at rest, at sub maximal and at maximal controlled dynamic work as well as at maximal isometric contraction. Aerobic fitness was determined by bicycle ergonometry.Metabolite concentrations and muscle pH were similar for patients and controls at lower workloads. At maximal dynamic and static contractions the concentration of inorganic phosphate was lower and at static contractions the pH decrease was smaller in patients. The performed work by patients was only 50% compared to controls and the patients experienced more pain. Maximal oxygen uptake was lower in the fibromyalgia group. Expired gas-analysis in this group showed ventilatory equivalents at similar relative levels of maximal work capacity.Fibromyalgia patients seem to utilise less of the energy rich phosphorous metabolites at maximal work despite pH reduction. They seemed to be less aerobic fitted and reached the anaerobic threshold earlier than the controls.

Objectives: To compare detection and pain thresholds in the skin of female fibromyalgia patients who were either ketamine responders or ketamine nonresponders.Methods: Detection thresholds to innocuous warmth, of cold, heat or cold pain, and touch and dynamic touch sensation were determined in the skin. Pressure pain thresholds, local and widespread pain intensity, and pain duration were also registered.Results: Ketamine nonresponse was associated with more pronounced hypersensitivity for thermal pain [especially cold pain] than ketamine response.Conclusions: Blockade of N-metyl-D-aspartic acid receptors by ketamine and the recording of pain thresholds in the skin, especially for cold pain, might reveal different mechanisms of allodynia.

Objectives: To evaluate the effect of the Feldenkrais intervention, in fibromyalgia patients.Methods: Twenty fibromyalgia patients started Feldenkrais intervention done as one individual and two group sessions weekly for 15 weeks. Nineteen started a group-based pain education program followed by a pool program. Test and self-report questionnaires were administered at the start, at six month follow up, and at the end of intervention.Results: After the Feldenkrais intervention improvement in balance and trends to better lower extremity muscle function were shown, but the improvements were not maintained.Conclusions: No sustained benefit of the Feldenkrais intervention compared to a pool program was seen. Methodological problems are discussed.

Objective: To investigate stable personality traits in 73 patients with fibromyalgia [FMS] and compare the results with healthy controls, and patients with rheumatoid arthritis [RA].Methods: Personality traits were assessed by means of the Karolinska Scales of Personality.Results: Fibromyalgia patients had significantly higher scores on the scales for somatic anxiety, muscular tension, and psychasthenia compared to patients with RA and healthy controls. Scores for psychic anxiety was in the same range in both patient groups, and was significantly lower in FMS patients compared to normals. Despite the considerable variation, as concerns duration of illness in the FMS patients, only the psychasthenia scale correlated significantly with duration of illness.Conclusion: Fibromyalgia patients are characterized by high anxiety proneness associated with autonomic symptoms, difficulties in relaxing and easily fatigued. High scores in somatic anxiety and low psychic anxiety might indicate difficulties in relaxing a...

To evaluate the subjective and objective response to intravenous regional administration of a glucocorticoid (IVRAG) on rheumatoid arthritis (RA), twenty RA-patients received, in a randomised, double-blind crossover and placebo-controlled fashion, either 50 mg methylprednisolone in mepivacaine 0.25% or mepivacaine (placebo) in one hand only using a Bier-block technique. The other hand was given the opposite. One week later the procedure was repeated but the previous placebo hand was now treated with the glucocorticoid. About 50% of the patients experienced a subjective improvement at 1 and 6 weeks. After one week a significant reduction was recorded in grip diastasis with no difference between the glucocorticoid and the placebo. In the other outcome measures (grip strength, handvolume, rest pain, and movement provoked pain) no differences were recorded between the glucocorticoid and placebo. At six weeks a significant reduction in grip diastasis and movement provoked pain as well as a significant increase in grip strength were noted. Hand volume was unchanged. IVRAG is a safe, easy and well-tolerated technique. The beneficial results are probably due to both a systemic and a regional effect. The findings of benefit in both hands at the end of one week seem to suggest that mepivacaine can give some short term improvement.

Objective: To better understand some of the pathophysiological mechanisms of chronic muscle pain. Methods: Muscle biopsies were obtained from myalgic areas in the trapezius muscle of female patients suffering from either chronic trapezius myalgia or fibromyalgia and from corresponding areas in healthy, symptom-free subjects. Electron microscopy and morphometric analysis were used to determine mean myofibrillar mitochondrial density and the capillary structure. Results: The mitochondrial fraction was higher in the patients with chronic trapezius myalgia than in those with fibromyalgia or in the healthy subjects. The mean volume density of mitochondria in the trapezius muscle fibers, however, was lower than that previously reported for human female limb muscle in all three groups. This indicates that the trapezius muscle in general has a lower capacity to tolerate endurance work than limb muscles. The morphometric analysis of the capillary structure revealed that the area and thickness of the endothelium wa...

Objectives: To reveal possible changes in muscle structure related to chronic myalgia. Methods: Muscle biopsies from tender areas of the trapezius muscle, and from corresponding areas of healthy su...

The influence of chronic pain on daily life was studied in 58 patients (55 women and three men) with fibromyalgia. The mean age was 45 +/- 11 (SD) years. A mail questionnaire including a 2-day diary was used for data collection. Information was gathered on social background, employment status, symptoms, physical training habits, patients' experience of general health, physical condition, and difficulties in performing motor tasks. The patient reported every half hour in the activity diary the degree of pain and fatigue, whether the activities were difficult to perform, and whether the patient considered them to be enjoyable, valuable, and meaningful. Fifty-five percent of the group had gainful employment. Most were working shorter hours and with changed work tasks. Motor tasks, such as carrying, holding, and running were more difficult to perform than before the onset of the symptoms, and half of the group reported most of their activities as strenuous to perform. Thirty-nine persons (67%) reported no, or very short, pain-free periods during the 2 days. In conclusion, symptoms influenced daily life considerably, and almost all patients reported changes in habits and routines as a consequence of fibromyalgia. An assessment of the patient's total life situation gives valuable information for understanding the patients' ability to handle everyday life.

Clinical course, serological response and effect of antibiotic treatment were evaluated in 34 patients with uncomplicated enterocolitis and in 27 patients with reactive arthritis (ReA) due to Yersinia enterocolitica. Patients participating in this prospective multicentre trial were randomised to treatment or no treatment with antibiotics. Only 3 (11%) of the patients who later developed ReA asked for medical care because of intestinal symptoms and fever and they all developed arthritis within 2 days after admission to hospital, i.e. before an etiological diagnosis was obtained. Patients with ReA had a history of milder intestinal symptoms than patients with uncomplicated enterocolitis. The peak IgA titer to Y. enterocolitica, as measured by enzyme linked immunosorbent assay, was higher in ReA patients and it was not affected by the presence of HLA-B27 antigen. On the other hand, untreated patients with uncomplicated enterocolitis had the longest duration of IgG antibodies. The duration of IgG antibody response was shortened in uncomplicated enterocolitis patients treated with antibiotics, but not in ReA patients. Treatment did not influence intestinal or ReA symptoms. It is concluded, that patients with uncomplicated enterocolitis due to Y. enterocolitica differ in intestinal symptoms and serological response, compared with patients who develop ReA. These parameters could however not be used to predict the development of arthritis in individual patients.

Fibromyalgia is currently classified as chronic widespread pain with widespread allodynia to pressure pain. There are few data describing pain characteristics, quality of life, consequences for daily living, and psychosocial status in patients who meet the classification criteria for fibromyalgia proposed by the American College of Rheumatology compared with patients with chronic widespread pain but not widespread allodynia. This study used a randomly selected sample from the general population. A postal questionnaire and a pain mannequin were sent to 9952 people. The response rate was 76.7%. The pain drawings showed that 345 people had widespread pain; that is, they noted pain in all four extremities and axially. Clinical examination, which included a manual tender point examination, was performed in 125 subjects. These people answered commonly used questionnaires on pain, quality of life, coping strategies, depression, and anxiety. Compared with chronic widespread pain without widespread allodynia, fibromyalgia was associated with more severe symptoms/consequences for daily life and higher pain severity. Similar coping strategies were found. Chronic widespread pain without widespread allodynia to pressure pain was found in 4.5% in the population and fibromyalgia in 2.5%.

To investigate the prevalence of current and chronic pain and their relationship to pain intensity, sex, age, income, employment status, citizenship, marital status, urban residence, occupational activity, and healthcare-seeking based on a representative sample from a Swedish county.A cross-sectional survey using a postal questionnaire was sent to a representative sample (n = 9952) of the target population (284,073 people, age 18-74 yrs) in a county (Ostergötland) in southern Sweden. A questionnaire was mailed and followed by 2 postal reminders if necessary.The participation rate was 76.7% (n = 7637); nonparticipants were on average younger, male, and earned less money. The overall point prevalence of pain was 48.9%. The corresponding one-month period prevalence was 63.0%, and pain on several occasions during the previous 3 months was reported by 61.3% of participants. The prevalence of chronic pain (pain3 months) was 53.7%. Female sex, age, and sick leave/early retirement were generally of significant importance in the regressions of pain. No sex factor was found in the regressions of pain frequency and pain intensity. Chronic pain especially frequent and intensive pain showed clear associations with healthcare-seeking and occupational activity.High prevalence of current pain (48.9%) and chronic pain (53.7%) were found in this community-based study. Being female, older, and on sick leave or early retirement were generally of significant importance in the regressions of pain. Chronic pain showed clear associations with healthcare-seeking and occupational activity, indicating considerable socioeconomic costs.

Although muscle pain is common in primary Sjögren's syndrome (SS), the underlying mechanisms are mainly unknown. We studied all patients with SS at our rheumatology unit with respect to muscle pain in general and to fibromyalgia (FM), and correlated clinical data to muscle biopsy findings.We investigated 48 patients with SS according to the modified European diagnostic criteria. The ACR criteria for FM were used to subgroup the patients. Muscle biopsy was performed in 36 patients. Light microscope morphology and immunohistochemical expression of MHC class I, MHC class II, and membrane attack complex (MAC) were studied.We found 44% of patients complained of muscle pain; 27% fulfilled the ACR criteria for FM, whereas 17% had other forms of myalgia. Muscle pain could not be related to histopathological findings. Signs of inflammation were found in 26 of 36 biopsies (72%), and inflammation combined with degeneration/regeneration (i.e., histological signs of polymyositis) in 17 biopsies (47%). However, only 5 patients (14%) had clinical as well as histological signs of polymyositis. Eight muscle biopsies (22%) showed histological features of inclusion body myositis (IBM). However, no patient had clinical symptoms suggestive of this disease. Abnormal expression of MHC class I, MHC class II, and MAC was found in 18 (50%), 16 (44%), and 27 (75%) patients, respectively.Muscle pain, especially FM, is common in SS. Histopathological signs of myositis are very common in SS. However, muscle symptoms are not related to histological signs of muscle inflammation. IBM-like findings may represent vacuolar myopathic degeneration due to previous subclinical muscle inflammation rather than a specific clinical entity.

The intestinal permeability to polyethyleneglycols (PEGs) of varying size in patients with rheumatoid arthritis has been investigated. Permeability was determined by measuring the 6-hour urinary recovery of different-sized PEGs after oral intake of PEG 400, PEG 1000, or PEG 3000. Patients with rheumatoid arthritis excreted significantly less PEG 400 and PEG 1000 than healthy individuals, whereas the excretion of PEG 3000 was the same or even greater than in healthy individuals. These findings point to the possibility that intestinal permeability is altered in rheumatoid arthritis.

The clinical symptoms of 55 patients with primary fibromyalgia (PF) were studied and compared with 30 patients with rheumatoid arthritis (RA). The PF patients expressed a more intense feeling of illness than did the RA patients. Stiffness occurred just as often in PF as in RA. Trigger points occurred less frequently in RA patients. Muscular fatigue appeared to be one of the most disabling symptoms in PF. Neurophysiological studies indicated that the fatigue was at least partly of central origin. Ischemic forearm exercise test gave no evidence of impaired glycogenolysis. Laboratory investigation revealed normal 25-hydroxyvitamin D, cobalamin, folate, estrogen, testosterone, and myoglobin in the PF patients.

The lymphocyte-stimulating capacity of bacterial antigens from Yersinia enterocolitica and Chlamydia trachomaris was studied in 14 patients with Reiter's syndrome and compared with 16 healthy controls. The influence of HLA-B27 was evaluated. There was an increased reactivity in patients compared with controls. The most pronounced reactivity was seen in HLA-B27-positive patients. These findings support the hypothesis that there is an impaired T-cell function in HLA-B27-associated diseases.

Extensive bacteriological testing was performed in 25 patients with complete or incomplete Reiter's syndrome. In 21 patients (84%), evidence of antecedent infection was found, based on culture and/or serological findings. Thus, infection with Chlamydia trachomatis (17 patients), Yersinia enterocolitica, serotype 3 (4 patients), and Campylobacter jejuni (1 patient) was identified.

Muscle energy metabolism was studied by chemical analysis of biopsy samples from: 1) trigger points in the trapezius muscle from 15 patients with primary fibromyalgia (PF), 2) nonpainful, anterior tibial muscle from 6 patients with PF, and 3) the trapezius muscle from 8 healthy controls. We found a decrease in the levels of adenosine triphosphate, adenosine diphosphate, and phosphoryl creatine, and an increase in the levels of adenosine monophosphate and creatine, in the trapezius muscles from the patients. These findings support the notion that the pain in patients with PF is of muscular origin.

Seventy-seven muscle biopsies from 57 patients with primary fibromyalgia and 17 biopsies from 9 healthy controls were examined by routine histopathological and histochemical methods. All patients fulfilled strict diagnostic criteria. 42 biopsies from patients were deemed normal or borderline, while 35 showed discrete pathological changes (degeneration, regeneration, inflammatory infiltrates, ragged red fibres, and 'moth-eaten' fibres in muscles other than m. trapezius). Biopsies from controls were normal or borderline in 14 and showed mild focal abnormalites in 3 cases. 'Moth-eaten' fibres were found in 35 of 41 trapezius biopsies taken from patients and in 9 of 10 trapezius biopsies from controls. Ragged red fibres were found in 15 of 41 trapezius biopsies taken from patients. In the deltoid muscle, 'moth-eaten' fibres were found in 3 and ragged red fibres in 2 of 9 biopsies from patients. Frequency of type I and type II fibres and the area of muscle fibres were the same in patients as in controls. Capillary density was the same in both groups. These changes, although not sufficient to constitute a diagnostic test for PF, indicate that this condition has an organic basis.

Nine patients with primary fibromyalgia participated. The patients were studied prior to, during and immediately after 4 identical periods of exercise (bicycle ergometer) each performed 30 min after injection with saline, repeated saline, an opioid and naloxone. All substances were given epidurally, except for naloxone which was given intravenously. Finally, with the patients resting in bed, lignocaine was injected epidurally. Physiological variables, general exertion, dyspnoea, lower extremity exhaustion, pain and tender points in the lower half of the body were examined. Resting pain and tender points diminished significantly after the opioid injection. Lignocaine completely abolished resting pain and tender points. Lower extremity exhaustion was reduced by the opioid. General exertion and dyspnoea were unaffected by the opioid. In conclusion the results support the hypothesis that the pain in fibromyalgia is of peripheral nociceptive or spinal origin. We raise the hypothesis that the fatigability is, at least partly, due to inhibition because of pain.

Muscle biopsies from the descending portion of the trapezius muscle were studied in 9 healthy subjects and in 10 patients with localized chronic myalgia related to static load during repetitive assembly work for 16 (10-31) years, with 10 (4-26) months of sick leave at the time of biopsy. Both categories showed isolated atrophic muscle fibers and occasional abnormal fibers with internally situated nuclei, some variation in fiber diameter, and fiber splitting. Fibers with a "moth-eaten" appearance due to a multifocal loss of oxidative enzyme activity were frequent both in the healthy and in the myalgic individuals. In contrast, isolated pathologic "ragged red" fibers were only found in the cases with myalgia (8 of 10), strongly suggesting mitochondrial damage. The phenomenon was confined to the Type 1 fibers. The frequency of Type 1 fibers was increased. Levels of adenosine triphosphate and adenosine diphosphate were reduced in myalgia patients, whereas lactate, pyruvate, and glycogen levels were normal, as well as phosphoryl creatine and total creatine.

Background This population study based on a representative sample from a Swedish county investigates the prevalence, duration, and determinants of widespread pain (WSP) in the population using two constructs and estimates how WSP affects work status. In addition, this study investigates the prevalence of widespread pain and its relationship to pain intensity, gender, age, income, work status, citizenship, civil status, urban residence, and health care seeking. Methods A cross-sectional survey using a postal questionnaire was sent to a representative sample (n = 9952) of the target population (284,073 people, 18–74 years) in a county (Östergötland) in the southern Sweden. The questionnaire was mailed and followed by two postal reminders when necessary. Results The participation rate was 76.7% (n = 7637); the non-participants were on the average younger, earned less money, and male. Women had higher prevalences of pain in 10 different predetermined anatomical regions. WSP was generally chronic (90–94%) and depending on definition of WSP the prevalence varied between 4.8–7.4% in the population. Women had significantly higher prevalence of WSP than men and the age effect appeared to be stronger in women than in men. WSP was a significant negative factor – together with age 50–64 years, low annual income, and non-Nordic citizen – for work status in the community and in the group with chronic pain. Chronic pain but not the spreading of pain was related to health care seeking in the population. Conclusion This study confirms earlier studies that report high prevalences of widespread pain in the population and especially among females and with increasing age. Widespread pain is associated with prominent effects on work status.

A 36-year-old HLA B 27 positive woman developed reactive type arthritis a week after enterocolitis. Stool culture and serological tests indicated Campylobacter jejuni infection. Serological evidence of previous Chlamydial infection was also obtained. The arthritis ran a benign course of 6 months, leaving no residual symptoms.