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.

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 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.

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.