The effects of a 15-week physical exercise intervention on pain modulation in fibromyalgia: Increased pain-related processing within the cortico-striatal- occipital networks, but no improvement of exercise-induced hypoalgesia.

Dysfunctional top-down pain modulation is a hallmark of fibromyalgia (FM) and physical exercise is a cornerstone in FM treatment. The aim of this study was to explore the effects of a 15-week intervention of strengthening exercises, twice per week, supervised by a physiotherapist, on exercise-induced hypoalgesia (EIH) and cerebral pain processing in FM patients and healthy controls (HC). FM patients (n = 59) and HC (n = 39) who completed the exercise intervention as part of a multicenter study were examined at baseline and following the intervention. Following the exercise intervention, FM patients reported a reduction of pain intensity, fibromyalgia severity and depression. Reduced EIH was seen in FM patients compared to HC at baseline and no improvement of EIH was seen following the 15-week resistance exercise intervention in either group. Furthermore, a subsample (Stockholm site: FM n = 18; HC n = 19) was also examined with functional magnetic resonance imaging (fMRI) during subjectively calibrated thumbnail pressure pain stimulations at baseline and following intervention. A significant main effect of exercise (post > pre) was observed both in FM patients and HC, in pain-related brain activation within left dorsolateral prefrontal cortex and caudate, as well as increased functional connectivity between caudate and occipital lobe bordering cerebellum (driven by the FM patients). In conclusion, the results indicate that 15-week resistance exercise affect pain-related processing within the cortico-striatal-occipital networks (involved in motor control and cognition), rather than directly influencing top-down descending pain inhibition. In alignment with this, exercise-induced hypoalgesia remained unaltered.

Pain Burden in Post-COVID-19 Syndrome following Mild COVID-19 Infection.

The global pandemic of SARS-CoV-2 has affected several hundred million people, and many infected people have suffered from a milder initial infection but have never fully recovered. This observational study investigates the pain burden in sufferers of post-COVID-19 syndrome after a milder initial infection. One hundred post-COVID-19 patients filled out questionnaires regarding sociodemographic data, previous comorbidities, present pharmacological treatment, pain intensity and pain localisation. Health-related quality of life, fatigue, emotional status, and insomnia were measured by validated questionnaires. Multiple post-COVID-19 symptoms, including post-exertional malaise, were evaluated by a symptom questionnaire. Among the 100 participants (mean age 44.5 years), 82% were women, 61% had higher education, and 56% were working full or part time. Nine participants reported previous pain or inflammatory conditions. Among the most painful sites were the head/face, chest, lower extremities, and migrating sites. Generalised pain was self-reported by 75 participants and was estimated in 50 participants. Diagnosis of fibromyalgia according to the 2016 criteria was suspected in 40 participants. Subgroup analyses indicated that comorbidities might play a role in the development of pain. In conclusion, a major part of sufferers from post-COVID-19 syndrome develop pain, and in addition to its many disabling symptoms, there is an urgent need for pain management in post-COVID-19 syndrome.

Distinct aberrations in cerebral pain processing differentiating patients with fibromyalgia from patients with rheumatoid arthritis.

ABSTRACT: The current study used functional magnetic resonance imaging to directly compare disease-relevant cerebral pain processing in well-characterized patient cohorts of fibromyalgia (FM, nociplastic pain) and rheumatoid arthritis (RA, nociceptive pain). Secondary aims were to identify pain-related cerebral alterations related to the severity of clinical symptoms such as pain intensity, depression, and anxiety. Twenty-six patients with FM (without RA-comorbidity) and 31 patients with RA (without FM-comorbidity) underwent functional magnetic resonance imaging while stimulated with subjectively calibrated painful pressures corresponding to a pain sensation of 50 mm on a 100-mm visual analogue scale. Stimulation sites were at the most inflamed proximal interphalangeal joint in the left hand in patients with RA and the left thumbnail in patients with FM, 2 sites that have previously been shown to yield the same brain activation in healthy controls. The current results revealed disease-distinct differences during pain modulation in RA and FM. Specifically, in response to painful stimulation, patients with FM compared to patients with RA exhibited increased brain activation in bilateral inferior parietal lobe (IPL), left inferior frontal gyrus (IFG)/ventrolateral prefrontal cortex (vlPFC) encapsulating left dorsolateral prefrontal cortex, and right IFG/vlPFC. However, patients with RA compared to patients with FM exhibited increased functional connectivity (during painful stimulation) between right and left IPL and sensorimotor network and between left IPL and frontoparietal network. Within the FM group only, anxiety scores positively correlated with pain-related brain activation in left dorsolateral prefrontal cortex and right IFG/vlPFC, which further highlights the complex interaction between affective (ie, anxiety scores) and sensory (ie, cerebral pain processing) dimensions in this patient group.

Internet-Administered Emotional Awareness and Expression Therapy for Somatic Symptom Disorder With Centralized Symptoms: A Preliminary Efficacy Trial.

Background: There is growing evidence that trauma, psychosocial conflict, and difficulties with emotional processing contribute to centralized somatic symptoms. Emotional Awareness and Expression Therapy (EAET) was developed to address these factors and reduce symptoms, and EAET has shown efficacy in face-to-face formats. No trial of an internet-delivered EAET (I-EAET) exists, however, so we developed such an intervention and conducted an uncontrolled feasibility and potential efficacy trial of I-EAET for patients with Somatic Symptom Disorder (SSD) with centralized symptoms (SSD-CS). Method: After screening potential participants, a sample of 52 patients (50 women, two men; age M = 49.6, SD = 11.9) diagnosed with SSD-CS initiated treatment. I-EAET consisted of nine weekly modules focused on psychoeducation, emotional awareness and exposure, and anxiety regulation with self-compassion. Therapists communicated with each patient by email for about 20 min per week during treatment, answering questions and giving feedback on homework assignments. Patients completed measures of somatic symptoms, depression, anxiety, trauma-related symptoms, and functional disability before treatment and again at post-treatment and 4-month follow-up. Results: A large reduction in somatic symptoms (PHQ-15) occurred pre-to post-treatment (d = 1.13; 95% CI: 0.84-1.47) which was fully maintained at 4-month follow-up (d = 1.19; 95% CI: 0.88-1.56). Twenty-three percent of the patients at post-treatment and 27% at follow-up achieved a 50% or greater reduction in somatic symptoms, and about 70% achieved a minimally important clinical difference. In addition, at post-treatment, there were small to medium reductions (d's from 0.33 to 0.72) in anxiety (GAD-7), depression (PHQ-9), trauma-related symptoms (PCL-5), and functional disability (Sheehan Disability Scale). For all of these secondary outcomes, improvements were slightly to substantially larger at follow-up than at post-treatment (d's from 0.46 to 0.80). Conclusion: I-EAET appears to be a feasible treatment for adults with SSD and centralized symptoms, resulting in substantial and durable improvement not only in somatic symptoms but in other psychiatric symptoms and functioning. Controlled trials are needed determine the effects of I-EAET specifically and how this approach compares to face-to-face EAET and to other internet-delivered treatments, such as cognitive-behavioral interventions. Research should also identify treatment responders and mechanisms of change in EAET. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04122846.

Preliminary ICF core set for patients with myalgic encephalomyelitis/chronic fatigue syndrome in rehabilitation medicine.

OBJECTIVE: To create and evaluate a preliminary ICF Core Set for myalgic encephalomyelitis/chronic fatigue syndrome using a team-based approach. DESIGN: Observational study. SUBJECTS/PATIENTS: A total of 100 consecutive patients (mean age 45 years (standard deviation (SD) 9 years)) were assessed by a rehabilitation team and included in the study. METHODS: A preliminary International Classification of Functioning, Disability and Health (ICF) Core Set was created, based on literature studies, and on discussion forums between the team and the researchers. Patients were assessed by a rehabilitation medicine team regarding impairments in body function, activity limitations, and restrictions in participation. RESULTS: Clinical assessments of the component Body Functions found impairments in energy, fatigue, physical endurance, fatigability, sleep and pain in 82-100% of patients. At least half of the patients had impairments in higher cognitive functions, attention, and emotions, as well as sound and light hypersensitivity, general hyper-reactivity and thermoregulatory functions. For the component Activity/Participation, the most frequent limitations and restrictions were in doing housework (93%), assisting others (92%), acquisition of goods and services (90%), remunerative employment (87%), handling stressful situations (83%), preparing food (83%), recreation and leisure (82%), informal socializing (78%) and carrying out daily activities (77%). The most frequent degrees of impairments/limitations/restrictions assessed were light and moderate, except for remuneative employment, for which restrictions were severe. CONCLUSION: Using unconventional methods, this study sets out a preliminary ICF Core Set list for patients with myalgic encephalomyelitis/chronic fatigue syndrome. Further studies are required to improve and test this Core Set in myalgic encephalomyelitis/chronic fatigue syndrome populations.

Plasma tryptophan and kynurenine in females with temporomandibular disorders and fibromyalgia-An exploratory pilot study.

BACKGROUND: Both temporomandibular disorders myalgia (TMDM) and fibromyalgia (FM) have been linked to central and peripheral changes in serotonin availability. The precursor of serotonin, tryptophan (TRP), is mainly catabolised via another pathway to produce kynurenine (KYN), but whether changes of this pathway are present in TMDM and FM are still unclear. OBJECTIVE: The aim was to explore blood plasma concentrations of TRP and KYN in TMDM and FM in an attempt to identify novel associations for future research. METHODS: Plasma of 113 female participants (17 TMDM, 40 FM and 56 healthy pain-free controls) were analysed for TRP and KYN concentrations. The degradation of TRP via the KYN pathway was indicated by the KYN to TRP ratio (KYN/TRP). Pain intensities were assessed with the Graded Chronic Pain Scale (GCPS) and Visual Analogue Scale (VAS). Psychological symptoms were evaluated using the Hospital Anxiety and Depression Scale (HADS), Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder scale (GAD-7). RESULTS: In TMDM there was a negative correlation between TRP and pain intensity (rs  = -0.55 P = .023) and positive correlations between KYN/TRP and pain intensity (rs  = 0.59 P = .013). In FM, KYN/TRP was negatively correlated with anxiety symptoms (rs  = -0.36 P = .022) and a trend towards significantly lower TRP levels was found compared to controls (P = .05). CONCLUSION: The association between KYN/TRP and pain intensity as well as anxiety ratings in this small exploratory study may indicate that KYN/TRP could be a relevant indicator for symptom severity in TMDM and FM. Further investigations of the KYN pathway in chronic myalgia are warranted.

Patients with chronic fatigue syndrome do not score higher on the autism-spectrum quotient than healthy controls: Comparison with autism spectrum disorder.

Clinically, there is an overlap of several symptoms of chronic fatigue syndrome (CFS) and autism spectrum disorder (ASD), including fatigue; brain "fog"; cognitive impairments; increased sensitivity to sound, light, and odour; increased pain and tenderness; and impaired emotional contact. Adults with CFS (n = 59) or ASD (n = 50) and healthy controls (HC; n = 53) were assessed with the Autism-Spectrum Quotient (AQ) in a cross-sectional study. Non-parametric analysis was used to compare AQ scores among the groups. Univariate analysis of variance (ANCOVA) was used to identify if age, sex, or diagnostic group influenced the differences in scores. Patients with ASD scored significantly higher on the AQ than the CFS group and the HC group. No differences in AQ scores were found between the CFS and HC groups. AQ results were influenced by the diagnostic group but not by age or sex, according to ANCOVA. Despite clinical observations of symptom overlap between ASD and CFS, adult patients with CFS report few autistic traits in the self-report instrument, the AQ. The choice of instrument to assess autistic traits may influence the results.

Sleep patterns among patients with chronic fatigue: A polysomnography-based study.

OBJECTIVES: The purpose of this study was to detect treatable sleep disorders among patients complaining of chronic fatigue by using sleep questionnaires and polysomnography. METHODS: Patients were referred to hospital for investigations and rehabilitation because of a suspected diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The criteria for further referral to full-night polysomnography (PSG) were symptoms of excessive daytime sleepiness and/or tiredness in the questionnaires. RESULTS: Of a total of 381 patients, 78 (20.5%) patients underwent PSG: 66 women and 12 men, mean age 48.6 years, standard deviation ±9.9 years. On the basis of the PSG, 31 (40.3%) patients were diagnosed with obstructive sleep apnoea, 7 (8.9%) patients with periodic limb movement disorder, 32 (41.0%) patients with restless legs syndrome and 54 (69.3%) patients had one or more other sleep disorder. All patients were grouped into those who fulfilled the diagnostic criteria for ME/CFS (n = 55, 70.5%) and those who did not (n = 23, 29.5%). The latter group had significantly higher respiratory (P = .01) and total arousal (P = .009) indexes and a higher oxygen desaturation index (P = .009). CONCLUSIONS: More than half of these chronic fatigue patients, who also have excessive daytime sleepiness and/or tiredness, were diagnosed with sleep disorders such as obstructive sleep apnoea, periodic limb movement disorder and/or restless legs syndrome. Patients with such complaints should undergo polysomnography, fill in questionnaires and be offered treatment for sleep disorders before the diagnose ME/CFS is set.

Pain and fear avoidance partially mediate change in muscle strength during resistance exercise in women with fibromyalgia.

OBJECTIVES: Resistance exercise results in health benefits in fibromyalgia. The aim of this study was to determine the factors that mediate change in muscle strength in women with fibromyalgia as a result of resistance exercise. METHODS: Sixty-seven women with fibromyalgia (age range 25-64 years) were included. Tests of muscle strength and questionnaires related to pain, fear avoidance and physical activity were carried out. Multivariable stepwise regression was used to analyse explanatory factors for change and predictors for final values of knee-extension force, elbow-flexion force and hand-grip force. RESULTS: Change in knee-extension force was explained by fear avoidance beliefs about physical activity at baseline, together with change in pain intensity, knee-extension force at baseline, age and body mass index (BMI) (R2=0.40, p = 0.013). Change in elbow-flexion force was explained by pain intensity at baseline, together with baseline fear avoidance beliefs about physical activity, BMI and elbow-flexion force at baseline (R2 = 0.32, p = 0.043). Change in hand-grip force was explained by hand-grip force at baseline, change in pain intensity and baseline fear avoidance (R2 = 0.37, p = 0.009). Final muscle strength was predicted by the same variables as change, except pain. CONCLUSION: Pain and fear avoidance are important factors to consider in rehabilitation using resistance exercise for women with fibromyalgia.

Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls-antagonistic effects between opioid and serotonin-related genes.

Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH.

Benefits of resistance exercise in lean women with fibromyalgia: involvement of IGF-1 and leptin.

BACKGROUND: Chronic pain and fatigue improves by exercise in fibromyalgia (FM) but underlying mechanisms are not known. Obesity is increased among FM patients and associates with higher levels of pain. Symptom improvement after aerobic exercise is affected by body mass index (BMI) in FM. Metabolic factors such as insulin-like growth factor 1 (IGF-1) and leptin may be involved. In this study, the aim was to evaluate the role of metabolic factors in lean, overweight and obese women during resistance exercise, in relation to symptom severity and muscle strength in women with FM. METHODS: Forty-three women participated in supervised progressive resistance exercise, twice weekly for 15-weeks. Serum free and total IGF-1, IGF-binding protein 3 (IGFBP3), adiponectin, leptin and resistin were determined at baseline and after 15-weeks. Level of current pain was rated on a visual analogue scale (0-100 mm). Level of fatigue was rated by multidimensional fatigue inventory (MFI-20) subscale general fatigue (MFIGF). Knee extension force, elbow flexion force and handgrip force were assessed by dynamometers. RESULTS: Free IGF-1 (p = 0.047), IGFBP3 (p = 0.025) and leptin (p = 0.008) were significantly decreased in lean women (n = 18), but not in the overweight (n = 17) and the obese (n = 8). Lean women with FM benefited from resistance exercise with improvements in current pain (p= 0.039, n = 18), general fatigue (MFIGF, p = 0.022, n = 18) and improved elbow-flexion force (p = 0.017, n = 18). In overweight and obese women with FM there was no significant improvement in pain or fatigue but an improvement in elbow flexion (p = 0.049; p = 0.012) after 15 weeks of resistance exercise. CONCLUSION: The clearest clinical response to resistance exercise was found in lean patients with FM. In these individuals, individualized resistance exercise was followed by changes in IGF-1 and leptin, reduced pain, fatigue and improved muscular strength. In overweight and obese women FM markers of metabolic signaling and clinical symptoms were unchanged, but strength was improved in the upper limb. Resistance exercise combined with dietary interventions might benefit patients with FM and overweight. TRIAL REGISTRATION: The trial was registered 21 of October 2010 with ClinicalTrials.gov identification number: NCT01226784 .

Differences in alexithymia and emotional awareness in exhaustion syndrome and chronic fatigue syndrome.

Symptoms of Exhaustion Syndrome (ES) and Chronic Fatigue Syndrome (CFS) are overlapping and create difficulties of differential diagnosis. Empirical studies comparing ES and CFS are scarce. This study aims to investigate if there are any emotional differences between ES and CFS. This cross-sectional study compared self-reported alexithymia and observer-rated emotional awareness in patients with ES (n = 31), CFS (n = 38) and healthy controls (HC) (n = 30). Self-reported alexithymia was measured with the Toronto Alexithymia Scale-20 (TAS-20) and emotional awareness with an observer-rated performance test, the Level of Emotional Awareness Scale (LEAS). Additionally, depression and anxiety were scored by the Hospital Anxiety and Depression Scale (HADS). Results show that patients with ES expressed higher self-reported alexithymia in the TAS-20 compared to HC, but had similar emotional awareness capacity in the observer-rated performance test, the LEAS. Patients with CFS expressed more difficulties in identifying emotions compared to HCs, and performed significantly worse in the LEAS-total and spent more time completing the LEAS as compared to HC. Correlation and multiple regressions analyses revealed that depression and anxiety positively correlated with and explained part of the variances in alexithymia scores, while age and group explained the major part of the variance in LEAS. Findings of this study indicate that emotional status is different in patients with ES and CFS with respect to both self-reported alexithymia and observer-rated emotional awareness. Emotional parameters should be approached both in clinical investigation and psychotherapy for patients with ES and CFS.

The translocator protein gene is associated with symptom severity and cerebral pain processing in fibromyalgia.

The translocator protein (TSPO) is upregulated during glia activation in chronic pain patients. TSPO constitutes the rate-limiting step in neurosteroid synthesis, thus modulating synaptic transmission. Related serotonergic mechanisms influence if pro- or anti-nociceptive neurosteroids are produced. This study investigated the effects of a functional genetic polymorphism regulating the binding affinity to the TSPO, thus affecting symptom severity and cerebral pain processing in fibromyalgia patients. Gene-to-gene interactions with a functional polymorphism of the serotonin transporter gene were assessed. Fibromyalgia patients (n=126) were genotyped regarding the polymorphisms of the TSPO (rs6971) and the serotonin transporter (5-HTTLPR/rs25531). Functional magnetic resonance imaging (n=24) was used to study brain activation during individually calibrated pressure pain. Compared to mixed/low TSPO affinity binders, the high TSPO affinity binders rated more severe pain (p=0.016) and fibromyalgia symptoms (p=0.02). A significant interaction was found between the TSPO and the serotonin transporter polymorphisms regarding pain severity (p<0.0001). Functional connectivity analyses revealed that the TSPO high affinity binding group had more pronounced pain-evoked functional connectivity in the right frontoparietal network, between the dorsolateral prefrontal area and the parietal cortex. In conclusion, fibromyalgia patients with the TSPO high affinity binding genotype reported a higher pain intensity and more severe fibromyalgia symptoms compared to mixed/low affinity binders, and this was modulated by interaction with the serotonin transporter gene. To our knowledge this is the first evidence of functional genetic polymorphisms affecting pain severity in FM and our findings are in line with proposed glia-related mechanisms. Furthermore, the functional magnetic resonance findings indicated an effect of translocator protein on the affective-motivational components of pain perception.

Resistance exercise improves physical fatigue in women with fibromyalgia: a randomized controlled trial.

BACKGROUND: Fibromyalgia (FM) affects approximately 1-3 % of the general population. Fatigue limits the work ability and social life of patients with FM. A few studies of physical exercise have included measures of fatigue in FM, indicating that exercise can decrease fatigue levels. There is limited knowledge about the effects of resistance exercise on multiple dimensions of fatigue in FM. The present study is a sub-study of a multicenter randomized controlled trial in women with FM. The purpose of the present sub-study was to examine the effects of a person-centered progressive resistance exercise program on multiple dimensions of fatigue in women with FM, and to investigate predictors of the potential change in fatigue. METHODS: A total of 130 women with FM (age 22-64 years) were included in this assessor-blinded randomized controlled multicenter trial examining the effects of person-centered progressive resistance exercise compared with an active control group. The intervention was performed twice a week for 15 weeks. Outcomes were five dimensions of fatigue measured with the Multidimensional Fatigue Inventory (MFI-20). Information about background was collected and the women also completed several health-related questionnaires. Multiple linear stepwise regression was used to analyze predictors of change in fatigue in the total population. RESULTS: A higher improvement was found at the post-treatment examination for change in the resistance exercise group, as compared to change in the active control group in the MFI-20 subscale of physical fatigue (resistance group Δ -1.7, SD 4.3, controls Δ 0.0, SD 2.7, p = 0.013), with an effect size of 0.33. Sleep efficiency was the strongest predictor of change in the MFI-20 subscale general fatigue (beta = -0.54, p = 0.031, R (2) = 0.05). Participating in resistance exercise (beta = 1.90, p = 0.010) and working fewer hours per week (beta = 0.84, p = 0.005) were independent significant predictors of change in physical fatigue (R (2) = 0.14). CONCLUSIONS: Person-centered progressive resistance exercise improved physical fatigue in women with FM when compared to an active control group. TRIAL REGISTRATION: ClinicalTrials.gov NCT01226784 . Registered 21 October 2010.

Effects of 15 weeks of resistance exercise on pro-inflammatory cytokine levels in the vastus lateralis muscle of patients with fibromyalgia.

BACKGROUND: This study aimed at investigating the effect of a resistance exercise intervention on the interstitial muscle levels of pro-inflammatory cytokines in fibromyalgia (FMS) and healthy controls (CON). METHODS: Twenty-four female patients with FMS (54 ± 8 years) and 27 female CON (54 ± 9 years) were subjected to intramuscular microdialysis of the most painful vastus lateralis muscle before and after 15 weeks of progressive resistance exercise twice per week. Baseline dialysates were sampled in the resting muscle 140 min after insertion of the microdialysis catheter. The participants then performed repetitive dynamic contractions (knee extension) for 20 min, followed by 60 min rest. Pain intensity was assessed with a 0-100 mm visual analogue scale (VAS), and fatigue was assessed with Borg's RPE throughout microdialysis. Dialysates were sampled every 20 min and analyzed with Luminex for interleukin (IL)-1ß, tumor necrosis factor (TNF) alpha, IL-6, and IL-8. RESULTS: At both sessions and for both groups the dynamic contractions increased pain (P < 0.012) and fatigue (P < 0.001). The levels of TNF were lower in the FMS group than the CON group at both sessions (P < 0.05), but none of the other cytokines differed between the groups. IL-6 and IL-8 increased after the dynamic contractions in both groups (P < 0.010), while TNF increased only in CON (P < 0.05) and IL-1ß did not change. Overall pain intensity was reduced after the 15 weeks of resistance exercise in FMS (P < 0.05), but there was no changes in fatigue or cytokine levels. CONCLUSION: Progressive resistance exercise for 15 weeks did not affect the interstitial levels of IL-1ß, TNF, IL-6, and IL-8 in the vastus lateralis muscle of FMS patients or CON. TRIAL REGISTRATION: Clinicaltrials.gov NCT01226784 , registered 21 October 2010.

Decrease of fear avoidance beliefs following person-centered progressive resistance exercise contributes to reduced pain disability in women with fibromyalgia: secondary exploratory analyses from a randomized controlled trial.

BACKGROUND: Fibromyalgia (FM) is characterized by persistent widespread pain, increased pain sensitivity and tenderness. Women with FM also report disability, in terms of negative consequences on activities of daily living. Our recent randomized controlled trial (RCT) is the first study of resistance exercise to show positive effects on pain disability. The resistance exercise program of our RCT emphasized active involvement of participants in planning and progression of the exercise, using the principles of person-centeredness, to support each participant's ability to manage the exercise and the progress of it. The aim of this sub-study was to investigate explanatory factors for reduced pain disability in women with FM participating in a 15-week person-centered progressive resistance exercise program. METHODS: A total of 67 women with FM were included in this sub-study of an RCT examining the effects of person-centered progressive resistance exercise performed twice a week for 15 weeks. Tests of physical capacity and health-related questionnaires were assessed at baseline and after the intervention period. Multivariable stepwise regression was used to analyze explanatory factors for improvements in pain disability. RESULTS: Reduced pain disability was explained by higher pain disability at baseline together with decreased fear avoidance beliefs about physical activity (R (2) = 28, p = 0.005). The improvements in the disability domains of recreation and social activity were explained by decreased fear avoidance beliefs about physical activity together with higher baseline values of each disability domain respectively (R (2) = 32, p = 0.025 and R (2) = 30, p = 0.017). The improvement in occupational disability was explained by higher baseline values of occupational disability (R (2) = 19, p = 0.001). CONCLUSION: The person-centered resistance exercise intervention, based on principles of self-efficacy, had a positive effect on recreational, social and occupational disability. The reduced pain disability seemed to be mediated by decreased fear avoidance beliefs. Age, symptom duration, pain intensity, and muscle strength at baseline had no explanatory value for reduced pain disability, indicating that the person-centered resistance exercise program has the potential to work for anyone with FM who has interest in physical exercise. The trial was registered on October 21, 2010 with ClinicalTrials.gov identification number: NCT01226784 .

Comparison of the Levels of Pro-Inflammatory Cytokines Released in the Vastus Lateralis Muscle of Patients with Fibromyalgia and Healthy Controls during Contractions of the Quadriceps Muscle--A Microdialysis Study.

OBJECTIVE: Fibromyalgia is associated with central hyperexcitability, but it is suggested that peripheral input is important to maintain central hyperexcitability. The primary aim was to investigate the levels of pro-inflammatory cytokines released in the vastus lateralis muscle during repetitive dynamic contractions of the quadriceps muscle in patients with fibromyalgia and healthy controls. Secondarily, to investigate if the levels of pro-inflammatory cytokines were correlated with pain or fatigue during these repetitive dynamic contractions. MATERIAL AND METHODS: 32 women with fibromyalgia and 32 healthy women (controls) participated in a 4 hour microdialysis session, to sample IL-1ß, IL-6, IL-8, and TNF from the most painful point of the vastus lateralis muscle before, during and after 20 minutes of repeated dynamic contractions. Pain (visual analogue scale; 0-100) and fatigue Borg's Rating of Perceived Exertion Scale; 6-20) were assessed before and during the entire microdialysis session. RESULTS: The repetitive dynamic contractions increased pain in the patients with fibromyalgia (P < .001) and induced fatigue in both groups (P < .001). Perceived fatigue was significantly higher among patients with fibromyalgia than controls (P < .001). The levels of IL-1ß did not change during contractions in either group. The levels of TNF did not change during contractions in patients with fibromyalgia, but increased in controls (P < .001) and were significantly higher compared to patients with fibromyalgia (P = .033). The levels of IL-6 and IL-8 increased in both groups alike during and after contractions (P's < .001). There were no correlations between pain or fatigue and cytokine levels after contractions. CONCLUSION: There were no differences between patients with fibromyalgia and controls in release of pro-inflammatory cytokines, and no correlations between levels of pro-inflammatory cytokines and pain or fatigue. Thus, this study indicates that IL-1ß, IL-6, IL-8, and TNF do not seem to play an important role in maintenance of muscle pain in fibromyalgia.

Computerized training improves verbal working memory in patients with myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study.

OBJECTIVE: Patients with myalgic encephalomyelitis/chronic fatigue syndrome experience cognitive difficulties. The aim of this study was to evaluate the effect of computerized training on working memory in this syndrome. DESIGN: Non-randomized (quasi-experimental) study with no-treatment control group and non-equivalent dependent variable design in a myalgic encephalomyelitis/chronic fatigue syndrome-cohort. SUBJECTS: Patients with myalgic encephalomyelitis/chronic fatigue syndrome who participated in a 6-month outpatient rehabilitation programme were included in the study. Eleven patients who showed signs of working memory deficit were recruited for additional memory training and 12 patients with no working memory deficit served as controls. METHODS: Cognitive training with computerized working memory tasks of increasing difficulty was performed 30-45 min/day, 5 days/week over a 5-week period. Short-term and working memory tests (Digit Span - forward, backward, total) were used as primary outcome measures. Nine of the 11 patients were able to complete the training. RESULTS: Cognitive training increased working memory (p = 0.003) and general attention (p = 0.004) to the mean level. Short-term memory was also improved, but the difference was not statistically significant (p = 0.052) vs prior training. The control group did not show any significant improvement in primary outcome measures. CONCLUSION: Cognitive training may be a new treatment for patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Resistance exercise improves muscle strength, health status and pain intensity in fibromyalgia--a randomized controlled trial.

INTRODUCTION: Fibromyalgia (FM) is characterized by persistent widespread pain, increased pain sensitivity and tenderness. Muscle strength in women with FM is reduced compared to healthy women. The aim of this study was to examine the effects of a progressive resistance exercise program on muscle strength, health status, and current pain intensity in women with FM. METHODS: A total of 130 women with FM (age 22-64 years, symptom duration 0-35 years) were included in this assessor-blinded randomized controlled multi-center trial examining the effects of progressive resistance group exercise compared with an active control group. A person-centred model of exercise was used to support the participants' self-confidence for management of exercise because of known risks of activity-induced pain in FM. The intervention was performed twice a week for 15 weeks and was supervised by experienced physiotherapists. Primary outcome measure was isometric knee-extension force (Steve Strong®), secondary outcome measures were health status (FIQ total score), current pain intensity (VAS), 6MWT, isometric elbow-flexion force, hand-grip force, health related quality of life, pain disability, pain acceptance, fear avoidance beliefs, and patient global impression of change (PGIC). Outcomes were assessed at baseline and immediately after the intervention. Long-term follow up comprised the self-reported questionnaires only and was conducted after 13-18 months. Between-group and within-group differences were calculated using non-parametric statistics. RESULTS: Significant improvements were found for isometric knee-extension force (p = 0.010), health status (p = 0.038), current pain intensity (p = 0.033), 6MWT (p = 0.003), isometric elbow flexion force (p = 0.02), pain disability (p = 0.005), and pain acceptance (p = 0.043) in the resistance exercise group (n = 56) when compared to the control group (n = 49). PGIC differed significantly (p = 0.001) in favor of the resistance exercise group at post-treatment examinations. No significant differences between the resistance exercise group and the active control group were found regarding change in self-reported questionnaires from baseline to 13-18 months. CONCLUSIONS: Person-centered progressive resistance exercise was found to be a feasible mode of exercise for women with FM, improving muscle strength, health status, and current pain intensity when assessed immediately after the intervention. TRIAL REGISTRATION: ClinicalTrials.gov identification number: NCT01226784, Oct 21, 2010.