Comparison of the serum brain-derived neurotrophic factor (BDNF) between fibromyalgia and nociceptive pain groups; and effect of duloxetine on the BDNF level.

BACKGROUND: The primary objective was to compare the serum brain-derived neurotrophic factor (BDNF) level in the patients with two types of pain: fibromyalgia (FM) and non-FM nociceptive pain (non-FM NP). The secondary objective was to investigate the effect of duloxetine on serum BDNF in FM patients and assess the direction of BDNF changes' relation to clinical parameters' alterations. METHODS: This is a study on 73 patients (50 FM and 23 non-FM chronic non-inflammatory pain patients). Serum BDNF was first compared between both groups. Patients with FM, then prospectively, underwent standardized FM treatment with duloxetine maximized to 60 mg/day. The Revised Fibromyalgia Impact Questionnaire (FIQR), Short-Form Health Survey (SF-12), pain visualized analog scale (pain VAS), Beck Depression Inventory-II (BDI-II), polysymptomatic distress scale (PSD) and serum BDNF were measured and compared at baseline and 4 weeks after treatment in FM group. RESULTS: The mean of adjusted BDNF level in the FM group had no significant difference than the non-FM NP group ((5293.5 ± 2676.3 vs. 6136.3 ± 4037.6; P value = 0.77). Using linear mixed model, we showed that duloxetine reduced BDNF level significantly in FM patients, even after adjusting for depression, pain and severity of the disease (P < 0.01). The FIQR, BDI-II, PSD, and pain VAS improved significantly after duloxetine treatment. CONCLUSIONS: Non-significant BDNF level difference between FM and non-FM nociceptive pain suggested that peripheral BDNF is not a pathophysiological feature of FM. The decreased BDNF level parallel with improvement of PSD/pain scores after duloxetine treatment indicates BDNF alteration in the pain modulation process, regardless of cause and effect.

Effect of vitamin B6 on pain, disease severity, and psychological profile of fibromyalgia patients; a randomized, double-blinded clinical trial.

BACKGROUND: Given the role of vitamin B6 on pronociceptive/antinociceptive neurotransmitters balance, metabolic reactions, and inflammation, it is important to clarify the effect of vitamin B6 on pain and psychological disturbance in fibromyalgia (FM). This study aimed to evaluate whether an 80-mg daily dose of vitamin B6 improves pain, disease severity and psychological symptoms of FM compared to a placebo. METHODS: This randomized, double-blinded, placebo-controlled trial was performed on the FM patients whose diagnosis was confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). 90 Patients were randomized to receive either vitamin B6 (80 mg daily) or placebo in a 1:1 ratio, with a permuted block size of 30 stratified by disease severity. Primary outcomes included the Revised Fibromyalgia Impact Questionnaire (FIQR), Hospital Anxiety and Depression Scale (HADS), 12-item short-form health survey (SF-12), and pain visual analog scale (pain-VAS)). The mean differences in outcomes (before and after treatment) were compared between the vitamin B6 and placebo groups using an independent T-test. An ANCOVA model adjusted for baseline outcome value was also provided to compare the outcomes between the two groups. RESULTS: Of 90 eligible patients, 60 patients (31 patients in vitamin B6 and 29 in the placebo group) completed the trial. Overall, the FIQR, pain-VAS, and HADS-anxiety scores improved after treatment in both vitamin B6 and placebo groups; However, there was no statistically significant intergroup difference regarding primary outcomes. ANCOVA model also showed no difference in the treatment effects. CONCLUSIONS: Our results showed no priority for vitamin B6 over placebo in FM patients. Considering the potential ameliorating role of vitamin B6 on pain and psychological symptoms, acknowledgment of vitamin B6 as a relatively safe adjuvant treatment needs larger future studies. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT20200920048782N2 on 2021/10/04.

The impact of fibromyalgia on health status according to the types, demographic background and pain index.

OBJECTIVES: To compare fibromyalgia (FM) core symptoms, FM impact severity and health status between the recently defined type A and type B of fibromyalgia. To compare disease impact and health status between FM patients and non-FM chronic pain control group. Finally, to compare health related quality of life and disease symptom severity by demographic background and widespread pain index (WPI). METHODS: A total of 284 consecutive FM patients and 96 non-FM control patients were enrolled. The information of four questionnaires including the Fibromyalgia Survey Questionnaire (FSQ), the Fibromyalgia Impact Questionnaire (FIQ), the 12-item Short Form Health Survey (SF-12) and questionnaires regarding demographic features were collected from a local FM registry. RESULTS: Of all FM patients, 102 (94%) and 7 (6%) were type A and B, respectively. We found statistically significant differences in symptomatology, the FIQ scores and the SF-12 subscales across two type and control groups (p<0.001). However, when we compared these scores pairwise, except WPI there were no significant differences in other scores between type A and B. Also, there were no significant differences in FIQ and SF-12 scores across different age or educational status groups. Interestingly, patients with higher WPI had significantly higher FIQ (overall, symptom, and total) scores, worse PCS-12 and MCS-12 scores, and vice versa. CONCLUSIONS: Type B constitutes a minor but important component of FM that probably has a marked impact on the patient's perceived illness severity and quality of life. Further, WPI probably is the most important single indicator of disease severity and quality of life in FM.

Correlation of invalidation with symptom severity and health status in fibromyalgia.

OBJECTIVE: Invalidation is a new construct in health psychology, especially in diseases with inherently invisible symptoms such as FM. It can potentially affect both the quality of life and disease severity in patients with FM. This study aimed to investigate the correlation of illness invalidation with health status and symptom severity in FM. METHODS: A total of 112 consecutive patients with FM referred to the rheumatology clinic were enrolled. Invalidation was measured by the Illness Invalidation Inventory (3*I). To measure patient status and progress of FM, the Revised Fibromyalgia Impact Questionnaire (FIQR) was used and patients' quality of life was assessed by the 12-item Short Form Health Survey (SF-12). Multiple linear regression analyses were performed and Spearman's correlations were calculated. RESULTS: All the patients were female and aged between 18 and 61 years. No significant differences in discounting and lack of understanding between various sources of invalidation were found. The strongest correlation was observed between FIQR symptom score and discounting by work (r = 0.519, P < 0.05). Multiple linear regression analyses revealed that only discounting from the spouse significantly predicted FIQR total scores of FM patients [P = 0.03 (CI 0.28, 10.64)]. CONCLUSION: Discounting correlated more strongly with SF-12 subscales and FIQR domains than did lack of understanding. The current study revealed that active negative social responses and the source of invalidation are important in predicting symptom severity and quality of life in FM.

Validation of fibromyalgia survey questionnaire and polysymptomatic distress scale in a Persian population.

The aim of this study was to assess validity of the fibromyalgia survey questionnaire (FSQ) and polysymptomatic distress scale (PSD) in an Iranian population. We also sought to classify the severity levels of fibromyalgia (FM) symptoms according to the PSD scale. Participants were divided into FM and non-FM chronic pain disorder groups according to expert physician diagnosis. Patients in both groups answered to Persian-translated version of FSQ, fibromyalgia impact questionnaire (FIQ) and Short-Form-12 (SF-12). Both 1990 ACR criteria and FSDC were assessed in participates of two groups. Internal consistency and construct validity were evaluated. There was good internal consistency measured by Cronbach's alpha (0.814 for FSQ). FSQ and its subscales correlated significantly with FIQ scores and SF-12 subscales, indicating acceptable construct validity. The concordance rates of FSQ with 1990 ACR criteria and expert diagnosis were 61.2 and 75.7, respectively (convergence validity). The mean score of PSD and its components in FM group were significantly more than in control groups (discriminative validity). Using lower PSD score cutoff (≥8.5) for the diagnosis of fibromyalgia appeared to be the most effective approach in our population. ROC analysis of the PSD scores revealed 8.5-11.5, 11.5-15 and more than 15, respectively, as a mild, moderate and severe FM. Persian version of FSQ was a valid instrument for application in survey research among Iranian patients with chronic pain disorders. The current study revealed that PSD could be used as a valid tool for assessment of symptoms intensity regardless of fibromyalgia diagnosis.

The validity and reliability of the Persian version of the Revised Fibromyalgia Impact Questionnaire.

The Revised Fibromyalgia Impact Questionnaire (FIQR), an updated version of the Fibromyalgia Impact Questionnaire (FIQ) achieved a better balance among different domains (i.e., function, overall impact, and symptom severity) and attempts to address the limitations of FIQ. As there is no Persian version of the FIQR available, we aimed to investigate the validity and reliability of a Persian translation of the FIQR in Iranian patients. After translating the FIQR into Persian, it was administered to 77 female patients with fibromyalgia syndrome. All of the patients filled out the questionnaire together with a Persian version of the FIQ, short form-12 (SF-12). The tender-point count was also calculated. One week later, FM patients filled out the Persian FIQR at their second visit. Reliability was analyzed by internal consistency and reproducibility including Cronbach's α coefficient and intra-class correlation coefficient. Construct validity was evaluated by Spearman's correlation coefficient and Pearson's correlation coefficient. Statistical analysis was performed using SPSS for Windows version 17.0. All patients included in this study were female, and the mean age was 38.23 ± 10.68 years. The total scores of the FIQR and FIQ were 49.77 ± 18.27 and 54.05 ± 14.00 that were closely correlated (r = 0.63, p < 0.01), and each of the three domains of the Persian FIQR was also correlated well with the three related FIQ domains (r = 0.36-0.63, p < 0.01). Also some significant inverse correlations of FIQR with quality-of-life (assessed by SF-12) domains and items were found. Cronbach's α was 0.87 for FIQR in the first visit. The Persian FIQR showed adequate reliability and validity. This instrument can be used in the clinical evaluation of Iranian patients with fibromyalgia.

Validation of the 2010 American College of Rheumatology preliminary diagnostic criteria for fibromyalgia in an Iranian population.

The aim of this study was to validate the 2010 American College of Rheumatology (ACR) preliminary criteria for fibromyalgia (FM) in an Iranian population. In this multicenter prospective study, we enrolled 168 FM patients and 110 controls. All participants underwent dolorimetry examination by study assessors and completed a questionnaire containing variables of both the ACR 2010 preliminary and ACR 1990 criteria. We compared the performance of the ACR 2010 criteria with the expert diagnosis as well as the ACR 1990 criteria. Receiver operator characteristic analyses and Youden index were used to evaluate the test characteristics of a set of different cutoff points for two subcomponents of ACR 2010 criteria including widespread pain index (WPI) and symptom severity (SS) scale. Considering expert diagnosis as the gold standard, the ACR 2010 criteria showed comparable specificity with ACR 1990 (92.8 vs. 88.3 %, P = 0.073), but lower sensitivity (58.9 vs. 71.4 %, P = 0.003) and a tendency for lower accuracy (72.4 vs. 78.4 %, P = 0.105). Applying the ACR 1990 criteria as the gold standard, we observed a trend toward an increase in overall accuracy (72.4 vs. 79.1 %, P = 0.064). Optimal test characteristics were achieved for WPI ≥6 and SS scale score ≥4 and improved sensitivity and accuracy of ACR 2010 criteria when compared to expert, 76.1 and 81.7, respectively. The preliminary ACR 2010 criteria performed less desirably in terms of sensitivity in our set of Iranian patients. Selecting lower cutoff points as WPI ≥6 and SS scale score ≥4 improved the diagnostic values of the criteria.

The crosstalk of the pathophysiologic models in fibromyalgia.

Fibromyalgia (FM) is a heterogeneous condition with various mechanisms (endotype) and manifestations (phenotypes). Many worthy endeavors have been dedicated to exploring the main trajectories of FM pathogenesis, depicted as the models of FM development. The Imbalance of Threat and Soothing Systems (FITSS) model, which is an advancing psychosocial form of the "central sensitization" model, and autonomic nervous system (ANS) model, besides new discoveries of potential pathways for FM development such as autoimmunity, small fiber pathology, and gut-brain axis currently comprise all our knowledge assets about FM pathogenesis. The pathophysiology of fibromyalgia is too complex to justify with one model, one main loop of pathogenesis, and one terminator. It appears that the variable FM models could justify some phenotypes of FM. Currently, our knowledge about FM pathogenesis and trying to match the different pathways and links mimic solving a puzzle in the hands of beginners. Until unraveling many missed interconnections and formulas between numerous scrambled pieces of the FM puzzle, proposing an integrated model seems not possible. This review focuses on the main trajectories of FM pathogenesis proposed thus far and tries to illuminate the crosstalking between them. We also propose the subgrouping FM into more homogenous categories based on the endotype-phenotype characteristics. It could provide a more pragmatic approach toward understanding of the diverse network of FM pathogenesis as well as the personalized stratification of FM. Key Points • The disentangled nature of FM pathogenesis escapes from embracing under one integrated model. • There appears to be no way for formulizing FM pathogenesis except the acknowledgment of the different pathways and their crosstalk explored as yet. • Acknowledging the different endotypes/phenotypes of FM spectrum and classifying them into more homogenous groups can help to the pragmatic approach to FM.

Association between neutrophil/lymphocyte ratio and disease severity in scleroderma patients.

Introduction: Systemic sclerosis is a chronic and progressive connective tissue disease with various manifestation. Inflammatory status is developed in early stages and is followed by major organs' dysfunction. Disease severity is evaluated mostly through Medsger scale. There is not any single laboratory test to evaluate disease severity, although some hematologic can reflect disease severity. In this study, we evaluated the association between hematologic indices (specially Neutrophil/Lymphocyte ratio) and Medsger score of disease severity. Materials and methods: One hundred and twenty-three patients along with the same number of healthy controls were enrolled in this study. Demographic information and past medical records were gathered in first appointment. Hematologic indices were calculated based on the laboratory findings and the association between these indices and Medsger score of disease severity was evaluated. Results: One hundred and twenty-three patients with mean disease duration of 9.54 and mean Medsger score of 7.42 were investigated in this study. Neutrophil count, erythrocyte sedimentation rate, red cell distribution width and NLR were significantly higher and mean platelets volume was significantly lower in SSc patients in comparison to controls. NLR was significantly correlated with pulmonary and cardiac involvements and Monocyte/Lymphocyte ratio was significantly correlated with the involvement of joint and tendons. We showed that NLR is a predictive factor for the severity of systemic sclerosis. We also found a cut off Value of 1.9 for NLR as a predictor for disease severity in our patients. Conclusion: Our study shows that SSc and its severity is associated with some hematologic indices like NLR, MLR, platelets and hemoglobin. These indices can also specifically predict the involvement of some organs.

Nociplastic pain concept, a mechanistic basis for pragmatic approach to fibromyalgia.

Nociplastic pain (NP), as a mechanistic term, denotes pain arising from altered nociception without clear evidence of tissue or somatosensory damage. Fibromyalgia (FM), a prototypical NP condition, incorporates a broad continuum of phenotypes with a distinct neurobiological signature and shared NP attributes. The nociplastic concept may provide a new opportunity for early diagnosis of FM by identifying the characteristic NP features before a state of pain generalization and symptoms clustering. In this approach, even individual symptoms associated with NP features are worthy of attention to denote FM. It may provide a timely diagnosis of FM before clinical progression to a severe and hard-to-manage condition. Furthermore, collecting all various FM phenotypes under the nociplastic concept and not delimiting FM to the only typical presentation allows investigators to identify FM subgroups reflecting potentially distinct pathophysiologic mechanisms and biomarkers. This viewpoint can be served in future studies to develop individualized management. In this review, we postulate a novel approach to early FM diagnosis and management based on NP conceptualization and phenotype recognition. Key Points • FM as a NP condition represents overlapping clinical phenotypes and incomplete presentations especially in early stage of illness. • The mechanistic approach based on the NP features of FM can be implicated in the timely diagnosis and management of FM. • The NP-based approach to FM provides a broader viewpoint beyond FM delimitation to pain generalization and polysymptomatic complaints.

Implication of the Nociplastic Features for Clinical Diagnosis of Fibromyalgia: Development of the Preliminary Nociplastic-Based Fibromyalgia Features (NFF) Tool.

OBJECTIVE: Nociplastic concept incorporates a broad continuum of pain phenotypes shared with clinical peculiarity. This study aimed to develop and validate a diagnostic tool, the preliminary Nociplastic-based Fibromyalgia Features (NFF), to detect fibromyalgia (FM) in patients with chronic pain. METHODS: Items requiring yes or no responses and relating to the most relevant clinical nociplastic pain (NP) features of FM were compiled by a group of expert rheumatologists. The provisional list was tested in a prospective study on 185 consecutive patients with chronic pain (126 patients with FM and 59 patients with non-FM non-inflammatory chronic pain) diagnosed based on expert decision. Identification of the most discriminant combinations of items for FM and the calculation of their sensitivity and specificity were based on both univariate and multivariate (stepwise logistic regression) analyses. All participants were investigated through the final NFF, the 2011 American College of Rheumatology (ACR) criteria, and the 2016 ACR criteria. NFF performance was assessed with receiver operating characteristic curve analysis. RESULTS: Based on multivariate analyses, we retained only seven items in the final version of the NFF. A cut-off score of 4 (corresponding to the number of positive items) gave the highest rate of correct identification of patients (85%), with a sensitivity of 82% and a specificity of 91%. The NFF showed the highest concordance rate with expert diagnosis (85%) and the lowest value (77%) with the ACR 2016 criteria. CONCLUSION: The preliminary NFF with respect to the various aspects of NP showed good performance for detection of the FM in the clinical setting. This tool may provide a more pragmatic approach to the timely diagnosis of FM.

Validity and reliability of the Persian version of illness invalidation inventory (3*I) among patients with non-inflammatory rheumatic painful disorders.

BACKGROUND: The Invalidation Illness Inventory (3*I) is an instrument that assesses invalidation (including discounting and lack of understanding dimensions) experienced by patients with rheumatic disorders. This study aimed to translate and validate the 3*I in Iran. METHODS: Following translation of the 3*I into the Iranian language (Persian), a cross-sectional study was conducted. A consecutive sample of females with chronic non-inflammatory rheumatic painful diseases completed the questionnaire. Patients also completed the Revised Symptom Impact Questionnaire (SIQR) and the Short Form Health Survey-12 (SF-12). To examine convergent validity, the correlation between the 3*I, the SIQR, and the SF-12 was assessed. The reliability of the 3*I was examined by internal consistency (the Cronbach's alpha coefficient) and intraclass correlation coefficient (ICC). RESULTS: In all 196 patients participated in the study. The mean (SD) age of patients was 45.62 ± 10.70 years. Several significant correlations between the Invalidation Illness Inventory (discounting/lack of understanding) with the symptom impact (SIQR) and the short form health survey (SF-12) were observed lending support to the convergent validity of the 3*I. The Cronbach's alpha coefficients were acceptable for most dimensions and sources, ranging from 0.52 to 0.88. Most ICC values for the dimensions of 3*I were above 0.75. CONCLUSIONS: The findings indicated that the Persian version of Illness Invalidation Inventory (3*I) is a valid instrument for invalidation assessment in patients with chronic pain. Given the high frequency of perceived invalidation among patients with rheumatic painful disorders, serious attention is needed to the issue in clinical and research settings.

No effect of approved fibromyalgia drugs on the social pain (invalidation) contrary to physical pain: an open-label short-term randomized clinical trial.

OBJECTIVES: The social pain or invalidation denoting painful feeling following social conflicts or misunderstanding about illness legitimacy has been proposed as a salient disabling symptom besides physical pain or non-pain symptoms in fibromyalgia (FM). We sought to evaluate the effect of 1-month administration of duloxetine or pregabalin on the invalidation dimensions in FM patients with respect to the comparison of these two drugs on this issue. METHOD: This open-label randomized clinical trial study was performed on FM patients whose diagnoses were confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). Primary outcome measure (Illness Invalidation Inventory (3*I)) and secondary outcome measures (Beck Depression Inventory-II (BDI-II), widespread pain index (WPI), and polysymptomatic distress scale (PSD)) were compared before and after treatment, using paired t test or Wilcoxon signed test. RESULTS: Of 81 eligible FM patients, 44 patients in the duloxetine arm and 27 patients in the pregabalin arm completed the study protocol. Overall, no significant improvement was seen in 3*I scores after treatment with either duloxetine or pregabalin, except in the lack of understanding of medical professionals which improved after treatment with pregabalin (2.43 ± 1.38 to 1.79 ± 0.94, p value: 0.01). There were no intragroup and intergroup differences in the effects of duloxetine and pregabalin on 3*I scores when adjusted with the cofounders. Both duloxetine and pregabalin improved WPI, BDI-II, and PSD scores significantly. CONCLUSIONS: Short-term FM pharmacological treatment had no effect on social pain. This finding was regardless of drug type, improvement of physical pain, and depression.

Effect of vitamin B12 on the symptom severity and psychological profile of fibromyalgia patients; a prospective pre-post study.

BACKGROUND: Fibromyalgia (FM) as a prototypical nociplastic pain condition displays a difficult therapeutic situation in many cases. Given the promising data on the effect of vitamin B12 in improving pain and cognitive functions in various nociplastic pain conditions, we aimed to determine the efficacy of 1000 mcg daily dose of oral vitamin B12 on the symptom severity and psychological profile of FM patients. METHODS: This open-label, pre-post study was performed on FM patients whose diagnoses were confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). Patients were instructed to take a daily dose of 1000mcg vitamin B12 for fifty days. Outcome measures including the Revised Fibromyalgia Impact Questionnaire (FIQR), Hospital Anxiety and Depression Scale (HADS), 12-item Short-Form health survey (SF-12), and pain Visual Analog Scale (pain-VAS) were fulfilled by patients before and after the treatment. RESULTS: Of 30 eligible patients, 28 patients completed the study protocol. Patients were female with a mean age of 47.50 ± 8.47 years. FIQR scores in all domains improved significantly after treatment (total FIQR: 49.8 ± 21.86 vs 40.00 ± 18.36, p value < 0.01; function: 13.17 ± 7.33 vs 10.30 ± 5.84, p value: 0.01; overall: 10.32 ± 6.22 vs 8.25 ± 6.22, p value: 0.03; symptoms: 26.30 ± 10.39 vs 21.44 ± 8.58, p value < 0.01). Vitamin B12 also improved anxiety scores from 9.33 ± 4.30 to 7.70 ± 3.60, p value: 0.01. Depression, pain-VAS, and SF-12 didn't improve following the treatment. The Generalized estimating equations (GEE) analysis showed the improvement in total FIQR score is not cofounded by the improvement of anxiety and patients' baseline characteristics. CONCLUSIONS: This study showed a short course of sublingual vitamin B12, 1000 mcg daily, significantly improves the severity of FM and anxiety score. We postulate that vitamin B12 has a strong potential to consider, at least, as adjunctive therapy of FM. TRIAL REGISTRATION: The study protocol was approved by the ethics committee of Guilan University of Medical Sciences (IR.GUMS.REC.1400.197) in accordance with the World Medical Association's code of ethics (Declaration of Helsinki, revised in Brazil 2013), and registered at an ICMJE and WHO recognized registry of clinical trials ( www.irct.ir ) on 28/08/2021 (registration number: IRCT20200920048782N1).

Two sides on the fibromyalgia coin: physical pain and social pain (invalidation).

Although fibromyalgia (FM) has been traditionally defined by the extent of physical pain sites alongside other non-pain symptoms, recent evidence has highlighted the importance of social dimension in definition of pain perception. Social pain or invalidation, which denotes painful feeling following social conflicts or misunderstanding about illness legitimacy, is an important but ignored issue in the FM lexicon. While physical and social pain seem to be different and separate entities, we hypothesize that they are completely intertwined with indistinct borders in FM. Accumulating emergent neuroscience and behavioral evidence highlights the overlapping of physical and social pain in different painful conditions. However, this overlapping seems to reach its maximum in FM. This review sheds more light on the tight interconnectivity between physical and social pain in FM from the perspective of intuitional commonalities, clinical aspects, and shared neural pathways. The conceptualization of FM as an integrative physical-social pain paradigm will move us closer to necessitating the incorporation of social pain in future models of FM diagnosis and management. Key Points • Considering of social pain as one key concept is relatively mute in FM literature. • Overlapping of physical and social pain seems to be unique in FM due to its nature. • Acknowledging social pain in the FM lexicon could shift the paradigm of diagnosis and management of FM patients.

Implication of invalidation concept in fibromyalgia diagnosis.

OBJECTIVES: The invalidation or social pain is an important but neglected issue in polysymptomatology of fibromyalgia (FM). This study sought whether tracing-perceived invalidation could be effective to discriminate between the presence and absence of FM in chronic pain patients with respect to five different sources, including spouses, family, colleagues, health professionals, and social services. METHODS: A total of 207 consecutive chronic pain patients were evaluated for the presence of FM by rheumatologic assessment. Invalidation was measured by the Illness Invalidation Inventory (3*I). Receiver operator characteristic (ROC) analyses were used to evaluate the ability of 3*I dimensions and sources to discriminate having FM among chronic pain patients. Binary logistic regression analyses were performed. RESULTS: The perceived discounting and lack of understanding from spouse and family sources were higher in FM rather than non-FM patients. ROC analyses demonstrated that invalidation dimensions stemming from spouse and family could appropriately discriminate between the presence and absence of FM. The area under the curve (AUC) for other sources showed non-significant values. Adjusted logistic regression analysis by age, education level, and work status showed that discounting by family and lack of understanding by the spouse could be significant predictors of FM (OR 2.30; 95% CI 1.29-4.11, P = 0.005; OR 1.72; 95% CI 1.08-2.74, P = 0.022, respectively). CONCLUSIONS: This study elucidated the discriminatory power of invalidation in identification of FM from non-FM patients, especially when originated from spouse and family. Our results provide a basis to propose the invalidation as a salient component in the FM dictionary parallel to other famous FM symptoms. Key Points • The incorporation of newly highlighted social definition of pain seems warranted in the pain practice. • Despite proposing invalidation in painful conditions, its diagnostic role in FM remains unexplored. • Acknowledging of invalidation or social pain in polysymptomatology of FM could shift the paradigm of diagnosis of FM.

Common MEFV mutation analysis in 36 Iranian patients with familial Mediterranean fever: clinical and demographic significance.

The aim of our study was to determine the spectrum of the 12 most common familial Mediterranean fever gene (MEFV) mutations in Iranian patients with heterogeneous ethnicity, using the familial Mediterranean fever (FMF) strip assay test. A total of 36 patients were diagnosed according to established clinical criteria. Genomic DNA from all patients was tested for 12 common mutations located in exon 2 (E148Q), 3 (P369S), 5 (F479L), 10 [M680I (G>C), M680I (G>A), I692del, M694V, M694I, K695R, V726A, A744S, R761H], respectively, using the FMF strip assay test. Of the 35 patients with mutations, ten were homozygote, 20 were compound heterozygote, and five were heterozygote. The most frequent genotype was M680I/M680I (6 patients, 16.7%). The most frequent mutation was M680I, followed by M694V, and V726A. The FMF strip assay test for common these 12 mutations was positive in 90.6% of alleles in this study, indicating that it appears to be an effective method for FMF mutation screening in Iranian patients.

Reliability of ACR criteria over time to differentiate classic fibromyalgia from nonspecific widespread pain syndrome: a 6-month prospective cohort study.

American College of Rheumatology (ACR) 1990 criteria, initially introduced to classify fibromyalgia (FM) syndrome, has gained popularity in research and clinical grounds for diagnostic purposes. The objectives of this study were designed to assess the consistency of ACR criteria against the time in classifying FM. This was a prospective cohort study performed in a multidisciplinary pain clinic from October 2002 to June 2005. Patients who were clinically suspected of having FM and had a normal screening laboratory evaluation were scheduled for dolorimetry. Those found to have 6 or more tender points were considered eligible and labeled as either classic or atypical FM if they did or did not, respectively, fulfil ACR criteria. The 2 groups were assessed using the Fibromyalgia Impact Questionnaire (FIQ) and compared using baseline characteristics. We reassessed dolorimetric exam and FIQ 6 months later. Of 91 patients who participated in this study,70 completed the follow-up. Of them, 34 (49%) patients were identified as atypical, and 36 (51%) were labeled as classic FM. At first visit, the classic FM group had higher scores on sleep quality, stiffness, anxiety, depression, and total FIQ score (p\0.05) but not for other variables. At 6 months, there was no significant difference between the 2 groups in all measured variables. Labeling shift from classic to atypical FM and vice versa occurred at a rate of 36.1 and 32.4%, respectively. This study showed the ACR 1990 criteria was not able to consistently classify affected patients with FM syndrome within a group of patients having nonspecific body pain and multiple tender points over 6 months of follow-up.

Comparing duloxetine and pregabalin for treatment of pain and depression in women with fibromyalgia: an open-label randomized clinical trial.

BACKGROUND: Duloxetine and pregabalin are among the most widely used medications in the treatment of patients with fibromyalgia syndrome (FM). OBJECTIVES: To add to the very few lines of evidence that exist on the comparative safety and efficacy of these two medications. METHODS: In this open-label randomized clinical trial, outpatient women, who were diagnosed with FM based on American College of Rheumatology 2010 criteria, and had an age range of 18-65 years old were assigned to either duloxetine 30-60 mg or pregabalin 75-150 mg per day for 4 weeks. Patients were excluded in cases of having used duloxetine, pregabalin, gabapentin, or antidepressants within 12 weeks prior to the study, having had a history of comorbid medical conditions that could provoke chronic pain, or having had comorbid neuropsychiatric disorders, except for major depressive/anxiety disorders. Primary outcomes were between-group differences in mean score changes from baseline to end point for Widespread Pain Index (WPI) and Beck Depression Inventory-II. Secondary outcomes were the same statistical estimates, but for Fibromyalgia Impact Questionnaire-Revised and 12-Item Short Form Survey. Descriptive statistics and independent samples t-test were the main methods of analysis. ( www.irct.ir ; IRCT2016030626935N1). RESULTS: Among all the scales, only WPI scores improved with a statistically significant difference between the two treatment arms, favoring duloxetine (Mean difference in score change - 2.32, 95% CI, -4.46 to - 0.18; p = 0.034; Cohen's d 0.53 95% CI, 0.04 to 1.02). Drop out rate and cumulative incidence of nausea was significantly higher in the duloxetine arm compared to the pregabalin arm. CONCLUSION: This study provides further evidence on higher efficacy of duloxetine compared to pregabalin for the treatment of pain in patients with fibromyalgia. Future comprehensive pragmatic clinical trials are warranted.

Fibromyalgia diagnostic model derived from combination of American College of Rheumatology 1990 and 2011 criteria.

BACKGROUND: We aimed to explore the American College of Rheumatology (ACR) 1990 and 2011 fibromyalgia (FM) classification criteria's items and the components of Fibromyalgia Impact Questionnaire (FIQ) to identify features best discriminating FM features. Finally, we developed a combined FM diagnostic (C-FM) model using the FM's key features. METHODS: The means and frequency on tender points (TPs), ACR 2011 components and FIQ items were calculated in the FM and non-FM (osteoarthritis [OA] and non-OA) patients. Then, two-step multiple logistic regression analysis was performed to order these variables according to their maximal statistical contribution in predicting group membership. Partial correlations assessed their unique contribution, and two-group discriminant analysis provided a classification table. Using receiver operator characteristic analyses, we determined the sensitivity and specificity of the final model. RESULTS: A total of 172 patients with FM, 75 with OA and 21 with periarthritis or regional pain syndromes were enrolled. Two steps multiple logistic regression analysis identified 8 key features of FM which accounted for 64.8% of variance associated with FM group membership: lateral epicondyle TP with variance percentages (36.9%), neck pain (14.5%), fatigue (4.7%), insomnia (3%), upper back pain (2.2%), shoulder pain (1.5%), gluteal TP (1.2%), and FIQ fatigue (0.9%). The C-FM model demonstrated a 91.4% correct classification rate, 91.9% for sensitivity and 91.7% for specificity. CONCLUSIONS: The C-FM model can accurately detect FM patients among other pain disorders. Re-inclusion of TPs along with saving of FM main symptoms in the C-FM model is a unique feature of this model.