Neutrophils infiltrate sensory ganglia and mediate chronic widespread pain in fibromyalgia.

Fibromyalgia is a debilitating widespread chronic pain syndrome that occurs in 2 to 4% of the population. The prevailing view that fibromyalgia results from central nervous system dysfunction has recently been challenged with data showing changes in peripheral nervous system activity. Using a mouse model of chronic widespread pain through hyperalgesic priming of muscle, we show that neutrophils invade sensory ganglia and confer mechanical hypersensitivity on recipient mice, while adoptive transfer of immunoglobulin, serum, lymphocytes, or monocytes has no effect on pain behavior. Neutrophil depletion abolishes the establishment of chronic widespread pain in mice. Neutrophils from patients with fibromyalgia also confer pain on mice. A link between neutrophil-derived mediators and peripheral nerve sensitization is already established. Our observations suggest approaches for targeting fibromyalgia pain via mechanisms that cause altered neutrophil activity and interactions with sensory neurons.

Self-guided digital behavioural therapy versus active control for fibromyalgia (PROSPER-FM): a phase 3, multicentre, randomised controlled trial.

BACKGROUND: International guidelines have recommended cognitive behavioural therapy, including acceptance and commitment therapy (ACT), as it offers validated benefits for managing fibromyalgia; however, it is inaccessible to most patients. We aimed to evaluate the effect of a 12-week, self-guided, smartphone-delivered digital ACT programme on fibromyalgia management. METHODS: In the PROSPER-FM randomised clinical trial conducted at 25 US community sites, adult participants aged 22-75 years with fibromyalgia were recruited and randomly assigned (1:1) to the digital ACT group or an active control group that offered daily symptom tracking and monitoring and access to health-related and fibromyalgia-related educational materials. Randomisation was done with a web-based system in permuted blocks of four at the site level. We used a blind-to-hypothesis approach in which participants were informed they would be randomly assigned to one of two potentially effective therapies under evaluation. Research staff were not masked to group allocation, with the exception of a masked statistics group while preparing statistical programming for the interim analysis. The primary endpoint was patient global impression of change (PGIC) response rate at week 12. Analyses were by intention to treat. The trial was registered with ClinicalTrials.gov, NCT05243511 (now fully closed). FINDINGS: Between Feb 8, 2022, and Feb 2, 2023, 590 individuals were screened, of whom 275 (257 women and 18 men) were randomly assigned to the digital ACT group (n=140) and the active control group (n=135). At 12 weeks, 99 (71%) of 140 ACT participants reported improvement on PGIC versus 30 (22%) of 135 active control participants, corresponding to a difference in proportions of 48·4% (95% CI 37·9-58·9; p<0·0001). No device-related safety events were reported. INTERPRETATION: Digital ACT was safe and efficacious compared with digital symptom tracking in managing fibromyalgia in adult patients. FUNDING: Swing Therapeutics.

Identifying the genetic association between the cerebral cortex and fibromyalgia.

Fibromyalgia (FM) is a central sensitization syndrome that is strongly associated with the cerebral cortex. This study used bidirectional two-sample Mendelian randomization (MR) analysis to investigate the bidirectional causality between FM and the cortical surface area and cortical thickness of 34 brain regions. Inverse variance weighted (IVW) was used as the primary method for this study, and sensitivity analyses further supported the results. The forward MR analysis revealed that genetically determined thinner cortical thickness in the parstriangularis (OR = 0.0567 mm, PIVW = 0.0463), caudal middle frontal (OR = 0.0346 mm, PIVW = 0.0433), and rostral middle frontal (OR = 0.0285 mm, PIVW = 0.0463) was associated with FM. Additionally, a reduced genetically determined cortical surface area in the pericalcarine (OR = 0.9988 mm2, PIVW = 0.0085) was associated with an increased risk of FM. Conversely, reverse MR indicated that FM was associated with cortical thickness in the caudal middle frontal region (ß = -0.0035 mm, PIVW = 0.0265), fusiform region (ß = 0.0024 mm, SE = 0.0012, PIVW = 0.0440), the cortical surface area in the supramarginal (ß = -9.3938 mm2, PIVW = 0.0132), and postcentral regions (ß = -6.3137 mm2, PIVW = 0.0360). Reduced cortical thickness in the caudal middle frontal gyrus is shown to have a significant relationship with FM prevalence in a bidirectional causal analysis.

Rheumatology: What You May Have Missed in 2023.

Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published in 2023 that offer valuable insights for internal medicine specialists and subspecialists outside of rheumatology. The first study investigated the effect of low-dose glucocorticoids on patients with rheumatoid arthritis (RA) over 2 years and challenged existing perceptions about the risks of glucocorticoids in this setting. The second study focused on the updated guideline for preventing and treating glucocorticoid-induced osteoporosis. With the chronic and widespread use of glucocorticoids, the American College of Rheumatology emphasized the importance of assessing fracture risk and initiating pharmacologic therapy when appropriate. The third study explored the potential use of methotrexate in treating inflammatory hand osteoarthritis, suggesting a novel approach to managing this challenging and common condition. The results of the fourth article we highlight suggest that sarilumab has promise as an adjunct treatment of polymyalgia rheumatica relapse during glucocorticoid dosage tapering. The fifth study evaluated sublingual cyclobenzaprine for fibromyalgia treatment, noting both potential benefits and risks. Finally, the sixth article is a systematic review and meta-analysis that assessed the therapeutic equivalence of biosimilars and reference biologics in the treatment of patients with RA. Knowledge of this recent literature will be useful to clinicians regardless of specialty who care for patients with these commonly encountered conditions.

Role of ERK in gender difference of fibromyalgia pain.

This study investigated the ERK pathway of the peripheral nervous system and discovered a gender-specific pattern of ERK activation in the dorsal root ganglion of an acid-induced chronic widespread muscular pain model. We employed a twice acid-induced chronic musculoskeletal pain model in rats to evaluate mechanical pain behavior in both male and female groups. We further conducted protein analysis of dissected dorsal root ganglions from both genders. Both male and female rats exhibited a similar pain behavior trend, with females demonstrating a lower pain threshold. Protein analysis of the dorsal root ganglion (DRG) showed a significant increase in phosphorylated ERK after the second acid injection in all groups. However, phosphorylation of ERK was observed in the dorsal root ganglion, with higher levels in the male ipsilateral group compared to the female group. Moreover, there was a no difference between the left and right sides in males, whereas the significant difference was observed in females. In conclusions, the administration of acid injections induced painful behavior in rats, and concurrent with this, a significant upregulation of pERK was observed in the dorsal root ganglia, with a greater magnitude of increase in males than females, and in the contralateral side compared to the ipsilateral side. Our findings shed light on the peripheral mechanisms underlying chronic pain disorders and offer potential avenues for therapeutic intervention.

Repeated cold stress, an animal model for fibromyalgia, elicits proprioceptor-induced chronic pain with microglial activation in mice.

BACKGROUND: Fibromyalgia is characterized by chronic pain, fatigue, and other somatic symptoms. We have recently revealed that proprioceptor hyperactivation induces chronic pain in a rat model of myalgic encephalomyelitis. The present study explores whether similar proprioceptor-induced pain is elicited in a mouse model of fibromyalgia. METHODS: Repeated cold stress (RCS) was used as a fibromyalgia model. Pain behavior was examined using the von Frey test, and neuronal activation was examined immunohistochemically as activating transcription factor (ATF)3 expression. The Atf3:BAC transgenic mouse, in which mitochondria in hyperactivated neurons are specifically labeled by green fluorescent protein, was used to trace the activated neuronal circuit. PLX3397 (pexidartinib) was used for microglial suppression. RESULTS: RCS elicited long-lasting pain in mice. ATF3, a marker of cellular hyperactivity and injury, was expressed in the lumbar dorsal root ganglion (DRG) 2 days after RCS initiation; the majority of ATF3-expressing DRG neurons were tropomyosin receptor kinase C- and/or vesicular glutamate transporter 1-positive proprioceptors. Microglial activation and increased numbers of microglia were observed in the medial part of the nucleus proprius 5 days after RCS initiation, and in the dorsal region of the ventral horn 7 days after RCS. In the ventral horn, only a subset of motor neurons was positive for ATF3; these neurons were surrounded by activated microglia. A retrograde tracer study revealed that ATF3-positive motor neurons projected to the intrinsic muscles of the foot (IMF). Using Atf3:BAC transgenic mice, we traced hyperactivated neuronal circuits along the reflex arc. Green fluorescent protein labeling was observed in proprioceptive DRG neurons and their processes originating from the IMF, as well as in motor neurons projecting to the IMF. Microglial activation was observed along this reflex arc, and PLX3397-induced microglial ablation significantly suppressed pain behavior. CONCLUSION: Proprioceptor hyperactivation leads to local microglial activation along the reflex arc; this prolonged microglial activation may be responsible for chronic pain in the present model. Proprioceptor-induced microglial activation might be the common cause of chronic pain in both the fibromyalgia and myalgic encephalomyelitis models, although the experimental models are different.

Improving the nosology of Long COVID: it is not so simple.

Long COVID is a diagnostic label currently given to those suffering from a poorly understood state of incomplete recovery or who have development of a myriad of medically unexplained symptoms occurring in the wake of infection with SARS CoV-2 that is both poorly understood and controversial. Many of the features of one of the most common clinical endotypes of Long COVID are shared by a condition well familiar to all rheumatologists and one with a large body of epidemiologic, clinical and basic research accrued over many decades namely the syndrome of fibromyalgia. Some have recently suggested that Long COVID may merely be a new name for fibromyalgia and that this diagnosis is indeed the condition that many or most may be suffering from as a post infectious sequela. In this Viewpoint we argue that while the parallels between the clinical syndrome experienced by many of those currently labeled as Long COVID and fibromyalgia are strong we should be not too quick to rename the disorder. We further argue that relabeling Long COVID as fibromyalgia is clinically reductionistic and any such relabeling may be attended by harm in both the design and execution of a future research agenda as well to patients who may be inadvertently and unfortunately pejoritised by such labeling. We further explore the parallels and differences between Long COVID and fibromyalgia and outline areas of needed future research and care.

Rheumatology and Long COVID: lessons from the study of fibromyalgia.

Rheumatology, such as other subspecialties, has both a unique perspective to offer as well as an evolving role to play in the global COVID-19 pandemic. Our field has already contributed meaningfully to the development and repurposing of many of the immune-based therapeutics which are now standard treatments for severe forms of the disease as well as to the understanding of the epidemiology, risk factors and natural history of COVID-19 in immune-mediated inflammatory diseases. Still in evolution is our potential to contribute to burgeoning research efforts in the next phase of the pandemic: the syndrome of postacute sequelae of COVID-19 or Long COVID. While our field brings many assets to the study of Long COVID including our expertise in the investigation of chronic inflammation and autoimmunity, our Viewpoint focuses on the strong similarities between fibromyalgia (FM) and Long COVID. While one can speculate on how embracing and confident practising rheumatologists already are regarding these interrelationships, we assert that in the emerging field of Long COVID the potential lessons from the field of fibromyalgia care and research have been underappreciated and marginalised and most importantly now deserve a critical appraisal.

Long COVID: a new word for naming fibromyalgia?

Long COVID is the name given to a syndrome comprising a wide variety of symptoms persisting more than 3 months after acute benign COVID-19, with a prevalence ranging from 10 to 80%. Symptoms are very close to fibromyalgia. Several studies showed that long COVID prevalence was much higher after the first wave of the pandemics and was associated to the fact of thinking having had COVID rather than having had really COVID. Thus, it was the stress of the first wave with the lockdown and not the consequences of the infection that probably induced this high frequency of long COVID. Numbers of studies tried to find objective biological abnormalities for explaining long COVID but none of them could be replicated and convincing. The concept of long COVID seems to be a repetition of history of medicine, in which the doctors and the society gave different names to fibromyalgia with the objective of trying to highlight the fact that fibromyalgia could be a somatic disease with a well understood pathophysiology and to avoid to focus on the psychosomatic aspects of the disease. In conclusion, "to name is to soothe" as said by Roland Barthes. However, "Naming things wrongly adds to the world's unhappiness" was saying Albert Camus. Thus, the term of long COVID, which suggests viral persistence of impaired immune response to the virus, is unappropriated and should be replaced by fibromyalgia-like post-COVID syndrome. Research on the psychosomatic and somatic mechanisms involved in these fibromyalgia-like post-viral syndromes must be encouraged.

Ramosetron as an add-on therapy for refractory fibromyalgia: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study aimed to assess the efficacy and safety of intravenous ramosetron for pain relief in patients with fibromyalgia (FM) unresponsive to conventional treatments. METHODS: In this prospective, double-blind, placebo-controlled trial, 80 FM patients were randomly allocated to receive either placebo (n = 40) or ramosetron (n = 40) at a dosage of 0.3 mg/day intravenously for five consecutive days. The primary outcome was the reduction in pain intensity at the end of the treatment period, evaluated using a visual analogue scale (VAS). Secondary outcome measures included the FM Impact Questionnaire, Beck Depression Inventory (BDI), Multi-Dimensional Health Assessment Questionnaire (MDHAQ), EQ-5D and State-Trait Anxiety Inventory on days 5 (end of treatment), 7, 10 and 28. Safety was continuously monitored throughout the study. RESULTS: At the end of the treatment phase, the ramosetron group demonstrated a significantly greater reduction in VAS pain scores compared with the placebo group (1.18 ± 1.60 vs 0.54 ± 1.59, P < 0.05). Additionally, the ramosetron group exhibited significant improvements in BDI (4.42 ± 5.18 vs 1.33 ± 4.87, P < 0.05) and MDHAQ pain scale (0.37 ± 0.74 vs 0.04 ± 0.52, P < 0.05) scores. However, these improvements in pain VAS and BDI scores were not sustained through day 28. The safety profile of ramosetron was favorable, with gastrointestinal symptoms, particularly constipation, being the most commonly reported adverse events. CONCLUSIONS: Intravenous administration of ramosetron provided safe and effective short-term relief of pain intensity in FM patients with inadequate response to standard treatments.

Ameliorative effect of nano-pregabalin in gastrocnemius muscle of gamma irradiated rats with an experimental model of fibromyalgia: Crosstalk of Sirt3, IL-1ß and PARP1 pathways.

BACKGROUND: Fibromyalgia (FM) is a complex syndrome with somatic symptoms connected to the operational state of muscles. Although radiotherapy is a cornerstone in cancer treatment, it is implicated in the aggravation of FM. Lately, formulation of medicines in nano-forms become of great prominence due to their prospective applications in medicine. So, this study aimed to assess possible therapeutic benefits of formulating pregabalin in a nono-form (N-PG) for managing FM during exposure to gamma radiation. METHODS: Gamma rays administered in fractionated doses (2 Gy/day) to male rats after one hour of s.c. injection of reserpine (1 mL/kg per day) to induce FM, then treated with single daily dose of (30 mg/kg, p.o.) PG or N-PG for ten successive days. Rats were subjected to behavioral tests, then sacrificed to obtain serum and gastrocnemius muscles. RESULTS: N-PG significantly antagonized reserpine-induced FM as proved by; the immobility and performance times in forced swim and rotarod performance tests, respectively were restored near to the normal time, serum IL-8 and MCP-1 chemokines were nearby the normal levels, mitigated oxidative stress through increasing total thiol, Sirt3, CAT enzyme and decreasing COX-1, inhibition of inflammation via IL-1ß and MIF significant reduction, it possessed anti-apoptotic effect verified by decreasing PARP-1 and increasing Bcl-XL, gastrocnemius muscles had minimal fibrosis levels as seen after Masson trichrome staining. Histopathological results were coincidence with biochemical inspection. CONCLUSION: This study identifies N-PG as a novel drug that could be of a value in the management of FM particularly in cancer patients undergoing radiotherapy.

Impaired mitochondrial quality control in fibromyalgia: Mechanisms involved in skeletal muscle alteration.

Fibromyalgia (FMS) is a persistent syndrome marked by widespread musculoskeletal pain and behavioural symptoms. Given the hypothesis linking FMS aetiology to mitochondrial dysfunction and oxidative stress, we examined the biochemical correlation among these factors by studying specific proteins associated with mitochondrial homeostasis in muscle. Additionally, this study investigated the role of Boswellia serrata gum resin extract (BS), known for its various functions, including the potent induction of antioxidant enzymes, in determining protective or reparative mechanisms in the muscle cells. Sprague-Dawley rats were injected with reserpine to induce FMS. These animals exhibited moderate changes in hind limb skeletal muscles, experiencing mobility difficulties. Additionally, there were noteworthy morphological and ultrastructural alterations, along with the expression of myogenin, mitochondrial enzymes and oxidative stress markers in the gastrocnemius muscle. Interestingly, BS demonstrated a reduction in spontaneous motor activity difficulties. Moreover, BS showed a positive impact on musculoskeletal morphostructural aspects, as well as a decrease in oxidative stress and mitochondrial alterations. In particular, BS restored the mRNA expression of citrate synthase and cytochrome-c oxidase subunit II and the activity of electron transfer chain complexes. BS also influenced mitochondrial biogenesis, upregulating PGC-1α expression and the related transcription factors (Nrf1, Tfam, Nrf2, FOXO3a, SIRT3, GCLC, NQO1, SOD2 and GPx4), oxidative stress (lipid peroxidation, GSH levels and GSH-Px activity) and mitochondrial dynamics and function (Mnf2 expression and CoQ10 levels). Overall, this study underlined the key role of the mitochondrial alteration in FMS and that BS had a very high antioxidant effect in these organelles and also in the cells.

Patient-Reported Impact of Symptoms in Fibromyalgia (PRISM-FM).

OBJECTIVE: To identify the frequency and relative importance of symptoms experienced by adults with fibromyalgia (FM) and determine factors associated with a higher disease burden. METHODS: We conducted semistructured interviews with 15 participants with FM, collecting 1479 quotes regarding the symptomatic burden of FM. We then performed an international cross-sectional study involving 1085 participants with FM to determine the prevalence and relative importance (scale 0-4) of 149 symptoms representing 14 symptomatic themes. We performed subgroup analysis to determine how age, sex, disease duration, medication use, employment status, change in employment status, missing work due to FM, and ability level are related to symptomatic theme prevalence. RESULTS: The symptomatic themes with the highest prevalence in FM were pain (99.8%), muscle tenderness (99.8%), and fatigue (99.3%). The symptomatic themes that had the greatest effect on patients' lives were related to fatigue (2.88), pain (2.85), muscle tenderness (2.79), and impaired sleep and daytime sleepiness (2.70). Symptomatic theme prevalence was most strongly associated with the modified Rankin Scale level of disability, disability status, and change in employment status (on disability vs not on disability). CONCLUSION: Participants with FM identify a variety of symptoms that significantly affect their daily lives. Many of these symptoms, such as fatigue, sleep disturbance, and activity limitation, are life-altering and not related to traditional diagnostic criteria. Symptom prevalence in this population varies across subgroups based on demographic categories and disability status.

Incidence and Prevalence of Pain Medication Prescriptions in Pathologies with a Potential for Chronic Pain.

BACKGROUND: Heightened risks of dependence, addiction, anxiolytic effects, or prescription overdose death due to long-term use of pain medication have increased awareness about extended pain medication use in chronic pain populations. The goal of this study was to evaluate the incidence and prevalence of pain medication prescriptions from 2012 to 2022 in common pathologies with a potential for chronic pain. METHODS: A retrospective cohort study was conducted using electronic health records from TriNetX (Cambridge, Massachusetts) Global Collaborative Network. For 10 distinct cohorts (total n = 9,357,584 patients), pain medication prescriptions were extracted for five classes, namely nonsteroidal anti-inflammatory drug (NSAIDs) and acetaminophen, opioids, gabapentinoids, neuropathic mood agents, and muscle relaxants. Annual incidence and prevalence of each class of medication were evaluated for the past 11 yr. RESULTS: From 2012 to 2022, there was a significant increase in prescriptions of NSAIDs, except for patients with fibromyalgia, and persistent spinal pain syndrome (PSPS) type 2. Interestingly, over time, prescriptions of opioids in patients with complex regional pain syndrome, endometriosis, osteoarthritis, and PSPS type 2 increased, as did prescriptions of muscle relaxants for all cohorts except those with fibromyalgia. Incidence of prescriptions of neuropathic mood agents is high for patients with complex regional pain syndrome (both types) and PSPS type 2. Only for benzodiazepines did there seem to be a decline over the years, with a significantly decreased time trend in patients with complex regional pain syndrome type 1, fibromyalgia, and PSPS type 2. CONCLUSIONS: During the last 11 yr, an increase in incidence of NSAIDs and acetaminophen, opioids, neuropathic agents, and muscle relaxants was observed. Only prescriptions of benzodiazepines significantly decreased over time in specific cohorts. Overall, patients with PSPS type 2 and complex regional pain syndrome (both types) consume a broad variety of pain medication classes.

Phenotypic characteristics of patients with chronic widespread pain and fibromyalgia: a cross-sectional cluster analysis.

OBJECTIVE: This study aimed to explore whether phenotypic characteristics of patients with chronic widespread pain (CWP) and fibromyalgia (FM) can be aggregated into definable clusters that may help to tailor treatments. METHOD: Baseline variables (sex, age, education, marital/employment status, pain duration, prior CWP/FM diagnosis, concomitant rheumatic disease, analgesics, tender point count, and disease variables derived from standardized questionnaires) collected from 1099 patients (93.4% females, mean age 44.6 years) with a confirmed CWP or FM diagnosis were evaluated by hierarchical cluster analysis. The number of clusters was based on coefficients in the agglomeration schedule, supported by dendrograms and silhouette plots. Simple and multiple regression analyses using all variables as independent predictors were used to assess the likelihood of cluster assignment, reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Only one cluster emerged (Cluster 1: 455 patients). Participants in this cluster were characterized as working (OR 66.67, 95% CI 7.14 to 500.00), with a medium-term/higher education (OR 16.80, 95% CI 1.94 to 145.41), married/cohabiting (OR 14.29, 95% CI 1.26 to 166.67), and using mild analgesics (OR 25.64, 95% CI 0.58 to > 999.99). The odds of being an individual in Cluster 1 were lower when having a worse score on the PDQ (score ≥ 18) (OR < 0.001, 95% CI < 0.001 to 0.02). CONCLUSION: We identified one cluster, where participants were characterized by a potentially favourable clinical profile. More studies are needed to evaluate whether these characteristics could be used to guide the management of patients with CWP and FM.

Long-term stress exposure, cortisol level and cardiovascular activity and reactivity: Observations in patients with fibromyalgia.

Previous research suggested that exposure to long-lasting or repeated laboratory stressors may lead to rearrangement of cardiovascular control, with a shift of regulation mechanisms from dominant cardiac to dominant vascular influences between the early and late response phases, respectively. This study investigated whether similar rearrangement occurs during life stress accompanying chronic disease by analyzing also associations between cortisol level and cardiovascular variables in patients with fibromyalgia (FM). In 47 women with FM and 36 healthy women (HW), cardiovascular recordings were taken during active body posture changes (sitting, lying down, and standing). Moreover, hair cortisol concentration (HCC) was obtained. During standing, which involved orthostatic challenge, FM patients showed higher total peripheral resistance (TPR) but lower stroke volume (SV), cardiac output (CO), and baroreflex sensitivity than HW. During sitting and lying down, TPR was more closely associated with blood pressure (BP) than CO in FM patients; in contrast, CO was more closely associated with BP than TPR in HW. HCC correlated positively with TPR and BP in FM patients, but negatively with TPR and BP and positively with SV and CO in HW. Results suggest that chronic disease-related stress is associated with alterations in cardiovascular regulation toward greater involvement of vascular than cardiac mechanisms in BP control. Stress-related cortisol release may contribute to the long-term rearrangement of autonomic regulation. At the behavioral level, the dominance of vascular over cardiovascular control may relate to reduced somatic mobilization during an active fight-flight response in favor of passive and behaviorally immobile coping.

Tailored exercise programmes for fibromyalgia: a clinical practical guide.

OBJECTIVES: To evaluate the role of exercise in the management of fibromyalgia syndrome (FM) by addressing its complex pathogenesis involving central sensitisation, autonomic dysfunction, inflammation, and neurological irregularities, and examining how exercise impacts symptom exacerbation caused by external stressors and comorbid conditions. METHODS: This review synthesises evidence from current literature focusing on the benefits of structured and personalised exercise programmes in FM management. It discusses the importance of specifying exercise type, intensity, frequency, duration, and progression tailored to individual patient needs and clinical objectives. RESULTS: Regular physical activity effectively mitigates core aetiopathogenetic mechanisms of FM and improves associated conditions such as stress and obesity. It also provides benefits for preventing other chronic diseases, enhancing well-being, and promoting healthy ageing. Structured and personalised exercise programmes that start with a low-demand protocol and gradually increase exercise volume are most beneficial, by improving patient compliance and reducing the risk of adverse effects. CONCLUSIONS: Effective management of FM requires a patient-centred approach integrating both pharmacological and non-pharmacological treatments, with exercise playing a pivotal role. Personalised exercise prescriptions that consider FM patients' specific needs and limitations are crucial for optimising treatment outcomes and enhancing quality of life.

Efficacy of physiotherapy treatment in medium and long term in adults with fibromyalgia: an umbrella of systematic reviews.

OBJECTIVES: To summarise the available evidence and assess the effectiveness of medium and long-term physiotherapy treatment in adults with fibromyalgia (FM). METHODS: This systematic review was registered in PROSPERO: CRD42023388356. The databases searched were MEDLINE, PEDro, Scopus, Cinhal, LatinIndex, and Cochrane, using the following keywords: "fibromyalgia", "physiotherapy", "treatment", "therapeutic exercise", "TENS", "laser therapy" and "manual therapy." The included articles analysed treatments with active or passive physiotherapy approaches in patients with FM. The variables included structural characteristics, such as: author, publication year, research question, and main outcome variables. The data on the findings of the articles comprised the following aspects: number of participants, intervention, follow-up, results, and principal conclusions. RESULTS: Thirty-three articles were analysed, with an overall PRISMA score of 18.63±3.36. The active treatment methods analysed were: movement and body awareness therapies (stretching, tai chi, yoga and Pilates); hydrotherapy; physical or aerobic exercise; and multidisciplinary therapy. The passive therapies analysed were: manual therapy; repetitive transcranial magnetic stimulation (rTMS); and other therapies (hyperbaric oxygen therapy, vibration therapy, virtual reality, transcutaneous electric nervous stimulation (TENS), pain neuroscience education, and acupuncture). Evidence was found on the positive effect of physiotherapy treatment on the signs and symptoms of fibromyalgia, such as pain, impairment of physical capacity and worse quality of life. CONCLUSIONS: The effectiveness of the active and passive therapies analysed in the management of the symptoms and signs of the disease was positive in most of the studies. However, more specific descriptions of the treatment protocol, frequency, intensity and treatment dose are required to reach a consensus, as well as primary studies for a more extended follow-up period to better evaluate long-term effects.

Environmental factors and fibromyalgia syndrome: a narrative review.

This in-depth review of fibromyalgia (FM), which is a complex condition characterised by chronic pain, fatigue, sleep disturbances, and a spectrum of diagnostically and therapeutically challenging symptoms, underlines the need for a comprehensive and integrated approach that also takes into account the psychological factors affecting patient responses. We focus on the substantial impact that environmental factors (climatic variations, air pollution, electromagnetic field exposure, physical and emotional traumas, dietary patterns, and infections) have on the manifestation and intensity of symptoms, and advocate personalised, holistic treatment of patients' psychological and environmental sensitivities by suggesting the benefits of tailored dietary and stress management. We also call for further research into the complex interplay of environmental, biological and psychological factors influencing FM in order to develop more effective individualised treatments that are capable of enhancing patient care and outcomes.