Evaluation of Cognitive Performance in Patients with Fibromyalgia Syndrome: A Case-Control Study.

Patients with fibromyalgia syndrome tend to report deficits in cognitive functions; however, there is no clear consensus on which cognitive domains are impaired. The aim of this study was to compare the differences in cognitive performance between a group of patients with fibromyalgia syndrome and a group of pain-free subjects controlling for the covariables anxiety, depression, and sleep quality. In total, 130 patients with fibromyalgia syndrome and 111 pain-free subjects with an average age of 54.96 years completed the evaluation protocol consisting of sociodemographic data, psychological data, and neurocognitive tests. All data were collected from May 2022 to May 2023. Multivariate analyses of covariance (MANCOVAs) were conducted to assess intergroup differences in all neurocognitive tests. MANCOVA analyses showed that the group of patients with fibromyalgia showed a worse cognitive performance than the group of pain-free subjects after controlling for anxiety, depression, and sleep quality. This study found that fibromyalgia patients exhibited worse cognitive performance and executive function than pain-free subjects. Thus, cognitive performance seems to not be related with anxiety, depression, or sleep quality in our sample of women with FMS.

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.

Prognostic Factors for Postoperative Chronic Pain after Knee or Hip Replacement in Patients with Knee or Hip Osteoarthritis: An Umbrella Review.

Knee and hip osteoarthritis are highly prevalent in the older population. Management of osteoarthritis-related pain includes conservative or surgical treatment. Although knee or hip joint replacement is associated with positive outcomes, up to 30% of patients report postoperative pain in the first two years. This study aimed to synthesize current evidence on prognostic factors for predicting postoperative pain after knee or hip replacement. An umbrella review of systematic reviews was conducted to summarize the magnitude and quality of the evidence for prognostic preoperative factors predictive of postoperative chronic pain (>6 months after surgery) in patients who had received knee or hip replacement. Searches were conducted in MEDLINE, CINAHL, PubMed, PEDro, SCOPUS, Cochrane Library, and Web of Science databases from inception up to 5 August 2022 for reviews published in the English language. A narrative synthesis, a risk of bias assessment, and an evaluation of the evidence confidence were performed. Eighteen reviews (nine on knee surgery, four on hip replacement, and seven on both hip/knee replacement) were included. From 44 potential preoperative prognostic factors, just 20 were judged as having high or moderate confidence for robust findings. Race, opioid use, preoperative function, neuropathic pain symptoms, pain catastrophizing, anxiety, other pain sites, fear of movement, social support, preoperative pain, mental health, coping strategies, central sensitization-associated symptoms, and depression had high/moderate confidence for an association with postoperative chronic pain. Some comorbidities such as heart disease, stroke, lung disease, nervous system disorders, and poor circulation had high/moderate confidence for no association with postoperative chronic pain. This review has identified multiple preoperative factors (i.e., sociodemographic, clinical, psychological, cognitive) associated with postoperative chronic pain after knee or hip replacement. These factors may be used for identifying individuals at a risk of developing postoperative chronic pain. Further research can investigate the impact of using such prognostic data on treatment decisions and patient outcomes.

Multidimensional evaluation of the pain profile as prognostic factor in individuals with hip or knee osteoarthritis receiving total joint replacement: protocol of a 2-year longitudinal prognostic cohort study.

INTRODUCTION: Knee and hip osteoarthritis are two highly prevalent musculoskeletal pain conditions. Unsuccessful rates after hip/knee replacement range from 10% to 20%. Subjects with sensitisation manifestations are vulnerable to worse clinical outcomes. Most studies have analysed outcomes up to 1 year after surgery. The aim of this 2-year longitudinal study will be to evaluate sensory-related, psychological and psychophysical pain sensitisation manifestations and a potential epigenetic biomarker as prognostic clinical outcomes for the development of chronic postoperative pain after knee or hip replacement. METHODS AND ANALYSIS: A prospective longitudinal study with a 2-year follow-up period will be conducted. The prognostic variables will include pain, function, related-disability, anxiety, depression, quality of life, sensitisation-associated symptoms, kinesiophobia, neuropathic pain and catastrophising, and expectative of the intervention will be assessed before surgery. We will also evaluate the presence of the Val158Met polymorphism as a possible epigenetic marker. Clinical outcomes including pain, related-disability and self-perceived satisfaction, sensitisation-associated symptoms and neuropathic pain will be assessed 3, 6, 12, 18 and 24 months after surgery. These variables will be used to construct three prediction models: (1) pain and function, (2) sensitisation-associated symptomatology and (3) neuropathic pain features classifying those patients in responders and non-responders. Data from knee or hip osteoarthritis will be analysed separately. Statistical analyses will be conducted with logistic regressions. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of both institutions involved (Hospital Universitario Fundación Alcorcón (HUFA) 19-141 and Universidad Rey Juan Carlos (URJC) 0312201917319). Participants will sign the written informed consent before their inclusion. Study results will be disseminated through peer-reviewed publications and presentations at scientific meetings.

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.

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.

Bayesian Linear Regressions Applied to Fibromyalgia Syndrome for Understanding the Complexity of This Disorder.

A better understanding of the connection between factors associated with pain sensitivity and related disability in people with fibromyalgia syndrome may assist therapists in optimizing therapeutic programs. The current study applied mathematical modeling to analyze relationships between pain-related, psychological, psychophysical, health-related, and cognitive variables with sensitization symptom and related disability by using Bayesian Linear Regressions (BLR) in women with fibromyalgia syndrome (FMS). The novelty of the present work was to transfer a mathematical background to a complex pain condition with widespread symptoms. Demographic, clinical, psychological, psychophysical, health-related, cognitive, sensory-related, and related-disability variables were collected in 126 women with FMS. The first BLR model revealed that age, pain intensity at rest (mean-worst pain), years with pain (history of pain), and anxiety levels have significant correlations with the presence of sensitization-associated symptoms. The second BLR showed that lower health-related quality of life and higher pain intensity at rest (mean-worst pain) and pain intensity with daily activities were significantly correlated with related disability. These results support an application of mathematical modeling for identifying different interactions between a sensory (i.e., Central Sensitization Score) and a functional (i.e., Fibromyalgia Impact Questionnaire) aspect in women with 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.

Muscle Trigger Points and Pressure Pain Sensitivity Maps of the Feet in Women with Fibromyalgia Syndrome.

OBJECTIVE : To investigate the presence of trigger points (TrPs) in feet musculature and topographical pressure sensitivity maps of the feet as well as the relationship between TrPs, pressure pain maps, and clinical variables in women with fibromyalgia (FMS). METHODS : Fifty-one FMS women and 24 comparable healthy women participated. TrPs within the flexor hallucis brevis, adductor hallucis, dorsal interossei, extensor digitorum brevis, and quadratus plantae, as well as external and internal gastrocnemius, were explored. Pressure pain thresholds (PPTs) were assessed in a blind manner over seven locations on each foot. Topographical pressure sensitivity maps of the plantar region were generated using the averaged PPT of each location. RESULTS : The prevalence rate of foot pain was 63% (n = 32). The number of active TrPs for each FMS woman with foot pain was 5 ± 1.5 without any latent TrPs. Women with FMS without foot pain and healthy controls had only latent TrPs (2.2 ± 0.8 and 1.5 ± 1.3, respectively). Active TrPs in the flexor hallucis brevis and adductor hallucis muscles were the most prevalent. Topographical pressure pain sensitivity maps revealed that FMS women with foot pain had lower PPT than FMS women without pain and healthy controls, and higher PPT on the calcaneus bone (P < 0.001). CONCLUSIONS : The presence of foot pain in women with FMS is high. The referred pain elicited by active TrPs in the foot muscles reproduced the symptoms in these patients. FMS women suffering foot pain showed higher pressure hypersensitivity in the plantar region than those FMS women without pain.

Self-efficacy and affect as mediators between pain dimensions and emotional symptoms and functional limitation in women with fibromyalgia.

The aim of this study was to investigate the role of self-efficacy and affect as mediators of the relationship between pain and several fibromyalgia (FM) symptoms (functional limitation, depression, and anxiety). We evaluated 144 women with FM for self-reported pain (numerical pain scale), pressure pain sensitivity (pressure pain thresholds), functional limitation (Fibromyalgia Impact Questionnaire), self-efficacy (Chronic Pain Self-Efficacy Scale), depression-anxiety (Hospital Anxiety and Depression Scale), and positive-negative affect (Positive-Negative Affect Scale). Mediating analyses were conducted with ordinary least squares multiple regression analysis. The results demonstrated that self-reported pain and pressure pain sensitivity exhibited significant relationships with functional limitation, anxiety, depression, self-efficacy, and affect. Affect mediated the relationship between pressure pain sensitivity and anxiety, whereas self-efficacy was the mediating variable between self-reported pain and functional limitation and depression. Our results support a complex nature of pain in women presenting with FM, as cognitive and emotional variables have different mediator relationships between pain dimensions and functional and emotional outcomes in women with FM.

Has catechol-O-methyltransferase genotype (Val158Met) an influence on endocrine, sympathetic nervous and humoral immune systems in women with fibromyalgia syndrome?

OBJECTIVE: Stress can play an important role in etiology of fibromyalgia syndrome (FMS) by activating the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS), and altering the immune system. The current study examined the influence of catechol-O-methyltransferase (COMT) Val158Met genotypes on salivary markers of HPA axis (cortisol), SNS (α-amylase), and immune (IgA) systems in women with FMS. METHODS: Seventy-six women with FMS diagnosed according to the American College of Rheumatology criteria participated in the study. Salivary cortisol, α-amylase activity, salivary flow rate, and IgA concentration were collected from nonstimulated saliva. A numerical pain rate scale (0 to 10) was used to assess the intensity of pain, whereas functional ability was determined using the Fibromyalgia Impact Questionnaire (FIQ). After amplifying Val158Met polymorphisms by polymerase chain reaction, 3 COMT genotypes were considered: Val/Val, Val/Met, and Met/Met. RESULTS: Women with FMS with the Met/Met genotype reported higher α-amylase activity, lower salivary flow rate, and lower IgA concentration than those women with FMS carrying the Val/Met (P<0.05) or Val/Val (P<0.01) genotypes. No difference in cortisol concentration (P>0.70) was found. These results were not associated with the intensity of pain, disability, and medication intake. CONCLUSIONS: The results suggest that women with FMS with the Met/Met genotype exhibit greater disturbed activity of the SNS and humoral immune system. These results provide initial evidence of a link between Val158Met polymorphism and dysfunctions in the SNS and humoral immune system in women with FMS.

Anxiety, depression and alexithymia in fibromyalgia: are there any differences according to age?

This article analyzes the evolution of alexithymia, anxiety, and depression associated with fibromyalgia (FM) in three age groups in comparison to how they evolve in the same age groups in healthy women. A total of 240 women participated in the study (120 diagnosed with fibromyalgia and 120 healthy women), divided into three age groups (≤35 years,>35 and <65 years, and ≥65 years old). Our analysis revealed that alexithymia, anxiety, and depression in FM patients showed increased levels compared to healthy controls. Also, young women with FM (under 35) show lower alexithymia, anxiety, and depression levels in comparison to older patients (≥65). Alexithymia in FM patients follows a similar pattern as in healthy women (although with significantly higher scores), increasing with age. Our results show that depression, anxiety, and alexithymia develop over age in a different way in FM patients than in healthy individuals, increasing over age.

Bilateral deficits in fine motor control ability and manual dexterity in women with fibromyalgia syndrome.

The aim of the current study was to investigate fine motor control ability and manual dexterity women with fibromyalgia syndrome (FMS) without symptoms in the upper extremity compared to healthy women. Subtests of the Purdue Pegboard Test (one-hand, bilateral and assembly) and of the Jebsen-Taylor hand-function test (writing, turning cards, picking up small, light and large heavy objects, simulated feeding and stacking checkers) were evaluated bilaterally in 20 women with FMS (aged 35-55 years) without symptoms in the upper limb and 20 age- and hand dominance-matched healthy women. Differences between sides and groups were analysed with several analysis of variance (ANOVA). The ANOVA revealed significant differences between groups (P < 0.001) and sides (P = 0.007) for one-hand pin placement subtest: women with FMS showed bilateral worse scores than controls. Patients also exhibited significantly lower scores in bilateral pin placement and assembly subtests when compared to healthy controls (P < 0.001). The ANOVA also revealed significant differences between groups for writing, turning over cards, picking up small objects, stacking checkers, picking up large light objects and picking up large heavy objects (all, P < 0.001): women with FMS needed more time for these subtests than healthy women with both hands. No difference for simulated feeding was found between groups. Our findings revealed bilateral deficits in fine motor control ability and manual dexterity in patients with FMS without symptoms in the upper extremity. These deficits are not related to the clinical features of the symptoms supporting an underlying central mechanism of altered motor control.

Catechol-O-methyltransferase Val158Met polymorphism influences anxiety, depression, and disability, but not pressure pain sensitivity, in women with fibromyalgia syndrome.

UNLABELLED: Our aim was to assess the relationship of the Val158Met polymorphism to pain, anxiety, depression, functional ability, and pressure pain sensitivity in women with fibromyalgia (FMS). One hundred (n = 100) women with FMS diagnosed according to the American College of Rheumatology criteria participated. A numerical pain rate scale (0-10) was used to assess the intensity of pain; the Hospital Anxiety and Depression Scale was calculated to determine anxiety and depression; and functional ability was determined with the Fibromyalgia Impact Questionnaire. Further, pressure pain thresholds (PPTs) were bilaterally assessed over C5-C6 zygapophyseal joints, second metacarpal, and tibialis anterior muscles. Finally, after amplifying Val158Met polymorphisms by polymerase chain reaction, catechol-O-methyltransferase (COMT) genotype was divided into Val/Val, Val/Met, or Met/Met genotypes. Women with FMS with the Met/Met genotype exhibited higher disability (F = 11.836; P < .001), anxiety (F = 13.385; P < .001), and depression (F = 6.931; P = .002) than those with Val/Val and Val/Met genotypes. No differences for the intensity of widespread pain (F = .154; P = .857) and PPT levels over C5-C6 joints (F = 1.014; P = .336), second metacarpal (F = .216; P = .806), and tibialis anterior muscle (F = 1.179; P = .311) were found. Our results suggest that the Val158Met COMT polymorphism modulated some psychological variables but not pressure pain sensitivity in FMS, because women carrying the Met/Met genotype show higher disability, depression, and anxiety but similar PPTs than those with Val/Met or Val/Val genotypes. This study is important because it strives to understand potential genetic factors that predispose some women with FMS to exhibit a more severe phenotypic expression of the disease. Future studies are needed to elucidate potential relevance of the differences. PERSPECTIVE: This study suggests that the Val158Met COMT polymorphism modulated some psychological variables but not pressure pain sensitivity in FMS because women with FMS carrying the Met/Met genotype exhibit higher disability, depression, and anxiety than but similar PPTs to those with Val/Met and Val/Val genotypes. This study provides further evidence of potential genetic factors that predispose women with FMS to exhibit the disease more severely.