Long versus short-term opioid therapy for fibromyalgia syndrome and risk of depression, sleep disorders and suicidal ideation: a population-based, propensity-weighted cohort study.

OBJECTIVE: Fibromyalgia syndrome (FMS) is characterised by widespread pain and is associated with mood disorders such as depression as well as poor sleep quality. These in turn have been linked to increased risk of suicidal ideation. Clinical guidelines generally do not recommended opioids in FMS, but they are routinely prescribed to a considerable proportion of FMS patients. We assessed the association of long-term opioid prescription for FMS with risk of depression, sleep disorders and suicidal ideation, when compared with short-term opioid use. METHODS: Retrospective cohort study combing several population-wide databases covering a population of five million inhabitants, including all adults who received an initial opioid prescription from 2014 to 2018 specifically prescribed for FMS. We examined the occurrence of depression, sleep disorders or suicidal ideation outcomes in patients with an initial long-term opioid prescription (>90 days) versus those who received a short-term treatment (<29 days). We employed multivariable Cox regression modelling and inverse probability of treatment weighting based on propensity scores and we performed several sensitivity analyses. RESULTS: 10 334 patients initiated short-term (8309, 80.40%) or long-term (2025, 19.60%) opioids for FMS. In main adjusted analyses, long-term opioid use was associated with an increased risk for depression (HR: 1.58, 95% CI 1.29 to 1.95) and sleep disorder (HR: 1.30, 95% CI 1.09 to 1.55) but not with suicidal ideation (HR: 1.59, 95% CI 0.96 to 2.62). In models assessing outcomes since day 90, an increased risk for suicidal ideation was observed (HR: 1.76, 95% CI 1.05 to 2.98). CONCLUSION: These findings suggest that continued opioid use for 90 days or more may aggravate depression and sleep problems in patients with FMS when compared with patterns of short-term treatment.

Psychological Pain, Hopelessness and Suicide Ideation in Female Patients with Fibromyalgia.

Objective: Objective: The aim of this study was to investigate if psychache and hopelessness may serve as reliable predictors of suicidal ideation among female fibromyalgia (FM) patients. Method: This was a cross-sectional study of 50 women with FM, examining the relationship between psychological pain, hopelessness, depressive symptoms, and suicidal ideation. FM diagnosis was confirmed by the American College of Rheumatology (ACR) criteria. Demographic data, the Mini International Neuropsychiatric Interview (MINI 7.0.2), the Beck Depression Inventory-II (BDI-II), the Beck Hopelessness Scale (BHS), the Pittsburgh Sleep Quality Index (PSQI) and the Psychache Scale were utilized to assess these relationships and their predictive value for suicidality. Results: The mean age of the participants was 50.2 years (±8.7). Thirty-two (64%) patients had current major depression, 11 (22%) had bipolar disorder, 20 (40%) presented passive suicidal ideation and 14 (28%) presented active suicidal ideation. Psychological pain correlated with both depressive symptoms (p<0.01; r= 0.648) and hopelessness (p=0.029; r=0.312) but did not predict suicidal ideation. Logistic regression analyses revealed depressive symptom severity as a predictor of passive suicidal ideation (odds ratio = 1.486; 95% CI: 1.017 - 2.170), while hopelessness predicted active suicidal ideation (odd ratio = 1.356; 95% CI, 1.049 - 1.753). Conclusions: FM female patients showed increased prevalence of suicidal ideation. Hopelessness predicts active suicidal ideation but psychological pain did not serve as predictive factor for suicide ideation among female FM patients.

Unraveling Shared Diagnostic Biomarkers of Fibromyalgia in Ankylosing Spondylitis: Evidence from Comprehensive Bioinformatic Analysis and Experimental Validation.

Background: Fibromyalgia (FM) is a commonly encountered disease featuring chronic generalized pain, sleep disorder, and physical fatigue. Ankylosing spondylitis (AS) causes chronic lumbodorsalgia involving the sacroiliac joint, often clinically complicated with FM. Nevertheless, the pathophysiology of FM secondary to AS is still lacking. Methods: Gene expression data of the whole blood in FM and AS patients were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were evaluated employing the "limma" package. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented to explore common pathways. Weighted gene correlation network analysis (WGCNA) was adopted to screen key gene modules. Three machine learning algorithms were performed to refine the intersected genes. Single sample gene set enrichment analysis (ssGSEA) was applied to explore the relationships between hub genes and immune cells. The dependability of hub gene expressions in clinical blood specimens was verified by RT-PCR. Molecular docking was conducted to predict small molecular compounds targeting hub genes. Results: DEG analysis screened 419 shared up-regulated and 179 shared down-regulated genes in FM and AS. A total of 143 common genes in positive modules of AS and FM were identified via WGCNA. Six key genes (CETN3, CACNA1E, OGT, QRFPR, SCOC, DIAPH1) were obtained by intersecting the WGCNA-derived shared genes and up-regulated DEGs. CETN3 and CACNA1E were refined as hub genes via three machine-learning algorithms and they showed excellent diagnostic value for FM and AS. However, ssGSEA exhibited different immune cell infiltration patterns in FM and AS. Gabapentin enacarbil was recognized as a potential therapeutic drug for AS-FM patients. Conclusion: This study reveals the shared hub genes in AS and FM. Meanwhile, these results were confirmed in clinical samples. CETN3 and CACNA1E may become potential diagnostic biomarkers and therapeutic targets for patients with AS complicated by FM.

Electroacupuncture Reduced Fibromyalgia-Pain-like Behavior through Inactivating Transient Receptor Potential V1 and Interleukin-17 in Intermittent Cold Stress Mice Model.

Fibromyalgia (FM) is a widespread musculoskeletal pain associated with psychological disturbances, the etiopathogenesis of which is still not clear. One hypothesis implicates inflammatory cytokines in increasing central and peripheral sensitization along with neuroinflammation, leading to an elevation in pro-inflammatory cytokines, e.g., interleukin-17A (IL-17A), enhanced in FM patients and animal models. The intermittent cold stress (ICS)-induced FM-like model in C57BL/6 mice has been developed since 2008 and proved to have features which mimic the clinical pattern in FM patients such as mechanical allodynia, hyperalgesia, and female predominance of pain. Electroacupuncture (EA) is an effective treatment for relieving pain in FM patients, but its mechanism is not totally clear. It was reported as attenuating pain-like behaviors in the ICS mice model through the transient receptor potential vanilloid 1 (TRPV1) pathway. Limited information indicates that TRPV1-positive neurons trigger IL-17A-mediated inflammation. Therefore, we hypothesized that the IL-17A would be inactivated by EA and TRPV1 deletion in the ICS-induced FM-like model in mice. We distributed mice into a control (CON) group, ICS-induced FM model (FM) group, FM model with EA treatment (EA) group, FM model with sham EA treatment (Sham) group, and TRPV1 gene deletion (Trpv1-/-) group. In the result, ICS-induced mechanical and thermal hyperalgesia increased pro-inflammatory cytokines including IL-6, IL-17, TNFα, and IFNγ in the plasma, as well as TRPV1, IL-17RA, pPI3K, pAkt, pERK, pp38, pJNK, and NF-κB in the somatosensory cortex (SSC) and cerebellum (CB) lobes V, VI, and VII. Moreover, EA and Trpv1-/- but not sham EA countered these effects significantly. The molecular mechanism may involve the pro-inflammatory cytokines, including IL-6, IL-17, TNFα, and IFNγ. IL-17A-IL-17RA play a crucial role in peripheral and central sensitization as well as neuroinflammation and cannot be activated without TRPV1 in the ICS mice model. EA alleviated FM-pain-like behaviors, possibly by abolishing the TRPV1- and IL-17A-related pathways. It suggests that EA is an effective and potential therapeutic strategy in FM.

Effectiveness of Transcranial Direct Current Stimulation (tDCS) during a Virtual Reality Task in Women with Fibromyalgia-A Randomized Clinical Study.

BACKGROUND/OBJECTIVES: Fibromyalgia (FM) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and impaired motor performance. This study aimed to investigate the effects of transcranial direct current stimulation (tDCS) during virtual reality (VR) tasks on the motor performance of women with FM. METHODS: Participants were divided into two groups: Group A received active tDCS for 10 days followed by sham tDCS for 10 days, while Group B received the opposite sequence. Both groups performed VR tasks using MoveHero software (v. 2.4) during the tDCS sessions. Motor performance was assessed by the number of hits (movement with correct timing to reach the targets) and absolute (accuracy measure) and variable (precision measure) errors during VR tasks. Participants were 21 women, aged 30-50 years, and diagnosed with FM. RESULTS: Group A, which received active tDCS first, presented significant improvements in motor performance (number of hits and absolute and variable errors). The benefits of active tDCS persisted into the sham phase, suggesting a lasting neuroplastic effect. CONCLUSIONS: tDCS during VR tasks significantly improved motor performance in women with FM, particularly in complex, extensive movements. These findings indicate that tDCS enhances neuroplasticity, leading to sustained motor improvements, making it a promising therapeutic tool in FM rehabilitation.

The Link between Endogenous Pain Modulation Changes and Clinical Improvement in Fibromyalgia Syndrome: A Meta-Regression Analysis.

Conditioned pain modulation (CPM) and temporal summation (TS) tests can measure the ability to inhibit pain in fibromyalgia syndrome (FMS) patients and its level of pain sensitization, respectively. However, their clinical validity is still unclear. We studied the association between changes in the CPM and TS tests and the clinical improvement of FMS patients who received therapeutic intervention. We systematically searched for FMS randomized clinical trials with data on therapeutic interventions comparing clinical improvement (pain intensity and symptom severity reduction), CPM, and TS changes relative to control interventions. To study the relationship between TS/CPM and clinical measures, we performed a meta-regression analysis to calculate odds ratios. We included nine studies (484 participants). We found no significant changes in TS or CPM by studying all the interventions together. Our findings show that this lack of difference is likely because pharmacological and non-pharmacological interventions resulted in contrary effects. Non-pharmacological interventions, such as non-invasive neuromodulation, showed the largest effects normalizing CPM/TS. Meta-regression was significantly associated with pain reduction and symptom severity improvement with normalization of TS and CPM. We demonstrate an association between clinical improvement and TS/CPM normalization in FMS patients. Thus, the TS and CPM tests could be surrogate biomarkers in FMS management. Recovering defective endogenous pain modulation mechanisms by targeted non-pharmacological interventions may help establish long-term clinical recovery in FMS patients.

The Hedonic Experience Associated with a Gentle Touch Is Preserved in Women with Fibromyalgia.

Background/Objectives: Although manual therapies can be used for pain alleviation in fibromyalgia, there is no clear evidence about the processing of gentle, affective touch in this clinical condition. In fact, persistent painful sensations and psychological factors may impact the hedonic experience of touch. Methods: This observational cross-sectional study compared the subjective experience of affective touch between 14 women with fibromyalgia (age range: 35-70; range of years of education: 5-13) and 14 pain-free women (age range: 18-30; range of years of education: 13-19). The participants rated the pleasantness of slow and fast touches delivered by a brush, the experimenter's hand, and a plastic stick. Tactile stimuli were either imagined or real to disentangle the contribution of top-down and bottom-up sensory components. Additionally, a self-report questionnaire explored the lifetime experiences of affective touch. Results: Akin to healthy counterparts, individuals with fibromyalgia rated slow touches delivered by the experimenter's hand or a brush as more pleasant than fast touches, regardless of whether they were imagined or real. However, the intensity of pain affects only the imagined pleasantness in our participants with fibromyalgia. Furthermore, despite the fibromyalgia patients reporting fewer experiences of affective touch in childhood and adolescence, this evidence was not associated with the experimental outcomes. Conclusions: The hedonic experience of affective touch seems preserved in fibromyalgia despite poor intimate bodily contact in youth. We confirmed that bottom-up and top-down factors contribute to the affective touch perception in fibromyalgia: bodily pain may impact even more the expected pleasure than the actual experience. Future investigations may introduce neurophysiological measures of the implicit autonomic responses to affective touch in fibromyalgia. To conclude, although preliminary, our evidence may be in favor of manual therapies for pain relief in fibromyalgia.

Does practice make perfect? Functional connectivity of the salience network and somatosensory network predicts response to mind-body treatments for fibromyalgia.

Background: Mind-body treatments can improve coping mechanisms to deal with pain, improve the quality of life of patients with fibromyalgia syndrome (FMS), and reduce perceived pain in some cases. However, responses to these treatments are highly variable, the mechanisms underpinning them remain unclear, and reliable predictors of treatment response are lacking. We employed resting-state blood oxygen level-dependent (rsBOLD) functional magnetic resonance imaging (fMRI) to examine changes in brain functional connectivity (FC) following mind-body treatment that may relate to and predict pain relief. Methods: We recruited patients with FMS who underwent either mindfulness-based stress reduction (MBSR; n = 18) or a psychoeducational program (FibroQoL; n = 22) and a treatment-as-usual FMS group (TAU; n = 18). We collected rsBOLD data, alongside subjective pain, anxiety, depression, and catastrophizing measures prior to and following treatments. We examined behavioral changes and FC changes in the salience network (SN) and sensorimotor network (SMN) and performed regression analyses to identify predictors for treatment response. Results: The MBSR and FibroQoL groups experienced significant reductions in pain catastrophizing. After treatment, the FC of the sensorimotor cortex with the rest of the SMN became significantly reduced in the MBSR group compared to the TAU group. The FC between the SN and the SMN at baseline was negatively correlated with pain reductions following MBSR but positively correlated with pain reductions in the FibroQoL group. These results yielded large to very large effect sizes. Following MBSR, only for those patients with lower baseline SMN-SN FC, minutes of mindfulness practice were positively associated with clinical improvement (small to medium effect size). Conclusions: Different mind-body treatments are underpinned by discrete brain networks. Measures of the functional interplay between SN and SMN have the potential as predictors of mind-body treatment response in patients with FMS.

Exploring the psychopathological profile of fibromyalgia: insights from the personality assessment inventory and its association with disease impact.

Background: Fibromyalgia (FM) is a complex rheumatic disorder characterized by chronic nociplastic pain and central sensitization. Psychopathological conditions can influence FM symptoms, which worsen their condition. However, not all patients with FM have psychopathological disorders, indicating a heterogeneous population. Objective: To investigate the psychopathological profile and personality disorders in patients with FM and its relationship impact on this disease. Methods: An observational and cross-sectional comparative study was conducted with a sample of 90 women, mean age 48.7 years (SD = 8.12), from Hospital del Mar, Barcelona. The Personality Assessment Inventory (PAI) and the Fibromyalgia Impact Questionnaire (FIQ) were used for assessment. Results: FM patients predominantly exhibited psychopathological profiles resembling affective disorders (37.7%) and Cluster C personality disorders (58.8%). The severity of FM's impact was related to affective disorder symptoms, hypervigilance, derealization, somatization, and Cluster B personality disorder (emotional instability). Different rheumatic symptoms correlated with specific psychopathological patterns. Increased somatic symptoms on the FIQ were related to an unstable and dependent personality, while heightened emotional symptoms on the FIQ were associated with avoidance, borderline traits, and passive-aggressive reactions. Conclusion: Recognizing psychopathological aspects is crucial for managing FM. The PAI is a valuable tool for establishing its psychopathological multidimensional profile, which predominantly shows an affective spectrum conditions and comorbid Cluster C personality disorder, exacerbating the disease's impact.

Psychometric properties of Polish version of the 36-item WHODAS 2.0 in individuals with fibromyalgia.

Fibromyalgia (FM) is chronic, widespread musculoskeletal pain and accompanying fatigue, sleep disturbances, cognitive, psychological, and somatic symptoms. The aim of the study is to assess the psychometric properties of the Polish version of the 36-item WHODAS 2.0 in FM patients. This is a cross-sectional study involving 456 FM polish patients. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) 36-item version, the Fibromyalgia Impact Questionnaire (FIQ) and Beck's Depression Inventory (BDI) were used as an assessment tool in the study. The internal consistency of the 36-item WHODAS 2.0 was assessed using Cronbach's alpha. Values ranging from 0.824 to 0.951 were obtained. The interclass correlation coefficients (ICC) were very high. Internal structure of the 36-item WHODAS 2.0 was checked with Confirmatory Factor Analysis (CFA). RMSEA = 0.069, CFI = 0.963, TLI = 0.96, SRMR = 0.081 proved exactness of original six-dimensional structure of WHODAS 2.0. External validity was assessed by correlating the 36-item WHODAS 2.0 scores with the scores of two previously validated tools: FIQ and BDI. Positive correlations were obtained between the 36-item WHODAS 2.0 and these tools. Based on the conducted research, it has been shown that the 36-item WHODAS 2.0 is a reliable and valid tool for assessing disability in individuals with FM in Poland.

Pain neuroscience education and motor imagery-based exercise protocol for patients with fibromyalgia: A randomized controlled trial.

BACKGROUND: This study is a randomized controlled, biopsychosocial study investigating the effectiveness of pain neuroscience education (PNE) and motor imagery-based exercise protocol (MIEP) on fibromyalgia pain. METHODS: Our study has four groups (MIEP n = 12, PNE n = 12, MIEP + PNE n = 14, Control n = 12) and all participants (n = 50) consist of patients diagnosed with fibromyalgia with chronic back pain. The primary outcome measure was pain intensity, and secondary outcome measures were beliefs, kinesiophobia, anxiety-depression, cognitive-mood, self-esteem, and body awareness. RESULTS: A statistically significant decrease in pain intensity was observed in all experimental groups, without any group being superior (Visual Analog Scale [VAS]: MIEP + PNE p = .003, 95% confidence interval [CI], -4.7078 to -0.9922; MIEP p = .003, 95% CI, -5.4806 to -1.0194; PNE p = .002, 95% CI, -3.6139 to -1.5461). There was a significant improvement in organic beliefs in both groups where PNE was applied (MIEP + PNE: p = .017, 95% CI, -7.8211 to -0.3189; PNE: p = .003, 95% CI, -9.7999 to -0.0401). A significant superiority in organic pain beliefs was detected in the MIEP + PNE group compared to the control group (p = .008, 95% CI, 1.7241-9.4959). CONCLUSIONS: According to this study, in which MIEP and PNE were combined, there was a decrease in pain intensity when both applications were applied together and when they were applied one by one. MIEP has improved her motor imagery ability, improved pain and increased body awareness. PNE has improved people's organic pain beliefs; removed people from fears, catastrophizing, and negative thoughts about pain; improved easier management of psychological processes and cognitive-emotion regulation ability.

Identifying microRNAs Possibly Implicated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Review.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are chronic syndromes of unknown etiology, accompanied by numerous symptoms affecting neurological and physical conditions. Despite frequent revisions of the diagnostic criteria, clinical practice guidelines are often outdated, leading to underdiagnosis and ineffective treatment. Our aim was to identify microRNA (miRNA) biomarkers implicated in pathological mechanisms underlying these diseases. A comprehensive literature review using publicly accessible databases was conducted. Interesting miRNAs were extracted from relevant publications on ME/CFS and/or FM, and were then linked to pathophysiological processes possibly manifesting these chronic diseases. Dysregulated miRNAs in ME/CFS and FM may serve as promising biomarkers for these diseases. Key identified miRNAs, such as miR-29c, miR-99b, miR-128, miR-374b, and miR-766, were frequently mentioned for their roles in immune response, mitochondrial dysfunction, oxidative stress, and central sensitization, while miR-23a, miR-103, miR-152, and miR-320 were implicated in multiple crucial pathological processes for FM and/or ME/CFS. In summary, both ME/CFS and FM seem to share many dysregulated biological or molecular processes, which may contribute to their commonly shared symptoms. This miRNA-based approach offers new angles for discovering molecular markers urgently needed for early diagnosis or therapeutics to tackle the pathology of these medically unexplained chronic diseases.

Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms. METHODS: A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software. RESULTS: This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31-.67]; Z = 5.29, p < .01) and ß1 adrenergic receptor expression (SMD = .79 [.06-1.52]; Z = 2.13; p = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18-.97]; Z = 2.85, p < .01), ß2 AR (SMD = .41 [.02-.81]; Z = 2.04; p = .04) and COMT (SMD = .42 [.03-.81]; Z = 2.11; p = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [-.47 to -.70]; Z = 2.10; p = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = -.79 [-1.27 to -.30]; Z = -3.14; p < .01). CONCLUSION: This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM.

The effect of fibromyalgia syndrome on female patients diagnosed with chronic migraine.

OBJECTIVE: To compare pain, quality of life, sleep, anxiety and depression, central sensitization, and functionality between chronic migraine (CM) patients with comorbid fibromyalgia syndrome (FMS) and patients with CM alone. METHOD: Thirty three female patients with CM and thirty three female patients with CM+FMS were enrolled in the study. Demographic and clinical characteristics of the patients were recorded. FM was diagnosed based on the 2016 American College of Rheumatology diagnostic criteria. All participants were evaluated with Allodynia Symptom Checklist, Short Form-36 (SF-36), Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT-6) questionnaires, and Central Sensitization Inventory (CSI). FM patients were also evaluated with Fibromyalgia Impact Questionnaire (FIQ). RESULTS: The average number of headache days was significantly higher in patients with CM+FMS (p = 0.006). Among migraine accompanying symptoms, the number of patients with phonophobia was significantly higher in patients with CM+FMS (p = 0.008). While CSI score was 39.0 ±â€¯11.7 in CM patients, it was 52.2 ±â€¯9.2 in CM+FMS patients. CSI scores were higher in CM+FMS patients (p < 0.001). SF-36 sub-cores, including physical function, energy/fatigue, emotional well-being, and general health scores, were lower in CM+FMS patients (p < 0.05). Sleep duration was significantly lower and use of medication to sleep was more common in same group (p < 0.05). FIQ score in CM+FMS patients was associated with quality of life scores, sleep quality, anxiety, and central sensitization scores (p < 0.05). CONCLUSION: In patients with chronic migraine, FMS comorbidity negatively affects the quality of life and significantly increases central sensitization.

Nano-pregabalin effectively mitigates Glut, CGRP and NE neurotransmitters abnormalities in the brain of gamma irradiated rats with reserpine-induced fibromyalgia model: Behavioral and neurochemical studies.

AIMS: Fibromyalgia (FM) is an idiopathic syndrome with painful burdensome symptoms. Radiotherapy is one of the main therapeutic modalities for treating various malignancies and there is a probable association between FM exacerbation and exposure to ionizing radiation. Based on that nanomedicines progressively being explored for their promising applications in medicine, the aim of the current study is to assess the possible therapeutic benefits of nanoform of pregabalin (N-PG) in managing FM symptoms during being exposed to ionizing radiation. MAIN METHODS: Rats were allocated into four groups. First group served as control, the other three groups received gamma radiation (2 Gy/day) after 1 h of reserpine administration (1 ml/kg per day, s.c.) to induce FM for three successive days. On the next day, third and fourth groups received (30 mg/kg, p.o.) of PG and N-PG, respectively once daily for ten consecutive days. Tail flick test was performed and von Frey filaments were used to assess mechanical allodynia/hyperalgesia, and then rats were sacrificed to obtain brains. KEY FINDINGS: N-PG effectively replenished reserpine effects and treated both allodynia and hyperalgesia, improved thermal allodynia, effectively recovered all neurotransmitters near to normal baseline, inhibited oxidative stress status via decreasing malondialdehyde (MDA), increasing glutathione (GSH) and superoxide dismutase (SOD), it had strong anti-inflammatory effect as verified by reducing both cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-kB) in addition to inhibition of intrinsic apoptosis through caspase-3 (casp-3) decrease and B-cell lymphoma-2 (Bcl-2) increase. Histopathological and immunohistochemical results confirmed the biochemical findings. SIGNIFICANCE: N-PG could be a promising drug for treating FM especially when there is urgent need to expose patient to ionizing radiation.

Morphological and mechanical properties of cervical muscles in fibromyalgia with migraine: A case-control study.

BACKGROUND: The precise manner in which morphological and mechanical properties of cervical muscles in patients with fibromyalgia and migraine are affected remains unclear. OBJECTIVES: The objective of this study was to compare the morphological and mechanical properties of cervical muscles in individuals diagnosed with fibromyalgia who also experience migraine headaches with those who do not. METHODS: The study included two groups of fibromyalgia patients: one with migraine (n = 18, age = 44.7 ± 7.5 years, body mass index = 28.7 ± 6.9 kg/m2) and one without migraine (n = 21, age = 42.6 ± 9.5 years, body mass index = 25.1 ± 4.4 kg/m2). Body pain intensity related to fibromyalgia and migraine attack severity were evaluated with a Visual Analog Scale (VAS). The cervical muscle morphological and mechanical properties, including thickness, cross-sectional area (CSA), and stiffness, were measured using ultrasound imaging. RESULTS: It was found that there was a greater decrease in longus colli muscle CSA scores (p = 0.004) and a greater increase in upper trapezius muscle stiffness scores (p = 0.013) in the fibromyalgia + migraine group compared to the fibromyalgia group. No statistically significant differences were observed in trapezius muscle thickness (p = 0.261), sternocleidomastoid muscle thickness (p = 0.874), multifidus CSA (p = 0.963), or sternocleidomastoid muscle stiffness (p = 0.642) between the two groups. CONCLUSION: Patients with fibromyalgia and migraine exhibited diminished longus colli muscle CSA and heightened upper trapezius muscle stiffness compared to those with fibromyalgia but no migraine. It should be considered that migraine comorbidity in fibromyalgia may negatively affect cervical muscle morphological and mechanical properties.

Recognizing and Treating Major Depression in Fibromyalgia: A Narrative Primer for the Non-Psychiatrist.

Fibromyalgia (FM) affects 2% to 8% of the general population. FM patients often experience self-stigma and feel rejected by healthcare providers and families, resulting in isolation and distressing symptoms of pain, fatigue, and poor cognitive functioning, increasing the risk of depressive symptoms. Major Depressive Disorder (MDD) is the most common comorbidity in FM patients (Any depression: 43%; MDD: 32%). Genome-wide association studies (GWAS) have identified a common genetic risk loci for major depression and fibromyalgia. Given that even minor symptoms of depression worsen the outcomes of FM patients, clinicians are challenged to identify and manage depression in these patients. However, due to overlapping symptoms, limited screening, and contamination bias, MDD often goes undiagnosed and presents a critical challenge. Unrecognized and untreated MDD in FM patients can exacerbate fatigue, sleep disturbances, and pain, reduce physical functioning, and increase the risk of developing comorbid conditions, such as substance abuse and cardiovascular disease. These comorbidities are associated with a lower treatment response rate, a higher dropout rate, and a greater risk of relapse. Clinicians may effectively identify and treat MDD in FM patients with appropriate pharmacologic agents combined with aerobic exercise and cognitive-behavioral therapies for core FM symptoms, thus significantly reducing symptom severity for both MDD and FM. Such a comprehensive approach will result in a much-improved quality of life. MedLine content was searched via PubMed to identify eligible articles between 1995 and 2023 using search terms fibromyalgia, major depressive disorder, and treatment of depression in fibromyalgia, and the most current information is presented. In this primer for clinicians caring for FM patients, we describe clinically relevant pharmacologic and non-pharmacologic management approaches for treating MDD in FM patients.

Somatisation differentiates fibromyalgia from low back pain: a comparative, cross-sectional cohort study.

OBJECTIVES: To examine whether somatisation, depression, anxiety, fatigue, coping dimensions, pain, physical and social function, or sociodemographic characteristics can differentiate fibromyalgia from low back pain in a cross-sectional cohort setting of our Zurzach Interdisciplinary Pain Programme. METHODS: Fibromyalgia and low back pain (not fulfilling the diagnostic criteria for fibromyalgia) were compared using the Symptom Checklist-90R (SCL-90R) Somatisation scale, the Quantification Inventory for Somatoform Syndromes (QUISS) Number of somatoform symptoms, and other standardised instruments. Standardised mean differences (SMDs) quantified the score differences, and binomial logistic regression modelling with various co-variates differentiated fibromyalgia from low back pain. RESULTS: The largest differences indicating worse health in fibromyalgia (n = 131) were in somatisation (SCL-90R: SMD=-0.971, QUISS: SMD=-0.960), followed by affective health, pain and coping (SMDs between -0.632 and -0.280). Physical and social functioning were comparable in the two conditions (n = 262 low back pain). The two somatisation scales both with odds ratios (OR)=0.966 (p≤ 0.002) plus female sex (OR = 3.396, p< 0.001) predicted 74.3% of the cases correctly (accuracy) with a positive predictive value of 65.3% and a specificity of 87.0% for fibromyalgia. In the female subsample (n = 280), the model remained stable with an accuracy of 71.9%. CONCLUSION: Somatisation stood out from all other somatic, psychosocial, and coping dimensions and sociodemographics as the one significant specific predictor distinguishing fibromyalgia from low back pain. The fibromyalgia phenotype is characterised by the generalisation of painful loci but equally prominently by generalised somatoform symptoms. Assessment of somatisation is recommended to ensure accurate identification and understanding of the multifaceted syndrome of fibromyalgia.

Connecting the dots: Network structures of internalizing and functional symptoms in a population-based cohort.

OBJECTIVE: Comorbidities between internalizing disorders (IDs) and functional disorders (FDs) are well-documented, indicating shared pathways. However, their symptom-level relationships have been largely unexplored. This exploratory study employs a network approach to investigate symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS) to identify bridge symptoms explaining comorbidity between the two domains. METHODS: We used cross-sectional data on 72,919 adult subjects from the Lifelines Cohort Study, a Dutch general population sample. A total of 38 symptoms representing diagnostic criteria of IDs and FDs were assessed with validated questionnaires. Network models were estimated using eLasso, based on the Ising model, to identify bridge symptoms. The Network Comparison Test (NCT) was used to test whether there were differences in network structure and strength across sex and age. RESULTS: Symptoms were moderately connected, with a network density of 52.7%. ID and FD symptoms clustered in their respective domains, but were connected through the bridge symptoms, fatigue, difficulty concentrating, trouble sleeping, and unrefreshing sleep. Fatigue and difficulty concentrating had the most connections, associated with 86.6% and 78.9% of the other symptoms, respectively. NCTs indicated no differences in network connectivity between females versus males or younger versus older adults (>50 years). CONCLUSIONS: ID and FD symptoms are moderately interconnected. Bridge symptoms displaying strong connections to multiple disorders may play a central role in the mechanisms underpinning the comorbidity between IDs and FDs.

Amitriptyline and duloxetine attenuate activities of superficial dorsal horn neurons in a rat reserpine-induced fibromyalgia model.

Fibromyalgia (FM) is an intractable disease with a chief complaint of chronic widespread pain. Amitriptyline (AMI) and duloxetine (DLX), which are antidepressant drugs, have been reported to ameliorate pain in patients with FM and pain-related behaviors in several rodent models of FM. However, the mechanisms of action of AMI and DLX are not yet fully understood. Here, we examined the effects of these drugs on the responsiveness of superficial dorsal horn (SDH) neurons in the spinal cord, using a rat FM model developed by injecting a biogenic amine depleter (reserpine). Extracellular recordings of SDH neurons in vivo demonstrated that bath application of AMI and DLX at concentrations of 0.1-1.0 mM on the dorsal surface of the spinal cord markedly suppressed spontaneous discharge and von Frey filament-evoked mechanical firing in SDH neurons. The suppression induced by the drugs was noted in a concentration-dependent manner and the suppressive effects resolved after washing the spinal cord surface. These results show that SDH neurons are the site of action for AMI and DLX in a rat reserpine-induced FM model. Spinal mechanisms may underlie the therapeutic effects of these drugs in patients with FM.