The association between violence against women and chronic pain: a systematic review and meta-analysis.

Violence against women is a phenomenon that involves at least 35% of women worldwide. Violence can be sexual, physical, and/or psychological, perpetrated by the partner, another family member, or a stranger. Violence is a public health problem because its consequences include higher morbidity, higher mortality, and short and long-term physical and psychological health diseases. Most studies prove an association between any type of violence and some chronic pain diagnoses but no one has done a complete collection of this evidence. This systematic review and meta-analysis aimed to evaluate whether this association is statistically significant, including the largest number of studies. Through the inclusion of 37 articles, the association has been demonstrated. Compared with no history of violence, women who did experience violence showed 2 times greater odds of developing chronic pain. The impact of violence was significant also on fibromyalgia separately, but not on pelvic pain.PROSPERO registrationPROSPERO CRD42023425477.

The (in)visibility of fibromyalgia through its symptoms and the challenges of its diagnosis and therapy.

OBJECTIVE: To analyze the social representations of fibromyalgia based on its symptoms and their influences on diagnosis and therapy. METHODS: Qualitative research with the application of the Theory of Social Representations and snowball sampling method. Semi-structured interviews were conducted with 30 adults diagnosed with fibromyalgia in the city of Rio de Janeiro, Brazil, between April 2020 and January 2021. Statistical and lexicographical analysis was performed using Alceste software. RESULTS: Pain, as a subjective phenomenon, complicates its legitimacy, diagnosis, and therapy, enhancing suffering. Insufficient information generates judgments, stereotypes, and prejudices. FINAL CONSIDERATIONS: Stigmas, prejudices, the variety and invisibility of symptoms make it difficult to objectify the disease within the Cartesian-biomedical frameworks, generating diagnostic pilgrimage, mistakes, and challenges in treatment. Such representations hinder relationships and the management of the disease. Deconstructing them is a way to better care for those with fibromyalgia. Raising awareness and spreading qualified information are important allies.

PRECISE trial (Pain RElief Combination Intervention StratEgies): protocol for the clinical trial of a pregabalin-melatonin combination for fibromyalgia.

INTRODUCTION: Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia. METHODS AND ANALYSIS: This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT-PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT-PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0-10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels). ETHICS AND DISSEMINATION: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen's University Health Sciences Research Ethics Board (Queen's HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings. TRIAL REGISTRATION NUMBER: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.

Evaluation of fibromyalgia frequency and quality of life in Notalgia paresthetica patients.

Based on the presence of chronic pain and the potential use of common treatment agents in Notalgia Paresthetica (NP) and Fibromyalgia Syndrome (FMS) for improvement, we aimed to investigate the frequency of FMS symptoms in NP patients and its impact on quality of life. This study is a case control cohort study including 26 patients diagnosed with NP and a total of 26 controls matched for age and gender. The 2016 revised fibromyalgia diagnostic criteria by the American College of Rheumatology (ACR) were used to inquire about FMS diagnosis criteria in the study. According to the 2016 ACR revised FMS diagnostic criteria, the frequency of FMS was significantly higher in the patient group (n = 9, 34.6%) compared to the control group (n = 2, 7.7%) (p = 0.042). The Wide Pain Index (WPI) score in the control group was 2.00 (3.25), while in the patient group, it was 4.00 (8.00), with a statistically significant difference between them (p < 0.035). Furthermore, significant statistical differences were found between the two groups in terms of Symptom Severity Scale (SSS), Fibromyalgia Score (FS), and FIQ (p < 0.035, p < 0.001, p < 0.001, respectively). In NP patients with accompanying FMS, Dermatology Life Quality Index was significantly more affected compared to those without FMS (p = 0.025). In conclusion, we recommend that NP patients be questioned about FMS, which is characterized by generalized pain, as well as regional neuropathic symptoms. Treatment success can be enhanced by using common agents in the treatment choice for accompanying FMS.

Investigating the Effectiveness of a Carb-Free Oloproteic Diet in Fibromyalgia Treatment.

Fibromyalgia (FM), a chronic disease with a high incidence in women, poses a significant challenge for diagnosis and treatment, especially due to the absence of specific biomarkers and the multifaceted nature of its symptoms, which range from neuromuscular pain to mood disorders and intestinal dysbiosis. While diagnosis currently relies on rheumatological clinical evaluations and treatment options mainly focus on symptom management, FM seems to have possible links with systemic metabolic dysfunctions with a common inflammatory root. In this context, a new therapeutic avenue emerges: could a therapeutic nutritional approach be the missing piece of the puzzle? Indeed, diet therapies employed particularly for metabolic syndromes proved recently to be efficacious for correcting systemic dysmetabolism and a high number of chronic inflammation conditions. In particular, the very-low-calorie ketogenic diet (VLCKD) demonstrated therapeutic benefits in many disorders. In the present study, we aimed to investigate the specific effects of two dietary interventions, namely the oloproteic VLCKD and the low-glycemic insulinemic (LOGI) diet, on two groups of female FM patients (FM1 and FM2) over a 45-day period. Utilizing clinical and laboratory tests, as well as non-invasive NMR metabolomic analysis of serum, urine, and saliva samples, we sought to uncover how these dietary regimens impact the metabolic dysfunctions associated with FM.

Assessment of Temporal Somatosensory Discrimination in Females with Fibromyalgia: Reliability and Discriminative Ability of a New Assessment Tool.

We assessed the test-retest reliability and discriminative ability of a somatosensory temporal discrimination (SSTD) assessment tool for fibromyalgia syndrome (FMS) and determined if pain-related variables were associated with SSTD performance. Twenty-five women with FMS and twenty-five asymptomatic women were assessed during two sessions 7 to 10 days apart. The proportion of correct responses (range 0-100) was calculated. Sociodemographic information was collected for both groups. The participants with FMS also completed the widespread pain index and the Brief Pain Inventory. Test-retest reliability was verified by calculating intraclass correlation coefficients. Discriminative ability was verified by a between-group comparison of scores using a t-test. Associations between SSTD score and pain variables were tested using Pearson or Spearman correlation coefficients. The test-retest reliability of the SSTD score was excellent (ICC > 0.9, CI: 0.79-0.96) for the asymptomatic group and good for the FMS group (ICC: 0.81, 95% CI: 0.62-0.91). The median (Q1-Q3) test session SSTD score differed significantly between the FMS 84.1 (71-88) and the asymptomatic 91.6 (83.4-96.1) groups (p < 0.001). Only pain duration was associated with the SSTD score. In conclusion, the new SSTD test seems reliable for people with FMS and is discriminative. Further studies should examine its sensitivity to change and correlations with other SSTD tests.

Astaxanthin alleviates fibromyalgia pain and depression via NLRP3 inflammasome inhibition.

Fibromyalgia is characterised by widespread chronic pain and is often accompanied by comorbidities such as sleep disorders, anxiety, and depression. Because it is often accompanied by many adverse symptoms and lack of effective treatment, it is important to search for the pathogenesis and treatment of fibromyalgia. Astaxanthin, a carotenoid pigment known for its anti-inflammatory and antioxidant properties, has demonstrated effective analgesic effects in neuropathic pain. However, its impact on fibromyalgia remains unclear. Therefore, in this study, we constructed a mouse model of fibromyalgia and investigated the effect of astaxanthin on chronic pain and associated symptoms through multiple intragastrical injections. We conducted behavioural assessments to detect pain and depression-like states in mice, recorded electroencephalograms to monitor sleep stages, examined c-Fos activation in the anterior cingulate cortex, measured activation of spinal glial cells, and assessed levels of inflammatory factors in the brain and spinal cord, including interleukin (IL)-1ß, IL-6, and tumour necrosis factor- α(TNF-α).Additionally, we analysed the expression levels of IL-6, IL-10, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Apoptosis-associated speck-like protein containing CARD, and Caspase-1 proteins. The findings revealed that astaxanthin significantly ameliorated mechanical and thermal pain in mice with fibromyalgia and mitigated sleep disorders and depressive-like symptoms induced by pain. A potential mechanism underlying these effects is the anti-inflammatory action of astaxanthin, likely mediated through the inhibition of the NLRP3 inflammasome, which could be one of the pathways through which astaxanthin alleviates fibromyalgia. In conclusion, our study suggests that astaxanthin holds promise as a potential analgesic medication for managing fibromyalgia and its associated symptoms.

Inflammation, Autoimmunity, and Infection in Fibromyalgia: A Narrative Review.

Fibromyalgia (FM) is a chronic disease characterized by widespread musculoskeletal pain of unknown etiology. The condition is commonly associated with other symptoms, including fatigue, sleep disturbances, cognitive impairment, and depression. For this reason, FM is also referred to as FM syndrome. The nature of the pain is defined as nociplastic according to the latest international classification and is characterized by altered nervous sensitization both centrally and peripherally. Psychosocial conditions have traditionally been considered critical in the genesis of FM. However, recent studies in animal models and humans have provided new evidence in favor of an inflammatory and/or autoimmune pathogenesis. In support of this hypothesis are epidemiological data of an increased female prevalence, similar to that of autoimmune diseases, and the frequent association with immune-mediated inflammatory disorders. In addition, the observation of an increased incidence of this condition during long COVID revived the hypothesis of an infectious pathogenesis. This narrative review will, therefore, discuss the evidence supporting the immune-mediated pathogenesis of FM in light of the most current data available in the literature.

[Post-Covid Syndrome, Sick Building Syndrome, Silicone Breast Syndrome, Choric Fatigue Syndrome, Fibromyalgia -Autoimmunity to the Autonomic Nervous System].

INTRODUCTION: Post-Covid Syndrome, Sick Building Syndrome, Silicone Breast Syndrome, Choric Fatigue Syndrome, Fibromyalgia -Autoimmunity to the Autonomic Nervous System.

[THE MUSCULAR COMPONENT OF FIBROMYALGIA PATHOPHYSIOLOGY].

INTRODUCTION: Fibromyalgia syndrome (FMS) is a chronic pain syndrome, prevalent in women more than men. The main symptoms are widespread musculoskeletal pain, fatigue, and weakness. To date, the pathophysiological mechanisms are unclear, and there are several pathogenic theories elucidating this condition. In this review, we summarized articles published in the past few years, regarding the effect of musculoskeletal dysfunction on FMS. We focused on the musculoskeletal system and central nervous system (CNS) disarrays.

Patient preferences for models of care for fibromyalgia: A discrete choice experiment.

BACKGROUND: Fibromyalgia is a common reason for referral to a rheumatologist and is a centralised pain state with symptoms beginning in adolescence/early adulthood and manifests as pain throughout the body, fatigue and cognitive dysfunction. Whilst there is considerable evidence on effective treatments, diagnosis and management are complex. There is almost no evidence on how to organise health services to deliver recommended therapies. The aim of the current study was to understand patient preferences for different features of healthcare services for fibromyalgia. METHODOLOGY: We use the Discrete Choice Experiment Method (DCE), a choice-based survey that quantifies preferences for attributes of goods, services or policy interventions, to elicit preferences in relation to alternative models of care for people with fibromyalgia. In this study, attributes describe different models of care for fibromyalgia. We based attributes and levels on earlier phases of the PACFiND project and a literature review on fibromyalgia models of care. The final analysis sample consisted of 518 respondents who completed the survey in full. RESULTS: The final analysis sample consisted of 518 respondents ((patients living in the UK, over 18 years old, with a diagnosis of fibromyalgia), who completed the survey in full. The model of care most preferred is one characterised by earlier diagnosis and ongoing management by a Rheumatologist, via Face-to-face or Phone/video call appointments, with a stronger preference for the latter mode of support. The most preferred treatment was Medication, followed by Physical Therapy, with the least preferred being Talking Therapy. Relative to a Waiting Time for treatment of 6 months, respondents would prefer a lower Waiting Time of 3 months and dislike waiting 12 months for treatment. Respondents showed willingness to receive Ongoing Help and Advice by a Nurse Practitioner or a GP, instead of a Specialist Rheumatologist, provided they were compensated by other changes in the model of care. CONCLUSION: This study has found that, although respondents express a preference for specialist care, provided by a Rheumatologist, they may be willing to trade-off this preference against other features within a model of care. This willingness to accept a different skill-mix (e.g., appointments with a GP or a Nurse Practitioner) has important implications for practice and policy, as this is a more feasible option in settings where the availability of specialist care is highly constrained.

Hypocapnia in women with fibromyalgia.

OBJECTIVES: The purpose of this study was to investigate whether people with fibromyalgia (FM) have dysfunctional breathing by examining acid-base balance and comparing it with healthy controls. METHODS: Thirty-six women diagnosed with FM and 36 healthy controls matched for age and gender participated in this cross-sectional study. To evaluate acid-base balance, arterial blood was sampled from the radial artery. Carbon dioxide, oxygen, bicarbonate, base excess, pH and lactate were analysed for between-group differences. Blood gas analyses were performed stepwise on each individual to detect acid-base disturbance, which was categorized as primary respiratory and possible compensation indicating chronicity. A three-step approach was employed to evaluate pH, carbon dioxide and bicarbonate in this order. RESULTS: Women with FM had significantly lower carbon dioxide pressure (p = 0.013) and higher lactate (p = 0.038) compared to healthy controls at the group level. There were no significant differences in oxygen pressure, bicarbonate, pH and base excess. Employing a three-step acid-base analysis, 11 individuals in the FM group had a possible renally compensated mild chronic hyperventilation, compared to only 4 among the healthy controls (p = 0.042). CONCLUSIONS: In this study, we could identify a subgroup of individuals with FM who may be characterized as mild chronic hyperventilators. The results might point to a plausible dysfunctional breathing in some women with FM.

Well-Being Therapy for Fibromyalgia: A Case Report.

ABSTRACT: Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain, fatigue, anxiety, depression, and sleep disturbances, significantly impairing quality of life and psychological well-being. Well-being therapy (WBT) is a brief psychotherapeutic intervention aimed at increasing well-being and optimizing functioning, which has proven effective in treating various conditions involving pain and psychological or psychiatric symptoms. We describe a case study of a 22-year-old university student experiencing FMS, highlighting the far-reaching effects of the condition on her quality of life. After eight sessions of WBT, there was a marked improvement in subjective well-being and euthymia, as well as a decrease in pain perception, improved ability to manage stress, reduced allostatic overload despite the presence of stressors, improved social relationships, and increased self-efficacy. The positive effects of WBT continued at 3-month follow-up, suggesting that WBT may represent a short-term effective intervention for patients with FMS.

Role of ERK in gender difference of fibromyalgia pain.

This study investigated the ERK pathway of the peripheral nervous system and discovered a gender-specific pattern of ERK activation in the dorsal root ganglion of an acid-induced chronic widespread muscular pain model. We employed a twice acid-induced chronic musculoskeletal pain model in rats to evaluate mechanical pain behavior in both male and female groups. We further conducted protein analysis of dissected dorsal root ganglions from both genders. Both male and female rats exhibited a similar pain behavior trend, with females demonstrating a lower pain threshold. Protein analysis of the dorsal root ganglion (DRG) showed a significant increase in phosphorylated ERK after the second acid injection in all groups. However, phosphorylation of ERK was observed in the dorsal root ganglion, with higher levels in the male ipsilateral group compared to the female group. Moreover, there was a no difference between the left and right sides in males, whereas the significant difference was observed in females. In conclusions, the administration of acid injections induced painful behavior in rats, and concurrent with this, a significant upregulation of pERK was observed in the dorsal root ganglia, with a greater magnitude of increase in males than females, and in the contralateral side compared to the ipsilateral side. Our findings shed light on the peripheral mechanisms underlying chronic pain disorders and offer potential avenues for therapeutic intervention.

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.

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.

Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries.

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Reduced sympathetic activity is associated with the development of pain and muscle atrophy in a female rat model of fibromyalgia.

Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain accompanied by fatigue and muscle atrophy. Although its etiology is not known, studies have shown that FM patients exhibit altered function of the sympathetic nervous system (SNS), which regulates nociception and muscle plasticity. Nevertheless, the precise SNS-mediated mechanisms governing hyperalgesia and skeletal muscle atrophy in FM remain unclear. Thus, we employed two distinct FM-like pain models, involving intramuscular injections of acidic saline (pH 4.0) or carrageenan in prepubertal female rats, and evaluated the catecholamine content, adrenergic signaling and overall muscle proteolysis. Subsequently, we assessed the contribution of the SNS to the development of hyperalgesia and muscle atrophy in acidic saline-injected rats treated with clenbuterol (a selective ß2-adrenergic receptor agonist) and in animals maintained under baseline conditions and subjected to epinephrine depletion through adrenodemedullation (ADM). Seven days after inducing an FM-like model with acidic saline or carrageenan, we observed widespread mechanical hyperalgesia along with loss of strength and/or muscle mass. These changes were associated with reduced catecholamine content, suggesting a common underlying mechanism. Notably, treatment with a ß2-agonist alleviated hyperalgesia and prevented muscle atrophy in acidic saline-induced FM-like pain, while epinephrine depletion induced mechanical hyperalgesia and increased muscle proteolysis in animals under baseline conditions. Together, the results suggest that reduced sympathetic activity is involved in the development of pain and muscle atrophy in the murine model of FM analyzed.