Background: This study investigates the psychological underpinnings of chronic pain conditions, specifically fibromyalgia, chronic headache, vulvodynia, and mixed condition (consisting of fibromyalgia in comorbidity with chronic headache and/or vulvodynia), with a focus on nociplastic pain mechanisms.Objective: The aim of the study is to better understand the psychological functioning of women with different chronic pain conditions to identify and discuss similarities and differences. In particular, we aim to explore any significant differences in the domain of traumatic experiences, in global defensive functioning, and in the domain of alexithymia among the evaluated groups. Further, the 4 groups with chronic pain will be compared with a healthy control group.Methods: A sample of 1006 Italian women diagnosed with chronic pain participated in the study, categorized into four clinical groups and a healthy control group. Measures were assessed using self-report measures, in particular: Traumatic Experiences Checklist, Defense Mechanism Rating Scales, and Toronto Alexithymia Scale.Results: There are significant differences among groups, with mixed conditions exhibiting the highest levels of traumatic experiences, particularly emotional neglect and physical threats. Fibromyalgia and mixed condition groups displayed greater reliance on neurotic defense mechanisms. Additionally, fibromyalgia and mixed condition participants exhibited higher levels of alexithymia, indicating difficulties in emotional processing.Conclusions: These findings underscore the complex interplay between psychological factors and nociplastic pain conditions, emphasizing the importance of personalized psychological interventions in managing nociplastic pain. The study highlights the need for multidisciplinary approaches to nociplastic pain treatment, considering the diverse psychological profiles of affected individuals.

Chronic primary pain including fibromyalgia for the musculoskeletal system persists for more than 3 months. Its etiological factors and the pathophysiological mechanisms are not known, and therefore, there is no satisfactory therapy, it is an unmet medical need condition. The only etiological and aggravating factor is chronic psychosocial distress, which is known to cause neuroimmune and endocrine changes both in the periphery and the central nervous system. In this short review, we introduce our research perspective by summarizing the recent literature on the interactions between chronic pain, stress, and commonly co-morbid mood disorders. Immune activation, autoimmunity, neuro-immune-vascular crosstalks and neuroinflammation play roles in the pathophysiology of these conditions. Data on stress-induced neuroplasticity changes at cellular and molecular levels were also collected in relation to chronic primary pain both from clinical studies and animal experiments of translational relevance. Understanding these mechanisms could help to identify novel therapeutic targets for chronic primary pain including fibromyalgia.

Low peak alpha frequency (PAF) is an electroencephalography (EEG) outcome associated reliably with high acute pain sensitivity. However, existing research suggests that the relationship between PAF and chronic pain is more variable. This variability could be attributable to chronic pain groups typically being examined as homogenous populations, without consideration being given to potential diagnosis-specific differences. Indeed, while emerging work has compared individuals with chronic pain to healthy controls, no previous studies have examined differences in PAF between diagnoses or across chronic pain subtypes.

To address this gap, we reanalysed a dataset of resting state EEG previously used to demonstrate a lack of difference in PAF between individuals with chronic pain and healthy controls. In this new analysis, we separated patients by diagnosis before comparing PAF across three subgroups: chronic widespread pain (n = 30), chronic back pain (n = 38), and healthy controls (n = 87).

We replicate the original finding of no significant difference between chronic pain groups and controls, but also find that individuals with widespread pain had significantly higher global average PAF values than those of people with chronic back pain [p = 0.028, β = 0.25 Hz] after controlling for age, sex, and depression.

These novel findings reveal PAF values in individuals with chronic pain may be diagnosis-specific and not uniformly shifted from the values of healthy controls. Future studies should account for diagnosis and be cautious with exploring homogenous 'chronic pain' classifications during investigations of PAF.

Our work suggests that, contrary to previous hypotheses, inter-individual differences in PAF reflect diagnosis-specific mechanisms rather than the general presence of chronic pain, and therefore may have important implications for future work regarding individually-tailored pain management strategies.

Fibromyalgia, characterized as a complex chronic pain syndrome, presents with symptoms of pervasive musculoskeletal pain, significant fatigue, and pronounced sensitivity at specific anatomical sites. Despite extensive research efforts, the origins of fibromyalgia remain enigmatic. This narrative review explores the intricate relationship between muscle oxygen saturation and fibromyalgia, positing that disruptions in the oxygenation processes within muscle tissues markedly influence the symptom profile of this disorder. Muscle oxygen saturation, crucial for muscle function, has been meticulously investigated in fibromyalgia patients through non-invasive techniques such as near-infrared spectroscopy and magnetic resonance imaging. The body of evidence consistently indicates substantial alterations in oxygen utilization within muscle fibers, manifesting as reduced efficiency in oxygen uptake during both rest and physical activity. These anomalies play a significant role in fibromyalgia's symptomatology, especially in terms of chronic pain and severe fatigue, potentially creating conditions that heighten pain sensitivity and accumulate metabolic byproducts. Hypothesized mechanisms for these findings encompass dysfunctions in microcirculation, mitochondrial irregularities, and autonomic nervous system disturbances, all meriting further research. Understanding the dynamics of muscle oxygen saturation in fibromyalgia is of paramount clinical importance, offering the potential for tailored therapeutic approaches to alleviate symptoms and improve the quality of life for sufferers. This investigation not only opens new avenues for innovative research but also fosters hope for more effective treatment strategies and improved outcomes for individuals with fibromyalgia.

The objective of this study was to conduct a comprehensive comparison of the effects of hip and knee strengthening training in patients with patellofemoral pain (PFP). A meta-analysis was conducted to investigate the effects of these two types of strengthening training on patients' lower limb biomechanics, knee pain and function. The aim was to evaluate the effectiveness of the two training modalities and provide evidence-based recommendations for the rehabilitation of patients with PFP. A total of 12 studies were identified through a search of the Web of Science, EBSCO, and PubMed databases. The selected studies comprised nine randomized controlled trials (RCTs), one comparative controlled trial (CCTs) and two cohort studies (CSs), with a total of 1,066 patients. The quality of the included studies was evaluated via the PEDro scale, and a meta-analysis was conducted via Stata18 software. The results show that both types of strengthening training positively impact pain reduction and improved knee function in PFP patients. Moderate evidence from meta-analyses indicated that hip strengthening training (SMD = -1.740, 95%; CI -2.212 to -1.267, P < 0.001) was more effective than knee strengthening training (SMD = -1.302, 95%; CI -1.75 to -0.86, P < 0.001) in reducing pain (VAS). Similarly, Strong evidence suggests that hip strengthening training (SMD = 1.205, 95%; CI 0.968 to 1.443, P < 0.001) was significantly more effective than knee strengthening training (SMD = 1.023, 95%; CI 0.722 to 1.325, P < 0.001) in improving knee function (AKPS). Additionally, moderate evidence suggests that hip strengthening training significantly increased hip abductor strength (SMD = 0.848, 95%; CI 0.508-1.187, P < 0.001) and external rotator strength (SMD = 0.780, 95%; CI 0.416-1.145, P < 0.001), while strong evidence suggests that knee strengthening training did not significantly enhance knee extensor strength (SMD = 0.212, 95%; CI -0.014 to 0.439, P = 0.066). Therefore, clinicians should use hip strengthening as one of the primary training interventions when treating patients with PFP.

Autoimmunity and immunoglobulin G (IgG) autoantibodies may contribute to pain in a subset of fibromyalgia (FM) patients. Previously, IgG from FM patients was found to induce pain-like behavior in mice and bind to satellite glial cells (anti-SGC IgG). The anti-SGC IgG levels were also associated with more severe symptomatology. Lipid metabolism in FM subjects is altered with lysophosphatidylcholines (LPCs) acting as pain mediators. The relationship between autoantibodies, lipid metabolism, and FM symptomatology remains unclear. Serum lipidomics with liquid chromatography mass spectrometry, anti-SGC IgG levels, and clinical measures were examined in 35 female FM subjects and 33 age- and body mass index-balanced healthy controls (HC). Fibromyalgia subjects with higher anti-SGC IgG levels experienced more intense pain than those with lower levels. Sixty-three lipids were significantly altered between FM subjects and HC or between FM subjects with severe (FM severe) and mild symptoms (FM mild). Compared to HC, FM subjects had lower concentrations of lipid species belonging to the classes LPC (n = 10), lysophosphatidylethanolamine (n = 7), phosphatidylcholine (n = 4), and triglyceride (n = 5), but higher concentrations of diglyceride (n = 3). Additionally, FM severe had higher LPC 19:0, 22:0, and 24:1 and lower sphingomyelin (n = 9) concentrations compared to FM mild. Positive associations were seen for LPC 22:0 and 24:1 with pain intensity and anti-SGC IgG levels in FM subjects. Taken together, these results suggest an association between altered lipid metabolism and autoimmune mechanisms in FM.

Fibromyalgia has a high female predominance and research work has been focussing mainly on women.

We aimed to answer (1) gender differences in pain scores and quality of life, (2) any gender-specific subgroups defined by quantitative sensory testing (QST), and (3) correlations of QST parameters with pain intensity and questionnaire scores.

We evaluated clinical presentations and QST profiles from 38 male and 38 age-matched female patients.

Women reported significantly higher scores in average daily pain, daily sleep interference score, average weekly pain, weekly sleep interference score, and revised fibromyalgia impact questionnaire (rFIQ). Based on LOGA classification, L0G2, mechanical allodynia or hyperalgesia without abnormal sensory loss, was the most common QST subtype which accounted for 28.9% of men and 26.3% of women. Approximately 34.2% of men and 26.3% of women displayed loss of function of small fibres with an increased cold or warm detection threshold. Cold detection threshold was negatively correlated with pain intensity and functional impairment, suggesting a peripheral mechanism. Central sensitization, defined as allodynia and hyperalgesia to thermal or mechanical stimuli, was found in two-thirds of male and female patients. Mechanical pain sensitivity was positively correlated with the severity of pain and associated symptoms in women, but not men.

There was a marked gender difference in reported pain and quality of life. We have confirmed that central sensitization is a major mechanism for women. Our data suggested an important role of small fibre pathology in both men and women.

Fibromyalgia Syndrome (FMS) predominantly affects middle-aged women, characterized by musculoskeletal pain, fatigue, and cognitive issues. Choline, an endogenous molecule, may influence FMS due to its analgesic and anti-inflammatory properties. This study compared choline, leptin, and interleukin-6 (IL-6) levels in FMS patients and controls and examining their association with pain severity.

Volunteers with FMS were clinically diagnosed at a Physical Medicine and Rehabilitation Department. The control group included pain-free volunteers. Pain severity was gauged using a numeric scale, dietary choline intake through a questionnaire. Serum choline, leptin and (interleukin)IL-6 levels were measured from fasting blood samples of volunteers with enzyme-linked immunosorbent assays (ELISA).

All FMS patients (n = 38) and healthy volunteers (n = 38) were female. Pain score in patients with FMS was 7.6 ± 0.2. Dietary choline intake was lower in patients with FMS than the controls (p = 0.036). Serum choline and leptin levels were lower in the FMS group compared to control (p = 0.03). Serum IL-6 levels were higher in the FMS group than in the control (p < 0.001). There was weak positive correlation between IL-6 levels and pain scores and there were no correlation between leptin levels and pain scores in FMS.

This research highlights FMS's complex nature, involving neurochemical, immunological, and nutritional factors. It suggests the significance of choline's anti-inflammatory effect, leptin's metabolic function, and IL-6's role in FMS pathology. The results suggest that reduced dietary choline might influence serum choline, leptin, and IL-6 levels, potentially impacting FMS-related pain. This points to the potential of supplementary choline intake in FMS management.

Not applicable (Non-interventional study).

Stress is widely recognized as the primary environmental factor associated with chronic pain conditions, including fibromyalgia. A recent study demonstrated the potential antinociceptive effects of 4-amino-3-(phenylselanyl) benzenesulfonamide (4-APSB) in acute nociceptive animal models due to its antioxidant and anti-inflammatory properties. However, the efficacy of 4-APSB in managing chronic painful conditions, such as fibromyalgia, has not been explored so far. This study investigated the pharmacological effects of 4-APSB in an experimental model of fibromyalgia induced by intermittent cold stress (ICS). Male and female mice were divided into Control, ICS, 4-APSB, and ICS + 4-APSB. After the ICS, the animals were treated with 4-APSB (1 mg kg-1) or vehicle by the intragastric route until the tenth day. The behavioral tasks were performed on days 5, 8, and 10. The findings showed a negative correlation between paw withdrawal threshold and Nrf2 or NFκB mRNA expression levels caused by ICS exposure. The 4-APSB suppressed the nociceptive signs and a depressive like-phenotype in male and female mice exposed to ICS. 4-APBS normalized the elevated levels of TBARS and the up-regulation of Nrf2 and NFκB expression in the cerebral cortex of ICS-exposed mice. This compound also modulated the oxidative stress in the spinal cord of female mice. The 4-APSB attenuated the inhibition of Na+, K+ - ATPase activity in the central nervous system (CNS) of female mice exposed to ICS. 4-APSB attenuated behavioral and redox imbalance triggered by the ICS model in male and female mice, suggesting its beneficial effects for treating fibromyalgia in both sexes.

The study aims to evaluate the effects of virtual reality (VR) programs on disease activity, central sensitization, kinesiophobia, body awareness, and pain catastrophizing in patients with fibromyalgia syndrome (FMS). Twenty-nine with FMS were randomized into the VR group or the control group (CG). FMS patients in the VR group were included in the VR-based relaxing treatment for 4 weeks, with one session per week. The progressive muscle relaxation technique and the breath-counting exercise were taught to participants in the CG. The Fibromyalgia Impact Questionnaire (FIQ), Central Sensitization Inventory Short-Form (CSI-SF), TAMPA, Pain Catastrophizing Scale (PCS), and Body Awareness Questionnaire (BAQ) were evaluated. Additionally, in the VR group, the Galvanic Skin Response (GSR), Simulator Sickness Questionnaire (SSQ), pain, stress, and exhaustion were assessed during each session. Post-treatment, the VR group showed significantly greater improvements than the CG in FIQ, CSI-SF, PCS, and BAQ (p < 0.05). Effect sizes in the VR group, except for TAMPA, ranged from large to very large (Cohen's d = 0.993-1.350). Although GSR scores decreased post-treatment, this reduction was not statistically significant (p > 0.05). Additionally, symptoms of SSQ, pain, stress, and exhaustion were notably reduced in the VR group. we recommend the widespread use of this innovative treatment approach in FMS patients.

Fatigue is a common health problem in older adults. Chronic pain is associated with fatigue. However, the longitudinal association between chronic pain and the incidence of subjective fatigue among community-dwelling older adults remains unclear. Therefore, this study aimed to investigate the association between chronic pain and subjective fatigue using prospective data.

The study included 2060 community-dwelling older adults (age 70.5 ± 6.4 years; male: n = 944) without subjective fatigue at baseline. Chronic pain and other data were assessed at baseline. Subjective fatigue incidence was investigated at the follow-up examination 2.5 years from baseline.

In total, 389 (18.9%) reported chronic low back pain, 322 (15.6%) reported chronic knee pain at baseline, and 342 (16.6%) reported subjective fatigue at follow-up examination. A logistic regression analysis showed that the odds ratio for the incidence of subjective fatigue in participants with chronic low back pain had a higher odds ratio for the incidence of subjective fatigue compared to participants without chronic low back pain (odds ratio = 1.71, 95% confidence interval = 1.29-2.26). Chronic knee pain had a higher odds ratio for the incidence of subjective fatigue compared to participants without chronic knee pain (odds ratio = 1.63, 95% confidence interval = 1.21-2.20).

These results suggest that chronic low back pain and knee pain increase the risk of subjective fatigue incidence. These findings emphasize the contribution of chronic pain to fatigue among older adults. Therefore, intervention studies are required to prevent subjective fatigue in participants with chronic pain. Geriatr Gerontol Int 2025; ••: ••-••.

This study investigates the associations between early childhood adversities, stress perception, and fibromyalgia syndrome (FMS). Although the interconnection between dysregulated stress systems and FMS is well documented, the interconnection between early adversities and FMS remains less understood. This study explores the relationship of early-life stress and FMS by examining its mediation through perceived stress, and acute and chronic endocrine stress indicators. Stress was assessed using the perceived stress scale, as well as using salivary and hair cortisol as endocrine indicators of acute and chronic stress, respectively. The sample consisted of 99 individuals with FMS and 50 pain-free controls. A structural equation model was used to assess the mediating effects of stress indicators between early adversities and the severity of FMS. Compared with controls, individuals with FMS had notably higher early adversity scores (d = 0.63) and greater occurrence of exposure to adversity (78.8% vs 66%). Structural equation modeling indicated that the influence of early adversities on FMS symptoms is mediated by perceived stress levels, with no direct effect observed. Our findings indicate that early-life adversity is a significant determinant of the development of FMS, with the relationship between these factors mediated by perceived stress rather than by endocrine stress indicators. These results underscore the critical role of stress perception in the development and management of FMS, suggesting that perceived stress may serve as a valuable therapeutic target. Incorporating trauma-informed and stress-targeted care into treatment strategies could significantly improve outcomes for individuals with FMS, emphasizing the importance of addressing psychological factors alongside physical symptoms.

Chronic widespread musculoskeletal pain (CWP), a significant health issue affecting individuals and society, is often diagnosed as part of fibromyalgia but is not generally considered inflammatory. This study investigated the relationship between blood-based inflammatory factors and CWP in 904 individuals from the TwinsUK cohort. Participants, free of major inflammatory conditions, completed questionnaires to assess CWP. Plasma samples were analysed using the Olink panel, alongside assays for C-reactive protein (CRP) and Apolipoproteins A1 and B. No significant associations were observed between CWP and inflammatory factors after adjusting for multiple testing. Twin modelling revealed significant heritability for both CWP and inflammatory factors, with genetic covariance observed between CWP and several inflammatory factors. Additive Bayesian network modelling suggested that any association between CWP and inflammatory factors is mediated by body mass index (BMI). These findings emphasize the complexity of CWP and its potential reliance on factors beyond inflammation, such as BMI, which strongly correlates with CRP and other inflammatory markers. Future research should explore additional molecular, genetic, and environmental contributors to CWP variability and investigate clinical factors or covariates that may obscure relationships with inflammation, providing a more comprehensive understanding of this multifaceted condition.

Chronic pain is a prevalent and debilitating condition whose neural mechanisms are incompletely understood. An imbalance of cerebral excitation and inhibition (E/I), particularly in the medial prefrontal cortex (mPFC), is believed to represent a crucial mechanism in the development and maintenance of chronic pain. Thus, identifying a non-invasive, scalable marker of E/I could provide valuable insights into the neural mechanisms of chronic pain and aid in developing clinically useful biomarkers. Recently, the aperiodic component of the electroencephalography (EEG) power spectrum has been proposed to represent a non-invasive proxy for E/I. We, therefore, assessed the aperiodic component in the mPFC of resting-state EEG recordings in 149 people with chronic pain and 115 healthy participants. We found robust evidence against differences in the aperiodic component in the mPFC between people with chronic pain and healthy participants, and no correlation between the aperiodic component and pain intensity. These findings were consistent across different subtypes of chronic pain and were similarly found in a whole-brain analysis. Their robustness was supported by preregistration and multiverse analyses across many different methodological choices. Together, our results suggest that the EEG aperiodic component does not differentiate between people with chronic pain and healthy individuals. These findings and the rigorous methodological approach can guide future studies investigating non-invasive, scalable markers of cerebral dysfunction in people with chronic pain and beyond.

Background: Fibromyalgia (FM) is a complex condition marked by increased pain sensitivity and central sensitization. Studies often explore the link between FM and depressive anxiety disorders, but few focus on dysthymia or persistent depressive disorder (PDD), which can be more disabling than major depression (MD). Objective: To identify clinical scales and subscales of the Personality Assessment Inventory (PAI) that effectively describe and differentiate the psychological profile of PDD, with or without comorbid MD, in FM patients with PDD previously dimensionally classified by the Millon Clinical Multiaxial Inventory III (MCMI-III). Method: An observational, cross-sectional study was conducted with 66 women (mean age 49.18, SD = 8.09) from Hospital del Mar. The PAI, the MCMI-III, and the Fibromyalgia Impact Questionnaire (FIQ) were used to assess the sample. Results: The PAI showed strong discriminative ability in detecting PDD, characterized by high scores in cognitive and emotional depression and low scores in identity alteration, dominance, and grandeur. High scores in cognitive, emotional, and physiological depression, identity alteration, cognitive anxiety, and suicidal ideation, along with low scores in dominance and grandeur, were needed to detect MD with PDD. Discriminant analysis could differentiate 69.6-73.9% of the PDD group and 84.6% of the PDD+MD group. Group comparisons showed that 72.2% of patients with an affective disorder by PAI were correctly classified in the MCMI-III affective disorder group, and 70% without affective disorder were correctly classified. Conclusions: The PAI effectively identifies PDD in FM patients and detects concurrent MD episodes, aiding in better prognostic and therapeutic guidance.

Whether fibromyalgia burden is related to measures of sensitization, assessed by quantitative sensory testing (QST), is not clear. We examine the associations between sensitization and fibromyalgia disease burden as measured by the polysymptomatic sistress scale (PDS) and the fibromyalgia impact questionnaire (FIQ) (range 0-100).

Participants were recruited from referrals to a rheumatology outpatient clinic and the fibromyalgia diagnosis was verified by a rheumatologist. They completed the PDS and FIQ and underwent QST of pressure pain threshold (PPT) at five sites, temporal summation (TS), and conditioned pain modulation (CPM) estimated as post-stimuli/pre-stimuli PPT. The associations between QST and disease burden were analysed in linear regression models adjusted for age, sex, and body mass index.

A total of 78 individuals with clinically verified fibromyalgia (90% women, mean age 40.9 years (SD 7.3)) were recruited. Overall mean PPT was associated with the FIQ total score (β-2.1, 95% CI-4.3, -0.0) and the function component (β-2.1, (-4.3, -0.0)). When examining the associations between PPT at individual sites and fibromyalgia disease severity, PPTs at the distal interphalangeal joint and tibialis anterior muscle were associated with both FIQ total score and the FIQ fatigue component. All associations were weak and insignificant after Bonferroni corrections.

In this cohort of individuals with fibromyalgia, sensitization was not significantly associated with self-reported disease burden. Our results point to the multifactorial nature of fibromyalgia disease severity.

In patients with fibromyalgia, commonly used measures of sensitization do not explain the symptom burden or the functional impact.

The multicomponent intervention FIBROWALK integrates pain science education (PSE), therapeutic exercise, cognitive behavioral therapy (CBT), and mindfulness training for treating fibromyalgia (FM). This study investigated the effects of the FIBROWALK in online (FIBRO-On) and outdoor (FIBRO-Out) formats compared to treatment-as-usual (TAU) on core clinical variables along with serum immune-inflammatory biomarkers and brain-derived neurotrophic factor (BDNF). Furthermore, the predictive value of these biomarkers on clinical response to FIBROWALK was also evaluated. 120 participants were randomly divided into three groups: TAU, TAU + FIBRO-On or TAU + FIBRO-Out. Clinical and blood assessments were conducted pre-post treatment. Both FIBRO-Out and FIBRO-On showed effectiveness (vs TAU) by improving functional impairment and kinesiophobia. Individuals allocated to FIBRO-Out (vs TAU) additionally showed decreases in pain, fatigue, depressive symptoms, and serum IL-6 and IL-10 levels along with IL-6/IL-4 ratio; patients allocated to FIBRO-On only showed a less stepped increase in IL-6 compared to TAU. An exaggerated pro-inflammatory profile along with higher levels of BDNF at baseline predicted greater clinical improvements in both active treatment arms. Our results suggest that FIBROWALK -in online and outdoor formats- is effective in individuals with FM and has significant immune regulatory effects in FM patients, while immune-inflammatory pathways and BDNF levels may in part predict its clinical effectiveness. Trial registration number NCT05377567 (clinicaltrials.gov).

Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain, fatigue and tenderness and closely associated with high levels of stress. FMS is therefore often considered a stress-related disease. A comparative study was conducted with 99 individuals diagnosed with FMS and a control group of 50 pain-free individuals. Stress indicators were classified into three categories: perceived stress assessed using the Perceived Stress Scale, and daily average salivary cortisol and hair cortisol concentrations as indicators of acute and chronic stress levels related to the hypothalamic-pituitary-adrenal axis. Analysis of variance and covariance were used to identify group differences and the influence of covariates age, sex, and body mass index. Correlational analyses further elucidated the relationship between stress indicators and clinical symptoms. Participants with FMS reported significantly higher perceived stress levels than controls (p < .001, ηp2 = 0.3), which were positively correlated with symptom burden (r = .41, p < .001). In contrast, there were no significant differences in the endocrinological stress indicators salivary and hair cortisol between the groups (p > .05), nor were these indicators associated with clinical symptoms. The study highlights the central role of perceived stress in FMS, whereas endocrinological indicators did not differentiate FMS from controls. This finding calls for a nuanced approach to clinical assessment and therapeutic interventions tailored to patients with FMS, emphasizing the management of perceived stressors.

Despite remarkable advances in the management of RA, there are still unmet needs that rheumatologists need to address. In this review, we focused on difficult-to-treat RA (D2T RA) and late-onset RA (LORA), and summarized their characteristics and management. The prevalence of D2T RA is reported to be 6-28% and many factors have been identified as risk factors for D2T RA, including female sex, long disease duration, seropositivity for rheumatoid factor and anti-cyclic citrullinated peptide antibody and their high titer, baseline high disease activity, and comorbidities. D2T RA is broadly divided into inflammatory and non-inflammatory conditions, and clinical features differ according to background. A proportion of D2T RA can be managed with treatment modification, mainly with interleukin-6 receptor inhibitors or Janus kinase inhibitors, but some D2T RA patients have a poor prognosis; thus, the implementation of precision medicine by stratifying patients according to disease status is needed. In the aging society, the epidemiology of RA is changing and the prevalence of LORA is increasing worldwide. LORA has distinct clinical features compared with young-onset RA, such as acute onset, low seropositivity, and high inflammation. The pathogenesis of LORA remains to be elucidated, but proinflammatory cytokines, including interleukin-6, have been reported to be significantly elevated. LORA has several management concerns other than RA itself, such as geriatric syndrome and multimorbidity. The treat-to-target strategy is effective for LORA, but the evidence is still lacking; thus, it is important to accumulate clinical and related basic data to establish the optimal treatment strategy for LORA.

Fibromyalgia has many unmet needs relating to treatment, and the delivery of effective and evidence-based healthcare is lacking. We analyzed social media conversations to understand the patients' perspectives on the lived experience of fibromyalgia, factors reported to trigger flares of pain, and the treatments being discussed, identifying barriers and opportunities to improve healthcare delivery.

A non-interventional retrospective analysis accessed detail-rich conversations about fibromyalgia patients' experiences with 714,000 documents, including a fibromyalgia language tag, which were curated between May 2019 and April 2021. Data were analyzed via qualitative and quantitative analyses.

Fibromyalgia conversations were found the most on Twitter and Reddit, and conversation trends remained stable over time. There were numerous environmental and modifiable triggers, ranging from the most frequent trigger of stress and anxiety to various foods. Arthritis and irritable bowel syndrome (IBS) were the most frequently associated comorbidities. Patients with fibromyalgia reported a wide range of symptoms, with pain being a cardinal feature. The massage, meditation and acupuncture domains were the most reported treatment modalities. Opportunities to improve healthcare delivered by medical providers were identified with current frustration relating to a lack of acknowledgement of their disease, minimization of symptoms and inadequately meeting their care needs.

We developed a comprehensive, large-scale study which emphasizes advanced natural language processing algorithm application in real-world research design. Through the extensive encapsulation of patient perspectives, we outlined the habitual symptoms, triggers and treatment modalities which provide a durable foundation for addressing gaps in healthcare provision.

To assess the association between fibromyalgia (FM) and insulin resistance (IR) using multiple IR indices in FM patients and to investigate how these indices vary with the severity of FM.

This cross-sectional study included 70 female patients diagnosed with FM and 70 age-matched female healthy controls. The data collected included demographics, clinical characteristics, and laboratory parameters. FM severity was evaluated using the Fibromyalgia Impact Questionnaire-Revised (FIQR). The metabolic indices calculated were the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI), triglyceride - glucose index (TyG), triglyceride to HDL cholesterol ratio (TG/HDL-C), and Metabolic Score for Insulin Resistance (METS-IR).

FM patients exhibited significantly higher HOMA-IR values (p = 0.002), and lower QUICKI values (p = 0.000) than controls. METS-IR also showed significant differences between FM patients and controls (p = 0.026). HOMA-IR and METS-IR values increased with FM severity, whereas QUICKI values decreased (p < 0.05). Duration of FM showed a moderately positive correlation with HOMA-IR (r = 0.249, p = 0.027). For TG/HDL-C and METS-IR, the correlations were weaker, but still positive (r = 0.094, p = 0.378, and r = 0.184, p = 0.056, respectively).

This study observed a significant association between FM and IR, as evidenced by metabolic indices in FM patients compared to controls. IR levels tended to increase with FM severity and duration. These findings suggest that IR could play a role in FM pathogenesis. Non-invasive and practical methods, such as METS-IR, may provide advantages for metabolic screening in FM patients; however, further studies are needed to establish their clinical utility.

Dry needling (DN) has been demonstrated as an effective treatment for patients with fibromyalgia (FM). It is crucial to take into consideration catastrophizing, a psychological construct that could potentially undermine the short-term efficacy of DN.

To analyze the effects of DN in the infraspinatus muscle on both local and remote pressure pain thresholds (PPTs) and its relationship with baseline levels of pain catastrophizing in patients with FM.

Randomized controlled trial.

All participants were randomly assigned to one of three interventions: DN, sham DN, and no intervention. Hong's fast-in and fast-out technique was implemented during the DN intervention.

The primary study outcome pain sensitivity (local and remote PPTs) was assessed at baseline, immediately post, and 24 h post intervention to evaluate short-term effect. Pain catastrophizing was measured at baseline in all participants using the Pain Catastrophizing Scale. To analyze the effect of DN on local and remote PPTs, an analysis of covariance was performed using catastrophism as covariate. Additionally, to examine the possible influence of catastrophism on local PPTs ratings in the subsequent assessment we performed a moderation analysis.

A total of 120 women diagnosed with FM. However, during the follow-up period, 24 participants discontinued their involvement, leaving a final cohort of 96 patients who successfully concluded the study.

DN showed significant differences in both local PPTs immediately post intervention and 24 h post intervention (MD [95% confidence interval] = 3.21 [0.40-6.02] kg/cm2, p = .019; and 2.84 [0.10-5.58] kg/cm2, p = .039, respectively) compared to sham and no-intervention groups. In addition, DN group results suggest that moderate values of catastrophizing (<35) diminish the effect of DN immediately postintervention.

The infraspinatus DN led to a notable reduction in local PPTs among individuals with FM. Additionally, the effectiveness of the DN treatment was influenced by pain catastrophizing.

Behavioral factors of pain catastrophizing and perceived injustice are associated with pain intensity in chronic pain. Diminished heart rate variability (HRV) is also strongly associated with chronic pain. These factors have been less explored earlier in the pain experience and it is unclear whether they play a role in the transition from acute to chronic pain. The aim of this study was to determine the relationship between pain catastrophizing, perceived injustice, pain intensity, and HRV in naturally occurring acute pain.

Ninety-seven patients were recruited from local outpatient physical therapy clinics. Seated HRV was captured on 94 patients via Polar chest strap while patients were taking a survey via iPad. In addition to sociodemographic data, the survey included the Pain Catastrophizing Scale (PCS), Injustice Experience Questionnaire (IEQ), and Numeric Pain Rating Scale (NPRS). The natural log of high-frequency power (lnHFP) HRV was used in the statistical analysis.

Multiple linear regression modeling revealed that lower pain catastrophizing, higher perceived injustice, and lower pain intensity were associated with lower HRV, and accounted for 11.4% of the variance in HRV.

While greater chronic pain intensity is associated with lower HRV, the relationship is reversed in the setting of acute pain. These findings highlight the need to better understand the unique factors that contribute to lower HRV in the acute phase.

Chronic pain causes disability and loss of health worldwide. Yet, a mechanistic explanation for it is still missing. Frequently, neural phenomena, and among them, Central Sensitization (CS), is presented as causing chronic pain. This narrative review explores the evidence substantiating the relationship between CS and chronic pain: four expert researchers were divided in two independent teams that reviewed the available evidence. Three criteria were established for a study to demonstrate a causal relationship: (1) confirm presence of CS, (2) study chronic pain, and (3) test sufficiency or necessity of CS over chronic pain symptoms. No study met those criteria, failing to demonstrate that CS can cause chronic pain. Also, no evidence reporting the occurrence of CS in humans was found. Worryingly, pain assessments are often confounded with CS measures in the literature, omitting that the latter is a neurophysiological and not a perceptual phenomenon. Future research should avoid this misconception to directly interrogate what is the causal contribution of CS to chronic pain to better comprehend this problematic condition.

Small fiber pathology may be involved in the pathophysiology of pain in women with fibromyalgia syndrome (FMS).

This prospective single-center case-control study provides detailed pain phenotyping and small fiber pathology data in a cohort of men with FMS on a morphological and functional level.

Forty-two men with FMS underwent a comprehensive pain-related interview and neurological examination, a questionnaire and neurophysiological assessment, and specialized small fiber tests: skin punch biopsy, quantitative sensory testing including C-tactile afferents, and corneal confocal microscopy. Data were compared with those of healthy male controls.

Men with FMS reported generalized and permanent pain with additional pain attacks and a mostly pressing pain character. Intraepidermal nerve fiber density was reduced at ≥1 biopsy site in 35 of 42 (83%) men with FMS (controls: 32/65, 49%). Compared with male controls, men with FMS had elevated cold (P < 0.05) and warm detection thresholds (P < 0.001) and an increased mechanical pain threshold (P < 0.05) as well as an impairment of C-tactile afferents (P < 0.05). Corneal nerve fiber density was lower in male patients with FMS vs healthy men (P < 0.01). Male FMS patients with pathological skin innervation at ≥1 biopsy site compared with those with normal skin innervation had a higher clinical Widespread Pain Index (P < 0.05) indicating an association between the severity of cutaneous denervation and symptom load.

We show a distinct pain phenotype and small nerve fiber dysfunction and pathology in male patients with FMS. These findings may have implications for the diagnosis and management of men with FMS.

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.

Nociplastic pain, a third mechanistic pain descriptor in addition to nociceptive and neuropathic pain, was adopted in 2017 by the International Association for the Study of Pain (IASP). It is defined as "pain that arises from altered nociception" not fully explained by nociceptive or neuropathic pain mechanisms. Peripheral and/or central sensitization, manifesting as allodynia and hyperalgesia, is typically present, although not specific for nociplastic pain. Criteria for possible nociplastic pain manifesting in the musculoskeletal system define a minimum of 4 conditions: (1) pain duration of more than 3 months; (2) regional, multifocal or widespread rather than discrete distribution of pain; (3) pain cannot entirely be explained by nociceptive or neuropathic mechanisms; and (4) clinical signs of pain hypersensitivity present in the region of pain. Educational endeavors and field testing of criteria are needed. Pharmacological treatment guidelines, based on the three pain types, need to be developed. Currently pharmacological treatments of nociplastic pain resemble those of neuropathic; however, opioids should be avoided. A major challenge is to unravel pathophysiological mechanisms driving altered nociception in patients suffering from nociplastic pain. Examples from fibromyalgia would include pathophysiology of the peripheral as well as central nervous system, such as autoreactive antibodies acting at the level of the dorsal root ganglia and aberrant cerebral pain processing, including altered brain network architecture. Understanding pathophysiological mechanisms and their interactions is a prerequisite for the development of diagnostic tests allowing for individualized treatments and development of new strategies for prevention and treatment.

Headache is one of the most common symptoms after a whiplash injury, although the pathophysiology remains under discussion. This study aimed to evaluate differences in neuropathic pain and central sensitization features between those who present with whiplash-associated headache (WAH) soon after a whiplash injury and those who do not.

This case-control study evaluated differences on the self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), Pain Detect Questionnaire (PDQ) and the Central Sensitization Inventory (CSI) between those who present with WAH in the acute phase after a whiplash injury (n = 46) and those who do not (n = 36). Moreover, the association of these variables in addition to neck pain intensity and the Neck Disability Index (NDI) score, with the presence of WAH was examined through logistic regression.

While differences between groups were found for both neuropathic and central sensitization features, only the presence of neuropathic pain features was associated with the presence of headache, with 27 scores for the S-LANSS and 23 for the PDQ from 46 people with headache (58.6% and 50.0%, respectively). The NDI and the S-LANSS partially explained (R2 = 0.68) the presence of WAH according to a logistic regression model.

Significant differences were found between people with whiplash with and without WAH when the S-LANSS, the PDQ and the CSI were assessed. S-LANSS and NDI were the variables most associated with the presence of WAH. These findings suggest that neuropathic pain features may be associated with the presence of acute WAH.

Fibromyalgia (FM) is a complex disorder involving pain dysregulation that can occur independently or alongside other rheumatological illnesses, complicating symptom interpretation. Consequently, this study aimed to evaluate the prevalence of secondary FM in patients with rheumatological diseases and its impact using the Revised Fibromyalgia Impact Questionnaire.

This cross-sectional descriptive study was conducted at the Rheumatology Outpatient Department of King Fahad Military Medical Complex, Dhahran, from August 2023 to October 2023. Patients with primary rheumatological diseases other than FM were recruited. Secondary FM was diagnosed based on the 2016 revisions of the 2010/2011 FM diagnostic criteria. Data on the demographics of patients were collected through self-reported questionnaires.

Overall, 158 women (76%) and 50 men (24%) with a mean age of 45.7 (12.8) years participated in the study. Systemic lupus erythematosus was the primary diagnosis for most patients. Fisher's exact test (p=0.007) indicated a significant but weak association between osteoarthritis and FM. A family history of comorbidity was significantly associated with an FM diagnosis (p<0.043). Having a major life event, such as the death of a kin, was significantly associated with FM (p<0.032). A personal history of functional disorders was significantly linked to a diagnosis of concomitant FM.

Concomitant FM is frequently undetected in patients with rheumatic diseases. Raising awareness of FM through educational programs may facilitate earlier diagnosis and more effective treatment.

To present an innovative integrated manualized psychotherapeutic intervention for fibromyalgia (FM) based on cognitive and behavioral therapy, acceptance and commitment therapy, and somatic experiential techniques (namely the INTEGRated Psychotherapeutic InterventiOn, INTEGRO) and illustrate its application on two case studies.

INTEGRO is composed of 12 individual sessions. The main objectives of the intervention were psychoeducation of chronic pain mechanisms, understanding the role of cognitive and emotional variables in one's pain perception, teaching patient-tailored skills to increase pain awareness and its management, and learning how to live with pain experience. A 57-year-old woman (patient A) and a 26-year-old woman (patient B) with FM have been selected to describe their care pathways connected to the INTEGRO protocol. Data related to assessment variables and clinical processes have been reported, focusing on the mechanisms that contribute to the maintenance (i.e., avoidance or overcompensation) of chronic pain in FM, on the role of patients' naïf theories, and on the implications that all these aspects may have on the burden related to pain management.

Both patients showed a reduction in FM burden and an increase in self-efficacy in pain management: patient A reported an improvement in emotional regulation ability; patient B showed a decrease in pain interference in work activities and on emotional dimension.

Examining each phase of the clinical protocol through the lens of its clinical application, the paper provides insights into the relationship among crucial psychosocial mechanisms, pain perception, management in FM treatment, and how all these aspects have been dealt with during psychotherapeutic treatment.

Functional somatic disorders (FSD) are common conditions that result in a significant deterioration of the quality of life. Their origin is multifactorial and poorly understood, and their management is often inadequately defined. Medications typically show limited effectiveness, while mind-body approaches play a central role, guided by three key principles: establishing an empathetic, respectful, and sincere doctor-patient relationship; promoting regular and gradual physical activity; and implementing cognitive behavioral therapy (CBT). Special attention must be devoted to establishing a trustworthy relationship between the physician and the patient. Recognizing the reality and severity of symptoms and providing a positive diagnosis as well as an explanatory model to account for them rationally are fundamental aspects of patient management. Cognitive and behavioral maintenance factors should be investigated and constitute therapeutic targets. Cognitive factors include focused attention on body functioning and catastrophizing. Patients frequently display avoidance behaviors, particularly in relation to physical exertion, and it is crucial to motivate them to reintroduce gradual physical activity customized to their abilities. This approach has demonstrated efficacy in improving fatigue, pain, and the physical and mental quality of life for patients with FSD. Among psychotherapeutic approaches, the benefit of CBT is well-established. The combination of gradual physical activity and CBT appears to be complementary. Other mind-body approaches such as mindfulness meditation might help although their level of evidence is weaker. Given the prevalence of FSD in the general population, it seems necessary for all physicians to be trained in managing this condition.

Opioid and cannabinoid therapies for chronic pain conditions including neuropathic pain are controversial. Understanding patient and prescribing factors contributing to risks and implementing risk mitigation strategies optimizes outcomes.

The ongoing transformation from a biomedical model of pain care toward a biopsychosocial model has been accompanied by a shift away from opioid therapy for pain, in particular for chronic pain. Opioid overdose deaths and opioid use disorder have greatly increased in the last several decades, initially because of increases in opioid prescribing and more recently associated with illicit drug use, in particular fentanyl derivatives. Opioid risk mitigation strategies may reduce risks related to opioid prescribing and tapering or discontinuation. Opioid therapy guidelines from the Centers for Disease Control and Prevention have become the consensus best practice for opioid therapy. Regulatory agencies and licensing medical boards have implemented restrictions and other mandates regarding opioid therapy. Meanwhile, interest in and use of cannabinoids for chronic pain has grown in the United States.

Opioid therapy is generally not recommended for the chronic treatment of neuropathic pain conditions. Opioids may be considered for temporary use in patients with severe pain related to selected neuropathic pain conditions (such as postherpetic neuralgia), and only as part of a multimodal treatment regimen. Opioid risk mitigation strategies include careful patient selection and evaluation, patient education and informed consent, querying the state prescription drug monitoring programs, urine drug testing, and issuance of naloxone as potential rescue medication. Close follow-up when initiating or adjusting opioid therapy and frequent reevaluation during long-term opioid therapy is required. There is evidence for the efficacy of cannabinoids for neuropathic pain, with meaningful response rates in select patient populations.

Nociplastic pain, characterized by abnormal pain processing without an identifiable organic cause, affects a significant portion of the global population. Unfortunately, current pharmacological treatments for this condition often prove ineffective, prompting the need to explore new potential targets for inducing analgesic effects in patients with nociplastic pain. In this context, toll-like receptors (TLRs), known for their role in the immune response to infections, represent promising opportunities for pharmacological intervention because they play a relevant role in both the development and maintenance of pain. Although TLRs have been extensively studied in neuropathic and inflammatory pain, their specific contributions to nociplastic pain remain less clear, demanding further investigation. This review consolidates current evidence on the connection between TLRs and nociplastic pain, with a specific focus on prevalent conditions like fibromyalgia, stress-induced pain, sleep deprivation-related pain, and irritable bowel syndrome. In addition, we explore the association between nociplastic pain and psychiatric comorbidities, proposing that modulating TLRs can potentially alleviate both pain syndromes and related psychiatric disorders. Finally, we discuss the potential sex differences in TLR signaling, considering the higher prevalence of nociplastic pain among women. Altogether, this review aims to shed light on nociplastic pain, its underlying mechanisms, and its intriguing relationship with TLR signaling pathways, ultimately framing the potential therapeutic role of TLRs in addressing this challenging condition.

Balneotherapy, using heated natural mineral waters at 36-38 °C, presents a comprehensive treatment approach for Fibromyalgia Syndrome (FMS). This study aims to assess the effect of balneotherapy in reducing pain intensity, disability, and depression in patients with FMS. We want to assess this effect at just four time-points: immediately at the end of the therapy, and at 1, 3, and 6 months of follow-up. Following PRISMA guidelines, we conducted an aggregate data meta-analysis, registered in PROSPERO CRD42023478206, searching PubMed Medline, Science Direct, CINAHL Complete, Scopus, and Web of Science until August 2023 for relevant randomized controlled trials (RCTs) that assess the effect of balneotherapy on pain intensity, disability, and depression in FMS patients. Methodological quality was assessed using the Cochrane methodology, and the pooled effect was calculated using Cohen's standardized mean difference (SMD) and its 95% confidence interval (95% CI) in a random-effects model. Sixteen RCTs were included in the meta-analysis. Balneotherapy is effective in reducing pain intensity (SMD - 1.67; 95% CI -2.18 to -1.16), disability (SMD - 1.1; 95% CI -1.46 to -0.7), and depression (SMD - 0.51; 95% CI -0.93 to -0.9) at the end of the intervention. This effect was maintained at 1, 3, and 6 months for pain intensity and disability. Balneotherapy improves both pain intensity and disability in patients with FMS, providing evidence that its positive effects are sustained for up to 6 months of follow-up. Nevertheless, it is important to note that the improvement in depression varies across different temporal phases.

Fibromyalgia is a chronic syndrome characterized by constant and generalized pain associated with sleep disturbance, depression, muscle stiffness, fatigue and cognitive disorders. Among non-pharmacological treatments, physical exercise stands out as a low-cost approach.

To summarize and analyze evidence on the effects of resistance training on pain, functionality and quality of life in women with fibromyalgia.

Following the PRISMA method, this systematic review included clinical trials assessing the effects of resistance training on pain, quality of life and functionality in female patients with fibromyalgia, regardless age. The researches were conducted in April 2021 in PubMed, Cochrane, Web of Science and Scopus databases, using the search strategy: ("fibromyalgia") AND ("strength training" OR "resistance training") AND ("quality of life" OR "pain" OR "functionality"). This study was registered in PROSPERO (CRD number: 42,021,246,245), and the risk of bias was assessed using the Version 2 of the Cochrane Risk-of-Bias tool (RoB 2).

The search resulted in 125 studies (760 women), of which 16 were eligible for this review. Risk of bias assessment resulted in high (n = 5), moderate (n = 6) and low (n = 5) risks. Resistance training has proven to be an important non-pharmacological treatment tool for fibromyalgia, reducing pain, and improving patients' functionality and quality of life.

The available evidence suggests that resistance training performed twice weekly, with progressive loads ranging from 40 to 80% of one-repetition maximum and a total duration of 4-24 weeks, appears to be an effective and safe therapeutic approach.

Fibromyalgia (FM) is a multifaceted disease that is often associated with neuropsychiatric disorders and is burdened by a high degree of psychological distress. Non-pharmacological interventions, including physical exercise and complementary therapies, have shown satisfactory results for either physical or psychological FM symptoms.

In this narrative review, we analyzed scientific evidence of moderate to high quality regarding the psychological and neurocognitive effects of physical therapies for FM. A total of 29 studies were selected after searching the PubMed and Google Scholar databases using the combination of terms « fibromyalgia», «psychological distress», «fibrofog», mental disorder», «aerobic exercise», «strength exercise», «Pilates», «Tai chi» and «Yoga».

Aerobic exercise can improve depression, anxiety, stress, mental function and mood, thanks to the remodulation of neurotransmitters and hormones. Strength training, on the other hand, has been shown to alleviate mental confusion, anger and depression. Finally, mind-body disciplines appear to be effective for depression, anxiety, catastrophizing, memory and coping strategies. Based on these findings, we devised an ideal exercise program that could relieve the psychological distress of FM patients, thus interrupting the pathogenic neuroendocrine circuits that lead to the exacerbation of pain and other FM-related symptoms.

Thanks to neuroendocrine remodulation, physical exercise may simultaneously improve the physical and mental health of FM patients. This narrative review collects current evidence on the effects of specific physical interventions on psychological and neurocognitive domains of FM patients and additionally provides an evidence-based training program that could be prescribed to FM patients with high psychological distress or neuropsychiatric symptoms.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating adverse effects caused by chemotherapy drugs such as paclitaxel, oxaliplatin and vincristine. It is untreatable and often leads to the discontinuation of cancer therapy and a decrease in the quality of life of cancer patients. It is well-established that neuroinflammation and the activation of immune and glial cells are among the major drivers of CIPN. However, these processes are still poorly understood, and while many chemotherapy drugs alone can drive the activation of these cells and consequent neuroinflammation, it remains elusive to what extent the gut microbiome influences these processes. In this review, we focus on the peripheral mechanisms driving CIPN, and we address the bidirectional pathways by which the gut microbiome communicates with the immune and nervous systems. Additionally, we critically evaluate literature addressing how chemotherapy-induced dysbiosis and the consequent imbalance in bacterial products may contribute to the activation of immune and glial cells, both of which drive neuroinflammation and possibly CIPN development, and how we could use this knowledge for the development of effective treatment strategies.

Fibromyalgia (FM) is a complex and poorly understood disorder characterized by chronic and widespread musculoskeletal pain, of which the etiology remains unknown. Now, the disorder of the gut microbiome is considered as one of the main causes of FM. This study aimed to investigate the potential benefits of fecal microbiota transplantation (FMT) in patients with FM. A total of 45 patients completed this open-label, randomized, nonplacebo-controlled clinical study. The numerical rating scale scores in the FMT group were slightly lower than the control group at 1 month (P > .05), and they decreased significantly at 2, 3, 6, and 12 months after treatment (P < .001). Besides, compared with the control group, the Widespread Pain Index, Symptom Severity, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index scores were significantly lower in the FMT group at different time points (P < .001). After 6 months of treatment, there was a significant increase in serotonin (5-hydroxytryptamine) and gamma-aminobutyric acid levels (P < .001), while glutamate levels significantly decreased in the FMT group (P < .001). The total effective rate was higher in the FMT group (90.9%) compared to the control group (56.5%) after 6 months of treatment (P < .05). FMT can effectively improve the clinical symptoms of FM. With the close relations between the changes in neurotransmitters and FM, certain neurotransmitters may serve as a diagnostic marker or potential target for FM patients. PERSPECTIVE: FMT is a novel therapy that aims to restore the gut microbial balance and modulate the gut-brain axis. It is valuable to further explore the therapeutic effect of FMT on FM. Furthermore, certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.

Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome characterized by widespread pain and a variety of other symptoms, including fatigue, cognitive dysfunction, and sleep disturbances. Recent research has highlighted the potential role of pro-inflammatory cytokines and neurotransmitters in the pathophysiology of FM. This study aimed to investigate the relationship between serum levels of interleukin-6 (IL-6) and serotonin with the clinical parameters observed in patients with fibromyalgia. Additionally, it sought to analyze the similarities and differences among the different groups classified by symptom severity.

This cross-sectional study included 26 female patients aged 20-70 diagnosed with FM according to the American College of Rheumatology (ACR) 2016 criteria and 14 healthy controls (HCs). Serum levels of IL-6 and serotonin were measured using electrochemiluminescence and high-performance liquid chromatography (HPLC), respectively.

FM patients exhibited significantly higher pain scores (VAS), anxiety, and depression levels compared to HCs. FIQ-R scores were significantly elevated in FM patients, with stratification showing 3.8% mild, 65.4% moderate, 23.1% severe, and 7.7% very severe cases. While no significant difference in IL-6 levels was observed between the FM patients and HCs, a trend towards increased IL-6 levels in patients with higher FIQ-R scores was noted. Serum serotonin levels were significantly lower in the FM patients than in the HCs, with moderate patients having lower levels than those classified as severe and very severe.

The study underscores the potential role of IL-6 and serotonin in the pathophysiology of FM, suggesting that these biomarkers could be relevant in assessing the severity and impact of FM. Further research is needed to elucidate these relationships and their implications for developing personalized treatment strategies.

Patient education is a core component of treating fibromyalgia and central sensitization disorders. We sought to evaluate whether patients with fibromyalgia prefer virtual or in-person educational classes as part of their treatment program, identify underlying factors with their educational modality choice, and highlight benefits or barriers associated with in-person or online educational sessions.

A cross-sectional survey with a qualitative feedback component was utilized.

A voluntary, anonymous survey was distributed to all participants (in-person and virtual) of the fibromyalgia and chronic fatigue clinic treatment program from October 2021 through March 2022.

In total 90 participants completed the survey. Nearly all (94%) agreed that the pathophysiologic education was relevant and valuable and (98%) agreed to feeling confident with implementing management strategies. Perceived connection between the participants varied between groups (85% of in-person vs 48% of online; p < .001), as did perceived engagement (100% of in-person vs 71% of online; p = .001).

Patients value education and find it useful in treating fibromyalgia, regardless of the educational modality. The online group reported more limitations including less engagement, class participation, and connection with peers.

As virtual education platforms become more widely available and may be easier to access than in-person options, it is important to understand patient preferences, benefits, and disadvantages of educational modalities to ensure education and patient outcomes remain equitable.

Long COVID should be limited to patients with multiple, persistent symptoms not related to well-defined organ damage. Once redefined, a focused review of long COVID demonstrates striking similarity to chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), fibromyalgia (FM) and irritable bowel syndrome (IBS). Research in long COVID has revealed similar findings to those noted in CFS/ME and FM, characterized by central nervous system organ dysfunction. Long COVID, like CFS/ME, FM and IBS, is best understood as a bidirectional mind-body, neuroimmune illness.

Background: Fibromyalgia is a chronic disorder marked by widespread muscle and joint pain, persistent fatigue, sleep disturbances, and irregularities in the autonomic nervous system (ANS). Methods: This study compared the effectiveness of neuromodulation using the EXOPULSE Mollii suit with a structured exercise program in regulating ANS function in fibromyalgia patients. In this randomized, longitudinal crossover study, 10 female patients were randomly assigned to either the Suit + Exercise group or the Exercise + Suit group. Each group participated in two sessions per week for eight weeks, followed by a two-week washout period before switching to the other intervention. We measured cortical arousal, microcirculation, and heart rate variability (HRV) before and after the 1st, 8th, and 16th sessions. Results: The results showed significant improvements in cortical arousal, HRV, and microcirculation with the neuromodulation treatment whereas the exercise program only produced short-term improvements in cortical arousal. Conclusion: The EXOPULSE Mollii suit exhibited cumulative benefits on ANS modulation over time, suggesting potential long-term advantages for managing fibromyalgia. However, further research is needed to explore the delayed effects of both treatments on ANS modulation.