One year in review 2020: fibromyalgia.

Fibromyalgia (FM) is a frequently encountered syndrome that is characterised by chronic widespread pain, fatigue, sleep disturbances, and many other symptoms that impair the quality of life. Its aetiopathogenesis is still unclear but, although there is no specific therapy, a number of pharmacological and non-pharmacological therapies are available. The aim of this review is to describe the most recent findings concerning the diagnosis, aetiopathogenesis and treatment of FM published between January 2019 and January 2020. They include the new concept of nociplastic pain, some neuroendocrine and metabolic alterations found in FM patients, and investigations concerning not only novel applications of old drugs, but also, and in particular, complementary therapies, such as the hyperbaric oxygen chamber, ozone therapy and mindfulness-based interventions.

One year in review 2019: fibromyalgia.

Fibromyalgia is characterised by chronic pain, fatigue and functional symptoms. Its aetiopathogenesis is still a matter of debate, but various pharmacological and non-pharmacological therapies are currently available for its treatment. We review the literature concerning the most recent findings related to the aetiopathogenesis, diagnosis, clinical aspects and treatment of FM published between January 2018 and January 2019.

Role for a water-soluble form of CoQ10 in female subjects affected by fibromyalgia. A preliminary study.

Decreased antioxidant capacity and increased oxidative stress have been observed in fibromyalgia patients. Some trials have also shown that CoQ10 levels are reduced in these patients but that supplementation can restore levels and reduce fibromyalgia symptoms, including pain and fatigue. We evaluated the effect of administration of a finished form of CoQ10 (DDM Chinone®) at a dose of 200 mg×2/day in 22 female subjects with a diagnosis of fibromyalgia in a randomized, open-label, cross-over study. Our results show that, compared to a control group, administration of CoQ10 significantly improved most pain-related outcomes by 24-37%, including fatigue (by ~22%) and sleep disturbance (by ~33%). These results confirm the considerable role played by CoQ10 in reducing pain, fatigue, and sleep disturbance in subjects affected by fibromyalgia.

Salivary psoriasin (S100A7) correlates with diffusion capacity of carbon monoxide in a large cohort of systemic sclerosis patients.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive fibrosis of the skin and the internal organs. In a previous work we suggested a correlation between levels of salivary psoriasin (S100A7) and pulmonary involvement in SSc patients. The goals of this study are to determine the distribution characteristics of psoriasin in whole saliva (WS) of SSc and healthy donor populations and define its predictive value on diffusion capacity of carbon monoxide (DLCO), along with others clinical parameters. METHODS: Salivary level of psoriasin was determined by ELISA kit in 134 SSc patients, 63 Raynaud syndrome patients, 40 patients affected by other connective diseases (non-case) and 74 healthy control subjects. RESULTS: A significant increase of salivary psoriasin was observed in SSc patients when compared with other healthy and pathological controls. Moreover, we confirmed the efficacy of salivary psoriasin to correlate with DLCO in a large cohort of SSc patients. CONCLUSIONS: Overall our results suggest a rapid, non invasive and low costing method which can help clinicians in the evaluation of SSc pulmonary involvement.

Transdiagnostic factors across fibromyalgia and mental disorders: sleep disturbances may play a key role. A clinical review.

Sleep disturbances, affective disorders, pain and fatigue are often present in individuals affected by fibromyalgia (FM). The pathophysiology of FM is not yet well understood and, to date, no treatment has been proven to be fully effective in alleviating all symptoms. Adopting a transdiagnostic perspective could thus be useful for clinicians: treatment would target a transdiagnostic process across a range of disturbances, not just a single disorder. The aim of this review is to revise the available literature about the potential role of sleep disturbances as a transdiagnostic process in FM symptomatology and mood or anxiety disorders comorbidity. We are proposing a model under which sleep disturbances can play a central role. Because conditions of sleep loss are related to the activation of the stress system, including the activation of the inflammation system, we propose this mechanism as a key one: it can be shared by mental, sleep disturbances and pain in FM and it may explain, in part, the high levels of comorbidity between them. In this frame-work sleep disturbances may play a key role and be the target of therapeutic strategies across FM symptomatology and mental disorders.

One year in review 2016: fibromyalgia.

Fibromyalgia (FM) syndrome is a chronic disease with unknown aetiology, characterised by widespread pain, fatigue and other functional symptoms. We reviewed the literature of the past year to underline the recent progress in the etiopathogenesis, assessment and therapies of this syndrome, evaluating the articles published between January 2015 and January 2016.

Fibromyalgia and nutrition: what news?

Fibromyalgia syndrome (FM) is a chronic, generalised pain condition usually accompanied by several associated symptoms, such as fatigue, sleep disturbance, headache, irritable bowel syndrome and mood disorders. Different medical treatments are used to treat fibromyalgia and the recent guidelines suggest that the optimal treatment consists in a multidisciplinary approach with a combination of pharmacological and non-pharmacological treatment modalities. Among non-pharmacological treatment, nutrition is a promising tool for FM patients. The aim of this review is to update the present knowledge about fibromyalgia and nutrition by means of a systematic search performed on Medline from January 2000 to December 2014. Nutritional deficiencies have been described in FM patients and the benefits of specific diet and nutritional supplementation are shown. Obesity and overweight, often present in FM patients, are related to the severity of FM worsening the quality of life in terms of higher pain, fatigue, worsened sleep quality and higher incidence of mood disorders. Weight control is thus an effective tool to improve the symptoms. Moreover, it seems reasonable to eliminate some foods from the diet of FM patients, for example excitotoxins. Non-coeliac gluten sensitivity is increasingly recognised as a frequent condition with similar manifestations which overlap with those of FM. The elimination of gluten from the diet of FM patients is recently becoming a potential dietary intervention for clinical improvement. In summary, this review reveals the potential benefit of specific dietary interventions as non-pharmacological tools as part of a multidisciplinary treatment for FM patients.

Algo-dysfunctional syndromes: a critical digest of the recent literature.

The etiopathogenesis of the algo-dysfunctional syndromes, which include chronic fatigue syndrome, fibromyalgia and irritable bowel syndrome, is still debated, but it is widely accepted that it is best described by a multifactorial model that include genes, environmental factors such as external infections, inflammation, dietary habits, impaired endogenous cortisol production, the aberrant activation of some areas of the central nervous system, and small peripheral nervous fibre damage. This complexity suggests that they should be managed by means of a multidisciplinary approach involving the use of both pharmacological and non-pharmacological treatments. The aim of this review is to discuss the most recent scientific acquisitions concerning these syndromes and their treatment.

A multidisciplinary approach to study a couple of monozygotic twins discordant for the chronic fatigue syndrome: a focus on potential salivary biomarkers.

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a severe, systemic illness characterized by persistent, debilitating and medically unexplained fatigue. The etiology and pathophysiology of CFS remains obscure, and diagnosis is formulated through the patient's history and exclusion of other medical causes. Thereby, the availability of biomarkers for CFS could be useful for clinical research. In the present study, we used a proteomic approach to evaluate the global changes in the salivary profile in a couple of monozygotic twins who were discordant for CFS. The aim was to evaluate differences of salivary protein expression in the CFS patient in respect to his healthy twin. METHODS: Saliva samples were submitted to two-dimensional electrophoresis (2DE). The gels were stained with Sypro, and a comparison between CFS subject and the healthy one was performed by the software Progenesis Same Spot including the Analysis of variance (ANOVA test). The proteins spot found with a ≥2-fold spot quantity change and p<0.05 were identified by Nano-liquid chromatography electrospray ionization tandem mass spectrometry. To validate the expression changes found with 2DE of 5 proteins (14-3-3 protein zeta/delta, cyclophilin A, Cystatin-C, Protein S100-A7, and zinc-alpha-2-glycoprotein), we used the western blot analysis. Moreover, proteins differentially expressed were functionally analyzed using the Ingenuity Pathways Analysis software with the aim to determine the predominant canonical pathways and the interaction network involved. RESULTS: The analysis of the protein profiles allowed us to find 13 proteins with a different expression in CFS in respect to control. Nine spots were up-regulated in CFS and 4 down-regulated. These proteins belong to different functional classes, such as inflammatory response, immune system and metabolism. In particular, as shown by the pathway analysis, the network built with our proteins highlights the involvement of inflammatory response in CFS pathogenesis. CONCLUSIONS: This study shows the presence of differentially expressed proteins in the saliva of the couple of monozygotic twins discordant for CFS, probably related to the disease. Consequently, we believe the proteomic approach could be useful both to define a panel of potential diagnostic biomarkers and to shed new light on the comprehension of the pathogenetic pathways of CFS.

Fibromyalgia: a critical digest of the recent literature.

Fibromyalgia (FM) syndrome is a chronic disease with unknown etiology, characterised by widespread pain and fatigue. Moreover, several patients manifest non-specific symptoms such as sleep disturbances, mood disorders, and neurocognitive impairment. We have reviewed the literature of the past year to underline the progress of research in the fields of etiopathogenesis, therapies and assessment, considering articles published between November 2012 and November 2013.

The influence of psychiatric comorbidity on sexual satisfaction in fibromyalgia patients.

OBJECTIVES: To investigate the influence of psychiatric comorbidity on sexual satisfaction in premenopausal and postmenopausal female affected by fibro-myalgia (FM). METHODS: We enrolled 100 FM females and 40 age-matched healthy females. Psychiatric diagnoses were carried out using the Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition; sexual satisfaction was evaluated using the Index of Sexual Satisfaction (ISS), clinical assessment included the Fibromyalgia Impact Questionnaire (FIQ), tender point (TP) count and pain evaluation by means of a visual analogue scale (VAS). RESULTS: The data were analysed according to the presence and absence of psychiatric comorbidity in FM patients (all FM, only FM, FM with a lifetime psychiatric disorder, FM with a current psychiatric disorder). FM patients with a current psychiatric comorbidity (n=24) showed ISS values significantly higher (41.5±17.5) with respect to patients with only FM (n=45) (27.3±17.4, p<0.05) and healthy controls (24.1±12.8, p<0.01). The FIQ values of patients with current psychiatric comorbidity were significantly higher (68.4±13.5) compared to the values of patients with only FM (55.7±17.9) (p<0.05). No differences were found between VAS pain or the number of TP of the three groups of patients. CONCLUSIONS: Our results suggest that psychiatric comorbidity has more influence on the sexual satisfaction of FM patients than the presence of the rheumatic disease itself. Because the ISS gives an indication of the relationship with partners, this finding suggests that emotional aspects may play a crucial role in sexual behavior, in particular in those FM patients with current psychiatric comorbidity.

A multidisciplinary approach to study the effects of balneotherapy and mud-bath therapy treatments on fibromyalgia.

OBJECTIVES: To study the effects of both balneotherapy and mud-bath therapy treatments in patients affected by primary fibromyalgia (FM) using rheumatological, psychiatric, biochemical and proteomic approaches. METHODS: Forty-one FM patients (39 females, 2 males), who fulfilled the American College of Rheumatology criteria received a 2-week thermal therapy programme consisting of therapy once daily for 6 days/week. Twenty-one patients received mud-bath treatment, while the other twenty balneotherapy. Pain, symptoms, and quality of life were assessed. Oxytocin, brain-derived neurotrophic factor (BDNF), ATP and serotonin transporter levels during therapy were assayed. Comparative whole saliva (WS) proteomic analysis was performed using a combination of two-dimensional electrophoresis (2DE) and mass spectrometry techniques. RESULTS: We observed a reduction in pain, FIQ values and improvement of SF36 in both groups of patients treated with mud-bath or balneotherapy. The improvement of the outcome measures occurred with different timing and duration in the two spa treatments. A significant decrease in BDNF concentrations was observed either after balneotherapy or mud-bath therapy when assayed after twelve weeks, while no significant change in oxytocin levels, ATP levels and serotonin transporter were detected. Significant differences were observed for phosphoglycerate mutase1 (PGAM1) and zinc alpha-2-glycoprotein 1 (AZGP1) protein expression. CONCLUSIONS: Our results showed that the thermal treatment might have a beneficial effect on the specific symptoms of the disease. In particular, while balneotherapy gives results that in most patients occur after the end of the treatment but which are no longer noticeable after 3 months, the mud-bath treatment gives longer lasting results.

Methodological approach to depressive symptoms in fibromyalgia patients.

OBJECTIVES: Depression is a common comorbid condition in fibromyalgia (FM) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with FM due to overlapping symptoms between the two conditions. This review aims to present the most used rating scales for depression in FM patients by discussing their potential drawbacks. Moreover, we aimed to discuss the possible approach to mood symptoms in FM patients according to the mood spectrum model. METHODS: We included the main scales that have been used previously to assess depression in FM according to the literature data. Then, we reviewed the studies exploring the prevalence and the impact of sub-threshold mood symptoms on FM patients. RESULTS: Rating scales for depression such as the Hamilton Rating Scale for Depression, the Hospital Anxiety and Depression Scale, the Center for Epidemiologic Studies Depression Scale, the Beck Depression Inventory, the Montgomery Asberg Depression Rating Scale and the Zung Self-Rating Depression Scale have been largely used. However, almost all these instruments could suffer from a criterion contamination bias by somatic symptoms of chronic pain patients. Many studies have shown a critical role of sub-threshold mood psychopathology on worsening quality of life, disability and pain in FM patients. Specific questionnaires (Mood Spectrum Self-Report [MOODS-SR]) for subsyndromal phenomenology have been validated and used also in patients with medical diseases. CONCLUSIONS: The need of a careful screening of depressive symptoms and of their proper management is primary in FM. In our opinion instruments like MOODS-SR are particularly suitable for screening FM patients because they allow to recognise also sub-threshold mood symptoms with minimal contamination by somatic conditions.

Dysfunctional syndromes and fibromyalgia: a 2012 critical digest.

Medically 'unexplained' chronic disorders remain a challenge for clinicians because the patients with these syndromes have a wide range of symptoms, including pain, impaired concentration, sleep disturbances, fatigue and mood disorders, as well as functional problems and difficulties in carrying out the activities of daily living. Such disorders are the result of a complex physiological interaction of central and peripheral nervous signaling that leads to a highly individual symptom complex, although some of them seem to be related to one another, especially in terms of the mechanism of chronicity and pain amplification, and the co-occurrence of fatigue, sleep alterations, mood disturbances and cognitive impairment. This review will discuss the recent literature concerning the most common dysfunctional disorders: fibromyalgia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, and irritable bowel syndrome.

The impact of mood, anxiety, and sleep disorders on fibromyalgia.

INTRODUCTION: Several studies carried out mainly in North America revealed high rates of mood, anxiety and sleep disorders in patients with fibromyalgia (FM), while the information in other countries is scant. Therefore, we aimed at investigating the prevalence and the impact of such conditions on the health-related quality of life (HRQoL) and the severity of pain in a sample of Italian FM patients. METHODS: One-hundred and sixty-seven women suffering from primary FM were consecutively enrolled. Psychiatric diagnoses were made by means of DSM-IV criteria. The HRQoL and the severity of pain were measured through the Medical Outcomes Study 36-item Short-Form Health Survey (MOS-SF-36) and the FM Impact Questionnaire (FIQ). RESULTS: Fibromyalgia patients showed a high rate (80.8%) of lifetime and/or current comorbidity with mood and anxiety disorders. Patients with psychiatric comorbidity resulted significantly more impaired on the Mental Component Summary score of the MOS-SF-36 and showed a higher FIQ total score than those suffering from FM only. The severity of pain was associated with current psychiatric comorbidity. Patients with current mood disorders showed significantly lower Mental and Physical Component Summary scores of the MOS-SF-36 and higher FIQ total scores than those with current anxiety disorders or those without psychiatric comorbidity. Finally, patients with sleep disorders reported a lower HRQoL than those with a normal sleep, and specifically those with difficulty in falling in sleep had higher severity of pain. CONCLUSION: Psychiatric comorbidity, in particular with mood disorders, provokes a significant impairment of the HRQoL and, when current, a higher severity of pain in FM patients.

A proposal of simple calculation (ERI calculator) to predict the early response to TNF-α blockers therapy in rheumatoid arthritis.

Increasing evidence has been accumulated for treating rheumatoid arthritis (RA) with TNF-α blocking agents. The formulation and definition of an early indicator of patient's reactivity during therapy may be extremely simplified by a mathematical model of clinical response. We analyzed the most significant clinical and laboratory parameters of response of 35 homogeneous patients (30 women, 5 men mean age ± SD: 52.31 ± 12.30 years) treated with adalimumab 40 mg every 2 weeks associated with methotrexate (MTX) 10-15 mg/week and with a stable dosage of steroids for 30 weeks. The over time trend of the studied parameters showed a linear response, which has allowed the realization of a simple mathematical model. The formula derived from this mathematical model was then applied and therefore validated in a group of 121 patients previously treated with several anti-TNF-alpha agents for at least 6 months. We drafted a mathematical model (early response indicator, ERI) that, by using a simple calculation, allows us to identify a high percentage of responder patients after only 2 weeks of treatment. ERI identified a high percentage (88%) of patients responding after only 2 weeks, as was confirmed at weeks 30; the use of ERI calculation after 6 weeks increases the proportion of responding patients to 92% with a percentage of false negatives of only 12%. ERI could be a useful tool to early differentiate the responder from the non-responder patients.

Correspondence between salivary proteomic pattern and clinical course in primary Sjögren syndrome and non-Hodgkin's lymphoma: a case report.

BACKGROUND: In the last years human proteomic has represented a promising tool to promote the communication between basic and clinical science. METHODS: To explore the correspondence between salivary proteomic profile and clinical response, herein, we used a proteomic approach to analyse the whole saliva of a patient with primary Sjögren's Syndrome (pSS) and non-Hodgkin's-MALT type parotid lymphoma before, during and after a standard treatment with cyclophosphamide (CTX) and rituximab (RTX). To identify any discriminatory therapeutic salivary biomarker patient's whole saliva was collected at the baseline, after the fourth infusion of rituximab, and on remission and analysed combining two-dimensional electrophoresis (2DE) and MALDI-TOF/TOF mass spectrometry. RESULTS: Proteomic results obtained from the comparison of salivary samples indicated several qualitative and quantitative modifications in the salivary expression of putative albumin, immunoglobulin J chain, Ig kappa chain C region, alpha-1-antitrypsin, haptoglobin and Ig alpha-1 chain C region. CONCLUSION: This study suggests that clinical and functional changes of the salivary glands driven by autoimmune and lymphoproliferative processes might be reflected in patients' whole saliva proteins, shedding new light on the potential usefulness of salivary proteomic analysis in the identification of prognostic and therapeutic biomarkers for patients with pSS and non Hodgkin's lymphomas.

Osteopontin is associated with increased arterial stiffness in rheumatoid arthritis.

Rheumatoid arthritis (RA) patients are characterized by increased arterial stiffness, an independent predictor of cardiovascular risk. It has been suggested that osteopontin (OPN), a cytokine involved in RA pathogenesis, might have vascular effects. To study a possible relationship between OPN and arterial stiffness, aortic pulse wave velocity (PWV) was measured by tonometry in 69 patients (41 with RA, 28 with systemic sclerosis [SSc]) and 18 healthy controls. Plasma OPN levels, oxidative stress markers, and endothelin 1 (ET-1) were assessed. OPN levels were significantly (P < 0.05) higher in RA (median 9.93, range 4.36-47.80 ng/mL) than in SSc (4.3, 2.1-19.7 ng/mL) or controls (5.2, 4.1-9.4 ng/mL). In RA patients, log-OPN was related to log-C-reactive protein (log-CRP) (r = 0.30, P < 0.05), age (r = 0.38, P < 0.01), Health Assessment Questionnaire (HAQ) (r = 0.58, P < 0.0001), and inversely related to total cholesterol (r = -0.33, P < 0.05) and apolipoprotein A (apoA) (r = -0.58, P < 0.001), but not to oxidative stress markers and ET-1. PWV was similar in RA (median 8.1, range 4.7-16.4 m/s) and SSc (median 8.7, range 7.1-13.1 m/s), but significantly greater (P < 0.01) than controls (median 7.5, range 4.1-10.4 m/s). Aortic PWV was related to log-OPN (r = 0.40, P < 0.01) only in RA patients. It also was related to age (r = 0.34, P < 0.05), mean blood pressure (r = 0.44, P < 0.001), and HAQ (r = 0.48, P < 0.001). In multiple regression analysis (r(2) = 0.36), including confounders, log-OPN remained a significant predictor (P < 0.05) of PWV in RA. Elevated plasma OPN levels are associated with increased arterial stiffness in RA patients, suggesting that this protein might represent a bridge protein between inflammation and the consequent joint damage and cardiovascular risk in RA patients.

Muscle modifications in fibromyalgic patients revealed by surface electromyography (SEMG) analysis.

BACKGROUND: Several studies have been carried out in order to investigate surface electromyography (SEMG) response on fibromyalgic (FM) patients. Some studies failed to demonstrate differences between FM patients and healthy individuals while others found differences in SEMG parameters. Different muscular region have been analyzed in FM patients and heterogeneity is also produced because of the different ways in which the SEMG technique is used. The aims of this study were to evaluate muscle modifications by SEMG analysis in FM women with respect to a sample of healthy controls and to investigate the relationships between SEMG parameters and the clinical aspects of the disease. METHODS: SEMG was recorded in 100 FM women (48.10 +/- 11.96 yr) and in 50 healthy women (48.60 +/- 11.18 yr), from the tibialis anterior and the distal part of vastus medialis muscle during isometric contraction. Initial values and rate of change of median spectral frequency (MDF) and conduction velocity (CV) of the SEMG signal were calculated.The clinical parameters "Fibromyalgia Impact Questionnaire", pain, tender points, tiredness were evaluated and the relationships between these data and the SEMG results were also studied. For the statistical analysis Mann-Whitney test, chi-square test and Spearman correlation were used. RESULTS: MDF absolute values and the so-called Fatigue Index (FI) were significantly lower (p < 0.001) in both muscles studied in FM patients (MDF: 93.2 microV; FI: 1.10, 0.89) with respect to healthy controls (MDF: 138.2 microV; FI: 2.41, 1.66) and a smaller reduction in the percentage values of MDF was observed in FM patients vs controls (22% vs 38%). A significant correlation was found between the SEMG parameter decrement of normalized median frequency (MNF) (%) and seriousness of FM (evaluated by means of tender points). CONCLUSION: We have found some interesting muscle modifications in FM patients with respect to healthy controls, regarding MDF, CV and FI values which resulted significantly lower in FM. Patients might have a different fiber recruitment or a possible atrophy of type II fibers suggesting that they are not able to reach muscle relaxation.

Putative salivary biomarkers useful to differentiate patients with fibromyalgia.

Fibromyalgia (FM) is a chronic pain disorder characterized by widespread pain and associated with unspecific symptoms. So far, no laboratory tests have been validated. The aim of the present study was to investigate the presence in saliva of potential diagnostic and/or prognostic biomarkers which could be useful for the management of FM patients. Specifically, the salivary profile of FM patients was compared with those of healthy subjects, subjects suffering migraine (model of non-inflammatory chronic pain), and patients affected by rheumatoid arthritis (model of inflammatory chronic pain). For proteomics analysis 2-DE and SELDI-TOF-MS were applied. From 2-DE serotransferrin and alpha-enolase were found differentially expressed in FM. Hence, their expression was validated by ELISA together with phosphoglycerate-mutase-I and transaldolase, which were found in a previous work. Moreover, ROC curve was calculated by comparing FM patients versus control subjects (healthy plus migraine) to investigate the discriminative power of biomarkers. The best performance was obtained by combining alpha-enolase, phosphoglycerate-mutase-I and serotransferrin. On the other hand, none of the candidate proteins showed a statistical correlation with clinical features. Finally, preliminary SELDI analysis highlighted two peaks whose identification need to be validated. Overall, these results could be useful in supporting the clinical diagnosis of FM. SIGNIFICANCE: FM is one of the most common chronic pain condition which is associated with significant disability. The fibromyalgic pain is a peculiar characteristic of this disease and FM patients suffer from reduced quality of life, daily functioning and productivity. Considering the deep complexity of FM, the discovery of more objective markers is crucial for supporting clinical diagnosis. Therefore, the aim of the present study was the selection of biomarkers effectively associated with fibromyalgic pain which will enable clinicians to achieve an unambiguous diagnosis, and to improve approaches to patients' management. We defined a panel of 3 salivary proteins which could be one of the criteria to be taken into account. Consequently, the identification of disease salivary biomarkers could be helpful in detecting FM clusters and targeted treatment. Actually, our future perspective foresees to develop a simple, rapid and not invasive point-of-care testing which will be of use during the diagnostic process. In addition, the present results can offer a clue for shedding light upon the complex entity of such a disease like FM.