Association of OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 polymorphisms with clinical phenotype among women with fibromyalgia.

To investigate the association between three selected pain polymorphisms and clinical, functional, sensory-related, psychophysical, psychological or cognitive variables in a sample of women with fibromyalgia (FMS). One hundred twenty-three (n = 123) women with FMS completed demographic (age, height, weight), clinical (years with pain, intensity of pain at rest and during daily living activities), functional (quality of life, physical function), sensory-related (sensitization-associated and neuropathic-associated symptoms), psychophysical (pressure pain thresholds), psychological (sleep quality, depressive and anxiety level) and cognitive (pain catastrophizing, kinesiophobia) variables. Those three genotypes of the OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 single nucleotide polymorphisms were obtained by polymerase chain reactions from no-stimulated whole saliva collection. No significant differences in demographic, clinical, functional, sensory-related, psychophysical, psychological and cognitive variables according to OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680 genotype were identified in our sample of women with FMS. A multilevel analysis did not either reveal any significant gene-to-gene interaction between OPRM1 rs1799971 x HTR1B rs6296, OPRM1 rs1799971 x COMT rs4680 and HTR1B rs6296 x COMT rs4680 for any of the investigated outcomes. This study revealed that three single nucleotide polymorphisms, OPRM1 rs1799971, HTR1B rs6296 or COMT rs4680, mostly associated with chronic pain were not involved in phenotyping features of FMS. Potential gene-to-gene interaction and their association with clinical phenotype in women with FMS should be further investigated in future studies including large sample sizes.

Minimal Clinically Important Differences in Hand Pain Intensity (Numerical Pain Rate Scale) and Related-Function (Boston Carpal Tunnel Questionnaire) in Women With Carpal Tunnel Syndrome.

OBJECTIVE: To calculate the minimal clinically important differences (MCIDs) for hand pain intensity and the Boston Carpal Tunnel Questionnaire (BCTQ) in a sample of women with carpal tunnel syndrome (CTS). DESIGN: Secondary analysis of a randomized controlled trial. SETTING: A Hospital Rehabilitation Unit. PARTICIPANTS: One hundred twenty women with clinical and electromyographic diagnosis of CTS who were randomly assigned into 2 groups (N=120). INTERVENTIONS: One group received 3 sessions of manual physical therapy (n=60) and the other group received surgery (n=60). MAIN OUTCOME MEASURES: Mean and the worst pain intensity (numerical pain rate scale, 0-10 points) and functional status and symptoms' severity subscales of the BCTQ questionnaire were assessed before and 1 month after treatment. The Global Rating of Change (GROC) was used as the anchor variable for determining the MCID. RESULTS: A change of 1.5 and 2.5 points in mean and the worst pain intensity represents the MCID for Numerical Pain Rating Scale, whereas a change of 0.23 and 0.64 points in functional status and symptoms' severity represents the MCID for each subscale of the BCTQ. All variables showed acceptable discrimination between patients classified as "improved" and those classified as "stable/not improved" (area under the curve≥0.72). Mean pain intensity (Youden index, 0.53; sensitivity: 73.3%; specificity: 80%) and symptoms' severity (Youden index, 0.69; sensitivity: 90%; specificity: 77.8%) showed the best discriminative ability expressed as a percentage of prediction. Participants classified as "improved" had significantly greater improvements in pain intensity, functional status, and symptoms' severity compared with those classified as "stable/not improved". CONCLUSION: A change of 1.5 and 2.5 points in mean and the worst pain and a change of 0.23 and 0.64 points in functional status and symptoms' severity represents the MCID for pain intensity and BCTQ in women with CTS 1 month after treatment.

Clustering analysis identifies two subgroups of women with fibromyalgia with different psychological, cognitive, health-related, and physical features but similar widespread pressure pain sensitivity.

OBJECTIVE: Given that identification of groups of patients can help to better understand risk factors related to each group and to improve personalized therapeutic strategies, this study aimed to identify subgroups (clusters) of women with fibromyalgia syndrome (FMS) according to pain, pain-related disability, neurophysiological, cognitive, health, psychological, or physical features. METHODS: Demographic, pain, sensory, pain-related disability, psychological, health, cognitive, and physical variables were collected in 113 women with FMS. Widespread pressure pain thresholds were also assessed. K-means clustering was used to identify groups of women without any previous assumption. RESULTS: Two clusters exhibiting similar widespread sensitivity to pressure pain (pressure pain thresholds) but differing in the remaining variables were identified. Overall, women in one cluster exhibited higher pain intensity and pain-related disability; more sensitization-associated and neuropathic pain symptoms; higher kinesiophobia, hypervigilance, and catastrophism levels; worse sleep quality; higher anxiety/depressive levels; lower health-related function; and worse physical function than women in the other cluster. CONCLUSIONS: Cluster analysis identified one group of women with FMS exhibiting worse sensory, psychological, cognitive, and health-related features. Widespread sensitivity to pressure pain seems to be a common feature of FMS. The present results suggest that this group of women with FMS might need to be treated differently.

Understanding the Psychophysiological and Sensitization Mechanisms Behind Fibromyalgia Syndrome: A Network Analysis Approach.

OBJECTIVE: Current evidence suggests that fibromyalgia syndrome (FMS) involves complex underlying mechanisms. This study aimed to quantify the multivariate relationships between clinical, psychophysical, and psychological outcomes in women with FMS by using network analysis to understand the psychobiological mechanisms driving FMS and generating new research questions for improving treatment strategies. METHODS: Demographic (age, height, weight), clinical (pain history, pain intensity at rest and during daily living activities), psychophysical (widespread pressure pain thresholds [PPT]), sensory-related (PainDETECT, S-LANSS, Central Sensitization Inventory [CSI]) and psychological (depressive and anxiety levels) variables were collected in 126 women with FMS. Network analysis was conducted to quantify the adjusted correlations between the modeled variables and to assess their centrality indices (i.e., the connectivity with other symptoms in the network and the importance in the system modelled as network). RESULTS: The network showed several local associations between psychophysical and clinical sensory-related variables. Multiple positive correlations between PPTs were observed, being the strongest weight between PPTs on the knee and tibialis anterior muscle (ρ: 0.33). PainDETECT was associated with LANSS (ρ: 0.45) and CSI (ρ: 0.24), whereas CSI was associated with HADS-A (ρ: 0.28). The most central variables were PPTs over the tibialis anterior (the highest Strength centrality) and CSI (the highest Closeness and Betweenness centrality). CONCLUSION: Our findings support a model where clinical sensory-related, psychological, and psycho-physical variables are connected, albeit in separate clusters, reflecting a nociplastic condition with a relevant role of sensitization. Clinical implications of the findings, such as developing treatments targeting these mechanisms, are discussed.

Efficacy of Dry Needling and Acupuncture in Patients with Fibromyalgia: A Systematic Review and Meta-Analysis.

Fibromyalgia (FM) is a syndrome that involves chronic pain, fatigue, sleep disturbance and impaired quality of life and daily functioning. In addition to medical and psychological therapies, other therapies including acupuncture and dry needling aim to reduce pain and disability in patients with FM. The aim of this study was to investigate the efficacy of dry needling and acupuncture in patients with FM regarding pain, function and disability in both the short and the long term. MEDLINE, PubMed, SCOPUS and Web of Science databases were systematically searched for randomized controlled trial studies evaluating efficacy data of dry needling or/and acupuncture treatments to improve pain, fatigue, sleep disturbance and impaired quality of life and/or daily function. A qualitative analysis including the methodological quality and a systematic data synthesis was performed. A total of 25 studies addressed the selection criteria. Most studies had an acceptable methodological quality. Four studies assessed the effect of dry needling, and twenty-one studies assessed the effect of acupuncture. In general, both interventions improved pain, anxiety, depression, fatigue, stiffness, quality of sleep and quality of life. However, both techniques were not compared in any study. Acupuncture and dry needling therapies seems to be effective in patients with FM, since both reduced pain pressure thresholds, anxiety, depression, fatigue, sleep disturbances and disability in the short term. It is still required to compare both techniques and their application in the long term.

Network Analysis for Better Understanding the Complex Psycho-Biological Mechanisms behind Fibromyalgia Syndrome.

The aim of this study was to assess potential associations between sensory, cognitive, health-related, and physical variables in women with fibromyalgia syndrome (FMS) using a network analysis for better understanding the complexity of psycho-biological mechanisms. Demographic, clinical, pressure pain threshold (PPT), health-related, physical, and psychological/cognitive variables were collected in 126 women with FMS. A network analysis was conducted to quantify the adjusted correlations between the modeled variables and to assess the centrality indices (i.e., the degree of connection with other symptoms in the network and the importance in the system modeled as a network. This model showed several local associations between the variables. Multiple positive correlations between PPTs were observed, being the strongest weight between PPTs over the knee and tibialis anterior (ρ: 0.28). Catastrophism was associated with higher hypervigilance (ρ: 0.23) and lower health-related EuroQol-5D (ρ: −0.24). The most central variables were PPT over the tibialis anterior (the highest strength centrality), hand grip (the highest harmonic centrality) and Time Up and Go (the highest betweenness centrality). This study, applying network analysis to understand the complex mechanisms of women with FMS, supports a model where sensory-related, psychological/cognitive, health-related, and physical variables are connected. Implications of the current findings, e.g., developing treatments targeting these mechanisms, are discussed.

Convergent validity of the central sensitization inventory in women with fibromyalgia: Association with clinical, psychological and psychophysical outcomes.

BACKGROUND: To assess the relationship between demographic, clinical, psychological and pressure pain sensitivity outcomes with the central sensitization inventory (CSI) in female with fibromyalgia (FMS). METHODS: One hundred and twenty-six (n = 126) females with FMS completed demographic (age, body mass index, height, weight), clinical (pain history, pain intensity at rest and during daily living activities), psychological (depression/anxiety levels) outcomes and widespread pressure pain sensitivity as well as the central sensitization inventory (CSI). After conducting a multivariable correlation analysis to identify the association between variables, a multiple linear regression model was performed to identify CSI predictors. RESULTS: The CSI was negatively associated with age (r = -0.262) and PPTs (r ranged from -0.221 to -0.372) and positively associated with anxiety (r = 0.541), depression (r = 0.415), mean intensity (r = 0.305), worst pain (r = 0.249) and pain during daily living activities (r = 0.398). The stepwise regression analysis revealed that 47.4% of CSI variance in this sample was explained by anxiety levels (27.8%), PPT at greater trochanter (10.5%), age (1.4%), years with pain (4.8%) and pain during daily living activities (2.9%). CONCLUSION: The current study found that age, pain intensity at rest and pain during daily living activities, anxiety levels and pressure pain sensitivity are associated with the CSI (associated sensitization symptoms) in women with FMS. SIGNIFICANCE: This study found that sensitization-associated symptoms in women with FMS are partially influenced by age, pain intensity at rest and pain during daily living activities, anxiety levels and pressure pain sensitivity.

The Prevalence of Shoulder Disorders among Professional Bullfighters: A Cross-Sectional Ultrasonography Study.

We aimed to investigate clinical and ultrasound signs of shoulder overuse injuries in professional bullfighters; side-to-side differences (dominant vs. non-dominant); and to determine potential differences according to bullfighters' categories. An observational cross-sectional study was conducted. Thirty professional and active bullfighters were assessed. A bilateral ultrasound assessment of the subacromial bursa, long biceps head tendon (LHBT), and rotator cuff was performed to determine the presence of bursitis, subluxation, partial or total tendon rupture, tenosynovitis, or calcification. Supraspinatus tendon thickness was measured. Finally, a battery of clinical orthopedic tests (Yergason, Jobe, infraspinatus, Gerber, and bursa tests) were also performed. Most identified ultrasound findings were located in the dominant side, being the presence of bursitis (n = 9; 30%), LHBT tenosynovitis (n = 8; 26.7%), and subscapularis tendon calcification (n = 5; 16.7%) the most prevalent. No side-to-side or between-categories differences were found for supraspinatus tendon thickness (all, p > 0.05). The most frequent positive signs were the infraspinatus test (40.0%), Gerber lift-off test (33.3%), and bursitis, Jobe, and Yergason tests (all, 26.7%). Ultrasound signs were commonly found at LHBT, subacromial bursa, and rotator cuff in professional bullfighters without difference between categories and sides. No side-to-side or between-categories differences were found. Positive clinical test signs suggestive of bursitis, LHBT, and rotator cuff tendinopathy were frequently observed.

Distress and Sensitization as Main Mediators of Severity in Women with Fibromyalgia: A Structural Equation Model.

We aimed to explore a path model identified using a structural equation model (SEM) which best explains the multivariate contributions of sensitization, sensitivity, and emotional variables to clinical severity in women with FMS. Pain features, the Central Sensitization Inventory (CSI), painDETECT, S-LANSS, the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index (PSQI), the Pain Catastrophizing Scale (PCS), the Pain Vigilance and Awareness Questionnaire (PVAQ), the 11-item Tampa Scale for Kinesiophobia (TSK-11), and pressure pain thresholds (PPTs) were collected from 113 women with FMS. Four latent variables were created: severity (clinical pain features), sensitivity (PPTs), sensitization (S-LANSS, CSI, painDETECT), and distress (HADS-A, HADS-D, PCS, PVAQ, TSK-11). Data fit for the measurement model were considered excellent (RMSEA = 0.043, CFI = 0.966, SRMR = 0.067, and NNFI = 0.960). Distress had a significant relationship with the mediators of sleep (ß = 0.452, p = 0.031) and sensitization (ß = 0.618, p = 0.001). The only mediator with a significant effect (ß = 1.113, p < 0.001) on severity was sensitization. A significant indirect effect of sensitization (ß = 0.687, p = 0.001) that explained the relationship between distress and severity was also identified. The proposed model suggests that distress and sensitization, together with poor sleep, have a complex mediating effect on severity in women with FMS. The identified path model can be leveraged in clinical trials investigating treatment approaches for FMS.

The hand grip force test as a measure of physical function in women with fibromyalgia.

Previous studies have reported the presence of muscle weakness in women with fibromyalgia syndrome (FMS) which is considered a risk factor for developing earlier disability and dependence during activities of daily life (ADL). We aimed to assess the relationship between hand grip force with sociodemographic, clinical, disease-specific, cognitive, and physical function variables in women with FMS. One hundred twenty-six women with FMS completed demographic (age, gender, height, weight, body mass index), pain-related (pain history, pain intensity at rest and during ADL), disease-specific severity (Fibromyalgia Impact Questionnaire -FIQ-S-, Fibromyalgia Health Assessment Questionnaire -FHAQ-, EuroQol-5D, Pain Catastrophizing Scale -PCS-, Pittsburgh Sleep Quality Index-PSQI-, Pain Vigilance and Awareness Questionnaire -PVAQ-, and Central Sensitization Inventory -CSI-), psychological (Tampa Scale for Kinesiophobia, TKS-11; Pain Vigilance and Awareness Questionnaire, PVAQ; Pain Catastrophizing Scale, PCS), and physical function (hand grip force, and Timed Up and Go Test, TUG). Hand grip force was associated with height (r = -0.273), BMI (r = 0.265), worst pain at rest (r = -0.228), pain during ADL (r = -0.244), TUG (r = -0.406), FHAQ (r = -0.386), EuroQol-5D (r = 0.353), CSI (r = -0.321) and PSQI (r = -0.250). The stepwise regression analysis revealed that 34.4% of hand grip force was explained by weight (6.4%), TUG (22.2%), and FHAQ (5.8%) variables. This study found that hand grip force is associated with physical function indicators, but not with fear-avoidance behaviors nor pain-related features of FMS. Hand grip force could be considered as an easy tool for identifying the risk of fall and poorer physical health status.

Association of Neuropathic Pain Symptoms with Sensitization Related Symptomatology in Women with Fibromyalgia.

We aimed to analyze potential correlations between S-LANSS and PainDETECT with proxies for pain sensitization, e.g., the Central Sensitization Inventory (CSI) and pressure pain hyperalgesia (construct validity), pain-related or psychological variables (concurrent validity) in women with fibromyalgia (FMS). One-hundred-and-twenty-six females with FMS completed demographic, pain-related variables, psychological, and sensitization outcomes as well as the S-LANSS and the PainDETECT questionnaires. S-LANSS was positively associated with BMI (r = 0.206), pain intensity (r = 0.206 to 0.298) and CSI score (r = 0.336) and negatively associated with all PPTs (r = -0.180 to -0.336). PainDETECT was negatively associated with age (r = -0.272) and all PPTs (r = -0.226 to -0.378) and positively correlated with pain intensity (r = 0.258 to 0.439), CSI (r = 0.538), anxiety (r = 0.246) and depression (r = 0.258). 51.4% of the S-LANSS was explained by PainDETECT (45.3%), posterior iliac PPT (0.2%) and mastoid PPT (5.9%), whereas the 56.4% of PainDETECT was explained by S-LANSS (43.4%), CSI (10.4%), and pain intensity (2.6%). This study found good convergent association between S-LANSS and PainDETECT in women with FMS. Additionally, S-LANSS was associated with PPTs whereas PainDETECT was associated with pain intensity and CSI, suggesting that both questionnaires assess different spectrums of the neuropathic and pain sensitization components of a condition and hence provide synergistic information.

Cervical Multifidus Morphology and Quality Are Not Associated with Clinical Variables in Women with Fibromyalgia: An Observational Study.

OBJECTIVE: Some studies have reported the presence of histological alterations, such as myofiber disorganization and abnormalities in the number and shape of mitochondria, in patients with fibromyalgia syndrome (FMS). Although Ultrasound imaging (US) is used to quantitatively characterize muscle tissues, US studies in patients with FMS are lacking. Therefore, we aimed to describe morphological and qualitative cervical multifidus (CM) muscle US features in women with FMS and to assess their correlation with clinical indicators. DESIGN: Observational study. SETTING: AFINSYFACRO Fibromyalgia Association (Madrid, Spain). SUBJECTS: Forty-five women with FMS participated. METHODS: Sociodemographic variables (e.g., age, height, weight, body mass index) and clinical outcomes (e.g., pain as assessed on a numerical pain rating scale, evolution time, pain-related disability as assessed by the Fibromyalgia Impact Questionnaire) were collected. Images were acquired bilaterally at the cervical spine (C4-C5 level) and measured by an experienced examiner for assessment of muscle morphology (e.g., cross-sectional area, perimeter, and shape) and quality (mean echo intensity and intramuscular fatty infiltration). Side-to-side comparisons and a correlational analysis were conducted. RESULTS: No significant side-to-side differences were found for morphology or quality features (P > 0.05). None of the clinical indicators were associated with US characteristics (all, P > 0.05). CONCLUSION: Our results showed no side-to-side differences for CM morphology and quality as assessed with US. No associations between CM muscle morphology or quality and Fibromyalgia Impact Questionnaire, pressure pain threshold, numerical pain rating scale score, or evolution time were observed. Our preliminary data suggest that muscle morphology is not directly related to pain and pain-related disability in women with FMS.

Pain Intensity and Sensory Perception of Tender Points in Female Patients with Fibromyalgia: A Pilot Study.

Fibromyalgia syndrome (FMS) is a condition that courses with chronic pain, fatigue, sleep disturbance, impaired quality of life and daily function. Due to the lack of blood, imaging or histological confirmatory tests, the diagnosis of FMS is based on the presence of widespread pain and presence of tender points (TPs). Our aim was to assess the pain pressure thresholds (PPTs) and subjective pain perception (SPP) of all 18 TPs while applying a normalized pressure in female patients with fibromyalgia. An exploratory descriptive pilot study was conducted in 30 female patients with FMS. Sociodemographic data (e.g., age, height, weight, and body mass index), clinical characteristics (e.g., years with diagnosis and severity of FMS), PPTs (assessed with an algometer), and SPP (assessed with a visual analogue scale) of all 18 TPs were collected. A comparative analysis side-to-side (same TP, left and right sides) and between TPs was conducted. No side-to-side differences were found (p < 0.05). Significant differences between all 18 TPs were found for PPTs (p < 0.0001), and SPP (p < 0.005) scores were found. The most mechanosensitive points were located in the second costochondral junction, the occiput, the trochanteric prominence; the most painful while applying a normalized pressure considering the TP and side were those located in the gluteus, trochanteric prominence, and supraspinatus. The current study describes PPTs and SPP, as assessed with algometry and visual analogue scale, respectively, of all 18 TPs in female patients with FMS. TPs exhibited significant PPTs and SPP differences between TP locations with no side-to-side differences.

Pain and Cortisol in Patients with Fibromyalgia: Systematic Review and Meta-Analysis.

This systematic review and meta-analysis sought to gain further insight into the relationship between cortisol reactivity and chronic widespread pain in patients with fibromyalgia. The studies selected were those conducted in adults with fibromyalgia that were random controlled, non-controlled or observational. Studies were excluded if they examined diseases other than fibromyalgia or if they did not report on pain or cortisol. Twelve studies met inclusion criteria. Data were extracted into tabular format using predefined data fields by two reviewers and assessed for accuracy by a third reviewer. The methodological quality of the studies was assessed using the PEDro scale. Data Synthesis: Of 263 studies identified, 12 were selected for our review and 10 were finally included as their methodological quality was good. In the meta-analysis, we calculated effect sizes of interventions on pain indicators and cortisol levels in patients with fibromyalgia. A small overall effect of all the interventions was observed on pain tolerance and pressure pain thresholds, yet this effect lacked significance (ES = 0.150; 95%CI 0.932-1.550; p > 0.05). Conclusions: While some effects of individual nonpharmacological therapeutic interventions were observed on both cortisol levels and measures of pain, our results suggest much further work is needed to elucidate the true relationship between chronic widespread pain and cortisol levels in patients with fibromyalgia.