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Item (506) The complex relationship between pain intensity and physical functioning in fibromyalgia: the mediating role of depression(The Journal of Pain, 2016) Steiner, Jennifer L.; Bigatti, Silvia M.; Slaven, James E.; Ang, Dennis C.Fibromyalgia (FM) is typically associated with the experience of diffuse pain and physical impairment. Depression also commonly co-exists in patients with FM, and it has been correlated with pain intensity and physical functioning. Previous research suggests an association between pain intensity and physical functioning; however, the direct causal relationship between improvements in pain intensity and in functioning is not observed in many FM patients. This may suggest that another factor such as depression is mediating this relationship. The present work examined the possibility of a mediating role of depression in the relationship between pain intensity and functioning over the course of time. 216 patients with FM completed self-report measures of pain intensity, depression, and physical impairment as part of a larger longitudinal study which investigated interventions to increase physical activity among FM patients. Assessments were completed at baseline, 12 weeks, 24 weeks, and 36 weeks. Longitudinal mediational analyses indicated that depression is a statistically significant partial mediator of the relationship between pain intensity and self-reported physical functioning at all four assessment points. To the authors’ knowledge, this is the first study to explicitly examine this relationship in a sample of FM patients, as well as the first to do so using a longitudinal design; this may significantly add to our understanding of the complexities behind creating improvements in physical functioning in this population. Clinical implication for these findings include focusing on depression and psychological correlates of depression as first line therapeutic targets in improving physical functioning of patients with FM, and treating co-morbid depression in patients with fibromyalgia earlier in the course of treatment to prevent engagement in and the perpetuation of the cycle of disability. This work was a secondary data analysis from a study funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.Item Analysis of Galvanic Skin Response: Potential Relationships to Stimulus Responsivity and Brain Dopamine Signal(2014-04-11) Chumin, Evgeny; Albrecht, Daniel; Yoder, KarenFibromyalgia is a chronic pain disorder that presents itself with no apparent medical explanation for the pain. Functional alterations of neurotransmitters such as dopamine (DA) have been implicated in fibromyalgia neuropathology. It is not known how central dopamine function in pain is associated with objective peripheral measurements that are thought to be associated with the presence of pain and stress. Galvanic skin response (GSR), is a physiological measure of nervous system activation. GSR could potentially give insight to novel aspects of DA function. In this study, GSR was recorded from fibromyalgia patients (FM) and healthy controls (HC) while they underwent scanning with [18F]-fallypride (FAL) Positron Emission Tomography (PET). FAL is a D2/D3 DA receptor antagonist that is sensitive to changes in DA levels in the brain. Given the involvement of DA in cognitive processes, FAL PET can be used to examine baseline DA activity as well as changes from baseline during cognitive load tasks. Relationships between GSR and working memory load, acute pain, and DA function were studied and compared between FM and HC.Item Assessing the Efficacy of Acceptance and Commitment Therapy in Reducing Schema-enmeshment in Fibromyalgia Syndrome(2014-09-04) Steiner, Jennifer Leah; Hirsh, Adam; Bigatti, Silvia M.; Ashburn-Nardo, Leslie; Stewart, Jesse C.; Grahame, Nicholas J.The presence of a chronic pain condition can have a profound impact on one’s self-concept. Some individuals may have had to make major lifestyle changes. As a result, some people may start to define themselves in terms of their pain, such that their self-schema and pain-schemas become intertwined in a process termed schema-enmeshment. It is thought that schema-enmeshment is related to psychological distress making it a prime target for intervention. Little research has been conducted on interventions to reduce schema-enmeshment. Acceptance-based interventions may be especially appropriate in reducing schema-enmeshment or the connection between self and illness symptoms as these interventions tend to emphasize learning to live with pain and other symptoms and to work toward important life goals rather than continually fighting against the condition and allowing it to control their life. This study is a randomized trial comparing Acceptance and Commitment Therapy (ACT) to education about pain management in a sample of women with Fibromyalgia Syndrome (FMS). The primary aim of this study was to assess the efficacy of ACT in reducing schema-enmeshment between self and pain, as well as enmeshment between self and other symptoms and FMS as a whole. In addition, this study also explored the role of pain acceptance, specifically activity engagement as a mediator of the relationship between treatment group membership and changes in schema-enmeshment. The data was analyzed as an intent-to-treat analysis using the “last measure carried forward” method. Results indicated that the ACT group reported statistically significant differences in self schema-enmeshment with FMS, fatigue, and cognitive symptoms, but not with pain, following the intervention, compared to the educational control group. In each of these cases, the ACT group experienced greater reductions in schema-enmeshment compared to the education group. Interestingly, no statistically significant differences were observed for schema-enmeshment with pain. Statistically significant group differences were also observed for acceptance of pain following the intervention. Finally, a mediational model in which changes in activity engagement (a form of pain acceptance) served as the mediator of the relationship between treatment group and changes in schema-enmeshment with FMS was tested. The model was tested using a bootstrapping method, and results revealed a trend toward a significant indirect effect of changes in activity engagement leading to changes in schema-enmeshment with FMS. Taken together, the results of this study indicate that ACT may be a promising intervention for targeting maladaptive beliefs about the self in relation to illness, especially schema-enmeshment of self with illness and illness symptoms. Additionally, there is evidence that ACT may target key constructs such as activity engagement, which may be related to other cognitive and behavioral changes. Future directions for research and clinical practice related to ACT as an intervention for FMS are discussed in depth.Item Clinical Characterization of Juvenile Fibromyalgia in a Multicenter Cohort of Adolescents Enrolled in a Randomized Clinical Trial(Wiley, 2023) Lynch-Jordan, Anne M.; Connelly, Mark; Guite, Jessica W.; King, Christopher; Goldstein-Leever, Alana; Logan, Deirdre E.; Nelson, Sarah; Stinson, Jennifer N.; Ting, Tracy V.; Wakefield, Emily O.; Williams, Amy E.; Williams, Sara E.; Kashikar-Zuck, Susmita; Fibromyalgia Integrative Training for Teens Clinical Trial Study Group; Childhood Arthritis and Rheumatology Research Alliance Pain Workgroup Investigators; Psychiatry, School of MedicineObjective: Juvenile fibromyalgia (JFM) is a complex chronic pain condition that remains poorly understood. The study aimed to expand the clinical characterization of JFM in a large representative sample of adolescents with JFM and identify psychological factors that predict pain interference. Methods: Participants were 203 adolescents (ages 12-17 years) who completed baseline assessments for the multisite Fibromyalgia Integrative Training for Teens (FIT Teens) randomized control trial. Participants completed the Pain and Symptom Assessment Tool, which includes a Widespread Pain Index (WPI; 0-18 pain locations) and Symptom Severity checklist of associated somatic symptoms (SS; 0-12) based on the 2010 American College of Rheumatology criteria for fibromyalgia. Participants also completed self-report measures of pain intensity, functional impairment, and psychological functioning. Results: Participants endorsed a median of 11 painful body sites (WPI score) and had a median SS score of 9. Fatigue and nonrestorative sleep were prominent features and rated as moderate to severe by 85% of participants. Additionally, neurologic, autonomic, gastroenterologic, and psychological symptoms were frequently endorsed. The WPI score was significantly correlated with pain intensity and catastrophizing, while SS scores were associated with pain intensity and all domains of physical and psychological functioning. Depressive symptoms, fatigue, and pain catastrophizing predicted severity of pain impairment. Conclusion: JFM is characterized by chronic widespread pain with fatigue, nonrestorative sleep, and other somatic symptoms. However, how diffusely pain is distributed appears less important to clinical outcomes and impairment than other somatic and psychological factors, highlighting the need for a broader approach to the assessment and treatment of JFM.Item The Complex Relationship between Pain Intensity and Physical Functioning in Fibromyalgia: The Mediating Role of Depression(Journal of Applied Biobehavioral Research, 2017) Steiner, Jennifer L.; Bigatti, Silvia M.; Slaven, James E.; Ang, Dennis C.Fibromyalgia (FM) is typically associated with the experience of diffuse pain and physical impairment.Depression also commonly co-exists in patients with FM, and has been correlated with pain intensity and physical functioning.Previous research suggests an association between pain intensity and physical functioning; however, the direct causal relationship between improvements in pain intensity and in functioning is not observed in many FM patients.This may suggest that another factor such as depression is mediating this relationship. The present work examinedmediating role of depression. METHODS: 216 patients with FM completed measures of pain intensity, depression, and physical functionas part of a larger longitudinal study.Assessments were completed at baseline, 12, 24, and 36 weeks.RESULTS: Longitudinal mediational analyses indicated that depression is a partial mediator of the relationship between pain intensity and physical functioningat all four assessment points.Beta coefficients for the path from pain to physical functioning ranged from 0.18 –0.36, with attenuated path coefficients ranging from 0.03 –0.08, still showing significant but decreased associations when depression was added as a mediator. CONCLUSIONS: Clinical implication includes the importance of treating co-morbid depression in patients with fibromyalgia early in the course of treatment to prevent engagement in the cycle of disability.Item Differential dopamine function in fibromyalgia(Springer, 2016-09) Albrecht, Daniel S.; MacKie, Palmer J.; Kareken, David A.; Hutchins, Gary D.; Chumin, Evgeny J.; Christian, Bradley T.; Yoder, Karmen K.; Radiology and Imaging Sciences, School of MedicineApproximately 30% of Americans suffer from chronic pain disorders, such as fibromyalgia (FM), which can cause debilitating pain. Many pain-killing drugs prescribed for chronic pain disorders are highly addictive, have limited clinical efficacy, and do not treat the cognitive symptoms reported by many patients. The neurobiological substrates of chronic pain are largely unknown, but evidence points to altered dopaminergic transmission in aberrant pain perception. We sought to characterize the dopamine (DA) system in individuals with FM. Positron emission tomography (PET) with [18F]fallypride (FAL) was used to assess changes in DA during a working memory challenge relative to a baseline task, and to test for associations between baseline D2/D3 availability and experimental pain measures. Twelve female subjects with FM and eleven female controls completed study procedures. Subjects received one FAL PET scan while performing a “2-back” task, and one while performing a “0-back” (attentional control, “baseline”) task. FM subjects had lower baseline FAL binding potential (BP) in several cortical regions relative to controls, including anterior cingulate cortex. In FM subjects, self-reported spontaneous pain negatively correlated with FAL BP in the left orbitofrontal cortex and parahippocampal gyrus. Baseline BP was significantly negatively correlated with experimental pain sensitivity and tolerance in both FM and CON subjects, although spatial patterns of these associations differed between groups. The data suggest that abnormal DA function may be associated with differential processing of pain perception in FM. Further studies are needed to explore the functional significance of DA in nociception and cognitive processing in chronic pain.Item THE IMPACT OF FIBROMYALGIA ON RESOURCE USE IN THE UK PRIMARY CARE SETTING(2008-10-10T18:19:38Z) Le, Trong Kim; Mac Kinnon, Joyce L.; Bayliss, Amy J.; Schellhase, EllenFibromyalgia (FMS) is a complex, chronic condition involving persistent and widespread pain of unknown origin. FMS is sometimes mistaken as psychiatric in origin; however, the precise origin and cause of FMS is unknown (Klippel et al., 1998). Worldwide prevalence rates range from 0.18-12%, with 0.18% in the United Kingdom (UK) (Hughes et al., 2006), 2% in the United States (US) (Wolfe et al., 1997), and 12% in Spain (Carmona et al., 2001). In the UK, there is debate over the existence of FMS (Bohr, 1995), and the reluctance of a general practitioner (GP) to diagnose conditions that are poorly defined (Hughes et al., 2006). Primary symptoms of FMS include generalized muscular pain, multiple tender points, sleep disruption and excessive fatigue. Additional symptoms include headaches, memory and concentration problems, dizziness, numbness/tingling, itching, fluid retention, abdominal cramps or pelvic pain and diarrhea (Hudson et al., 1992). Clearly, these symptoms may have an immense impact on daily life, limiting an individual’s functioning and emotional well-being. FMS is associated with significant societal and health care costs. Patients with FMS may repeatedly present to the general practitioner with various symptoms before a definitive diagnosis of FMS is made. As a result, general practitioners may be more likely to diagnose FMS in patients who frequently present with symptoms related to FMS, while patients who meet the diagnostic criteria but who rarely present at the practice may be missed (Ehrlich, 2003). The condition is of unknown etiology, and this, together with the lack of verifiable diagnostic criteria (i.e. lab tests), has led some to speculate that the disease does not or is at best a surrogate marker for underlying psychosocial problems. As such, the very process of diagnosing a patient with FMS may exacerbate symptoms and lead to increased dependence on health care providers (Ehrlich, 2003). This study examined the diagnoses of FMS made in “real-life” clinical practice and recorded by general practitioners in a large primary care population in the UK.Item Predictors of Physical Activity in Patients with Fibromyalgia: A Path Analysis(Wolters Kluwer, 2022) Kaleth, Anthony S.; Bigatti, Silvia M.; Slaven, James E.; Kelly, Nicholas; Ang, Dennis C.; Kinesiology, School of Health and Human SciencesBackground/objective: The aim of this study was to identify psychological factors that influence moderate-vigorous physical activity (MVPA) participation in patients with fibromyalgia. Methods: In this secondary data analysis, 170 patients received personalized exercise plans and completed baseline and follow-up assessments of self-reported physical activity at weeks 12, 24, and 36. Structural equation modeling was used to examine the predictive strengths of psychological factors (exercise self-efficacy, perceived barriers, and intention) on MVPA participation. Results: Using a threshold increase in MVPA of 10 or greater metabolic equivalent hours per week (MET h/wk), 3 groups were defined based on subjects who achieved a minimum increase of 10 MET h/wk that was sustained for at least 12 weeks (SUS-PA), achieved an increase of 10 MET h/wk that was not sustained for at least 12 weeks (UNSUS-PA), and did not achieve an increase of 10 MET h/wk (LO-PA). Increases in exercise self-efficacy and intention and reductions in perceived barriers were associated with increased volume of PA, showing the greatest change in the SUS-PA, followed by UNSUS-PA. For the LO-PA group, there was no change in exercise self-efficacy, a decrease in intention, and an increase in barriers. Using path analysis, exercise self-efficacy and perceived barriers were associated with higher volumes of physical activity via greater intention to engage in MVPA. Conclusions: For patients with fibromyalgia, exercise self-efficacy, perceived barriers, and intention to exercise are important constructs for increasing physical activity. Our findings provide guidance for practitioners who seek to promote physical activity in fibromyalgia and suggestions for researchers aiming to improve prediction models.Item QS9: Host Biofilm Interaction In Breast Implant Illness(Wolters Kluwer, 2021-07) Khan, Imran; Minto, Robert E.; Kelley-Patteson, Christine; Van Natta, Bruce; Mohan, Ganesh; Suh, Lily; Singh, Kanhaiya; Lester, Mary; VonDerHaar, R. Jason; Gordillo, Gayle M.; Hassanein, Aladdin; Sen, Chandan K.; Kadin, Marshall E.; Sinha, Mithun; Surgery, School of MedicinePurpose: Breast Implant Illness (BII) is patient-described constellation of symptoms that are believed to be related to their breast implant. The symptoms described include fibromyalgia, chronic fatigue and a host of other symptoms that are often associated with autoimmune illnesses. In this work, we report that bacterial biofilm associated with breast implant, metabolize fatty acid oleic acid present in the breast tissue milieu to oxylipins, one such oxylipin identified from this study is (10S)-hydroxy-(8E)-octadecenoic acid (10-HOME). We hypothesize that immunomodulatory effects of oxylipin 10-HOME produced by biofilm present on the implant could be correlated with BII pathogenesis. Methods: Capsulectomy and breast implants from clinically indicated procedures for patients requesting prosthetic removal were collected using clinical parameters outlined in previous studies, and questionnaire screened for the commonly reported symptoms associated with BII. Predictive variables included age, diabetes status, co-morbidities, nature and duration of implant. Scanning electron microscopy (SEM), Wheat Germ Agglutinin (WGA) and 16SrRNA sequencing were used for bacterial biofilm bacterial identification. 10-HOME was quantitated through targeted and untargeted lipidomic analyses using LC-MS-MS. Results: Sixty eight Implant, associated capsules and breast tissue specimen were collected for BII (n=46) and two control groups, group I, (non-BII, n=14) patients with breast implants, no BII symptoms. Group II (normal tissue, n = 8), patients without an implant, whose breast tissue was removed due to surgical procedures. Bacterial biofilm was detected through SEM in both BII and non BII cohorts. However, WGA analysis (quantitative analysis) indicated increased abundance of biofilm in the BII cohort (n=7, p=0.0036). 16SrRNA (genomic) sequencing identified increased abundance of Staphylococcus epidermidis (Fisher’s exact test, p<0.001) in the BII group (63.04%) compared to non-BII group (14.3%) and the normal group. The BII group was 9.8 times significantly more likely to have Staphylococcus epidermidis colonization compared to the non-BII group (p=0.003, logistic regression), compared to normal, it is 17.4 times significantly more likely to have Staphylococcus epidermidis (p=0.0021). Elevated levels of 10-HOME BII compared to non-BII samples, (p < 0.0001) were observed through mass spectrometry. Positive correlation was observed between bacterial abundance and concentration of 10-HOME in BII subjects (R2=0.88). Similar correlation was observed in BII subjects with Staphylococcus epidermidis (R2=0.77). Conclusion: This study investigated the biofilm hypothesis of breast implant illness through a host-pathogen interaction. The breast microenvironment led to formation of biofilm derived 10-HOME from host oleic acid. The study provides the first evidence of a possible correlation between bacterial biofilm and biofilm derived 10-HOME in the context of 10-HOME. In consideration of reports of biofilm association with other metal implants, the findings of this study can possibly explain autoimmune response associated with those implants.Item A qualitative study of risk and resilience in young adult women with a history of juvenile-onset fibromyalgia(BMC, 2021-08-17) Daffin, Morgan; Lynch-Milder, Mary K.; Gibler, Robert C.; Murray, Caitlin; Green, Carly M.; Kashikar-Zuck, Susmita; Psychiatry, School of MedicineBackground: Juvenile-onset Fibromyalgia (JFM) is a chronic pain condition characterized by widespread musculoskeletal pain, fatigue, sleep difficulties, mood concerns, and other associated symptoms. Although diagnosed in childhood, JFM often persists into adulthood can result in continued physical, social, and psychological impairment. The purpose of this qualitative study was to identify themes of risk and resilience for long-term outcomes among young adults diagnosed with JFM in childhood. Methods: The sample included 13 young adults (ages 26-34) who had been diagnosed with JFM in adolescence. Focus groups were used to elicit qualitative information about living with JFM and perceived challenges and buffering factors impacting their adjustment. Results: The majority of participants (80%, N = 12) continued to meet criteria for fibromyalgia (FM). An iterative, thematic analysis revealed themes of resilience (e.g., greater acceptance, re-setting expectations, active coping, addressing mental health) and risk (e.g., lack of information, stigma, isolation, negative healthcare experiences). Conclusion: Results suggest the need for longer follow-up of youth with JFM as they transition to adulthood with multidisciplinary care and more attention to education about JFM and associated symptoms such as fatigue, as well as ongoing support for coping and mental health needs. A holistic approach to care during the transition years could be beneficial to minimize impact of JFM on long-term functioning.