Tag: fibromyalgia

Patient and clinician experiences of fibromyalgia, ME/CFS and medically unexplained symptoms: A meta-aggregative systematic review

Abstract:

Objectives: Fibromyalgia (FM), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and other syndromes with medically unexplained symptoms (MUS) pose significant healthcare challenges. We aimed to synthesize qualitative evidence regarding the experiences of persons with these conditions (PwC) and their healthcare professionals (HCPs).

Methods & Measures: Databases were searched using terms relating to FM/ME/CFS/MUS, Experience and Qualitative research. Studies published between 2001-2021 concerning adult PwC or HCP perspectives were included and synthesized using Meta-Aggregation, with confidence established following the ConQual approach.

Results: 143 studies were included, with 708 findings aggregated into 82 categories and 13 synthesized findings. PwC narratives reflected a range of themes concerning: The experience of symptoms; The patient journey; Identity loss and change; Managing chronic illness; Understanding and legitimacy; Support needs and experiences; Healthcare needs and experiences; and Managing the healthcare encounters. HCPs perspective themes included: Beliefs and attitudes towards patients; Sensemaking at the limits of medical knowledge; Consultation and management; The patient-clinician relationship; and Barriers and facilitators to care.

Conclusion: Sensemaking challenges are at the core of the patient and clinician experience of MUS, FM and ME/CFS. While gaps in biomedical knowledge are clear, this review highlights the need to address the patient-clinician dynamic in the context of uncertainty.

Source: Duda N, Maguire R, Gitonga I, Corrigan S. Patient and clinician experiences of fibromyalgia, ME/CFS and medically unexplained symptoms: A meta-aggregative systematic review. PsyArXiv [Preprint], 28 Apr 2023  https://psyarxiv.com/5ct4k/ (Full text)

Neutrophils infiltrate sensory ganglia and mediate chronic widespread pain in fibromyalgia

Abstract:

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.

Source: Caxaria S, Bharde S, Fuller AM, Evans R, Thomas B, Celik P, Dell’Accio F, Yona S, Gilroy D, Voisin MB, Wood JN, Sikandar S. Neutrophils infiltrate sensory ganglia and mediate chronic widespread pain in fibromyalgia. Proc Natl Acad Sci U S A. 2023 Apr 25;120(17):e2211631120. doi: 10.1073/pnas.2211631120. Epub 2023 Apr 18. PMID: 37071676. https://www.pnas.org/doi/10.1073/pnas.2211631120 (Full text)

Efficacy of Low-Dose Naltrexone and Predictors of Treatment Success or Discontinuation in Fibromyalgia and Other Chronic Pain Conditions: A Fourteen-Year, Enterprise-Wide Retrospective Analysis

Abstract:

Current pharmacologic treatments may provide limited analgesia in fibromyalgia and other chronic pain disorders. Low-dose naltrexone (LDN) has emerged as a potential analgesic option that has been minimally explored.

This study aims to describe current real-world prescribing practices of LDN, to investigate if patients have a perceived benefit of LDN in treating pain symptoms and to identify predictors associated with a perceived benefit or discontinuation of LDN.

We evaluated all outpatient prescriptions for LDN prescribed for any pain indication in the Mayo Clinic Enterprise from 1 January 2009 to 10 September 2022. A total of 115 patients were included in the final analysis.

The patients were 86% female, had a mean age of 48 ± 16 years, and 61% of prescriptions were for fibromyalgia-related pain. The final daily dose of oral LDN ranged from 0.8 to 9.0 mg, while the most common dose was 4.5 mg once daily.

Of patients who reported follow-up data, 65% reported benefit in their pain symptoms while taking LDN. Adverse effects were reported in 11 (11%) patients and 36% discontinued taking LDN by the most recent follow-up.

Concomitant analgesic medications were used by 60% of patients and were not associated with perceived benefit nor discontinuation of LDN, including concomitant opioids.

LDN is a relatively safe pharmacologic option that may benefit patients with chronic pain conditions and warrants further investigation in a prospective, controlled, and well-powered randomized clinical trial.

Source: Driver CN, D’Souza RS. Efficacy of Low-Dose Naltrexone and Predictors of Treatment Success or Discontinuation in Fibromyalgia and Other Chronic Pain Conditions: A Fourteen-Year, Enterprise-Wide Retrospective Analysis. Biomedicines. 2023; 11(4):1087. https://doi.org/10.3390/biomedicines11041087 https://www.mdpi.com/2227-9059/11/4/1087 (Full text)

Synbiotic Supplementation Improves Quality of Life and Inmunoneuroendocrine Response in Patients with Fibromyalgia: Influence of Codiagnosis with Chronic Fatigue Syndrome

Abstract:

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are two medical conditions in which pain, fatigue, immune/inflammatory dysregulation, as well as various mental health disorders predominate in the diagnosis, without evidence of a clear consensus on the treatment of FM and CFS.
The main aim of this research was to analyse the possible effects of a synbiotic (Synbiotic, Gasteel Plus® (Heel España S.A.U.), through the study of pro-inflammatory/anti-inflammatory cytokines (IL-8/IL-10) and neuroendocrine biomarkers (cortisol and DHEA), in order to evaluate the interaction between inflammatory and stress responses mediated by the cytokine-HPA (hypothalamic-pituitary-adrenal) axis, as well as mental and physical health using body composition analysis, accelerometry and previously validated questionnaires.
The participants were women diagnosed with FM with or without a diagnostic of CFS. Each participant was evaluated at baseline and after the intervention, which lasted one month. Synbiotic intervention decreased levels of perceived stress, anxiety and depression, as well as improved quality of life during daily activities. In addition, the synbiotic generated an activation of HPA axis (physiological cortisol release) that can compensate the increased inflammatory status (elevated IL-8) observed at baseline in FM patients. There were no detrimental changes in body composition or sleep parameters, as well as in the most of the activity/sedentarism-related parameters studied by accelerometry.
It is concluded that synbiotic nutritional supplements can improve the dysregulated immunoneuroendocrine interaction involving inflammatory and stress responses in women diagnosed with FM, particularly in those without a previous CFS diagnostic; as well as their perceived of levels stress, anxiety, depression and quality of life.
Source: Hinchado MD, Quero-Calero CD, Otero E, Gálvez I, Ortega E. Synbiotic Supplementation Improves Quality of Life and Inmunoneuroendocrine Response in Patients with Fibromyalgia: Influence of Codiagnosis with Chronic Fatigue Syndrome. Nutrients. 2023; 15(7):1591. https://doi.org/10.3390/nu15071591 https://www.mdpi.com/2072-6643/15/7/1591 (Full text)

Heart Rate Variability and Salivary Biomarkers Differences between Fibromyalgia and Healthy Participants after an Exercise Fatigue Protocol: An Experimental Study

Abstract:

Previous studies showed that people with Fibromyalgia (FM) suffer from dysautonomia. Dysautonomia consists of persistent autonomic nervous system hyperactivity at rest and hyporeactivity during stressful situations. There is evidence that parameters reflecting the complex interplay between the autonomic nervous system and the cardiovascular system during exercise can provide significant prognostic information. Therefore, this study aimed to investigate the differences between people with FM and healthy controls on heart rate variability (HRV) and salivary parameters (such as flow, protein concentration, enzymatic activities of amylase, catalase and glutathione peroxidase) in two moments: (1) at baseline, and (2) after an exercise fatigue protocol.

A total of 37 participants, twenty-one were people with fibromyalgia and sixteen were healthy controls, participated in this cross-sectional study. HRV and salivary samples were collected before and after an exercise fatigue protocol. The fatigue protocol consisted of 20 repetitions of knee extensions and flexions of the dominant leg at 180 °·s-1 (degrees per second).

Significant differences were found in the HRV (stress index, LF and HF variables) and salivary biomarkers (with a higher concentration of salivary amylase in people with FM compared to healthy controls). Exercise acute effects on HRV showed that people with FM did not significantly react to exercise. However, significant differences between baseline and post-exercise on HRV significantly induce alteration on the HRV of healthy controls. Catalase significantly increased after exercise in healthy controls whereas salivary flow significantly increased in women with FM after an exercise fatigue protocol.

Our study suggests that a higher α-amylase activity and an impaired HRV can be used as possible biomarkers of fibromyalgia, associated with a reduction in salivary flow without changes in HRV and catalase activity after a fatigue exercise protocol. More studies should be carried out in the future to evaluate this hypothesis, in order to find diagnostic biomarkers in fibromyalgia.

Source: Costa AR, Freire A, Parraca JA, Silva V, Tomas-Carus P, Villafaina S. Heart Rate Variability and Salivary Biomarkers Differences between Fibromyalgia and Healthy Participants after an Exercise Fatigue Protocol: An Experimental Study. Diagnostics (Basel). 2022 Sep 14;12(9):2220. doi: 10.3390/diagnostics12092220. PMID: 36140620; PMCID: PMC9497903. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497903/ (Full text)

The Behavior of Muscle Oxygen Saturation, Oxy and Deoxy Hemoglobin during a Fatigue Test in Fibromyalgia

Abstract:

Previous studies have reported that people with fibromyalgia (FM) could suffer from mitochondrial dysfunction. However, the consumption of muscle oxygen during physical exercise has been poorly studied. Therefore, this study aimed to explore the response of muscle oxygen during a fatigue protocol in people with FM and healthy controls (HC). In addition, the peak torque and the total work were assessed.

A total of 31 participants (eighteen were people with fibromyalgia and thirteen were healthy controls) were enrolled in this cross-sectional study. All the participants underwent a fatigue protocol consisting of 20 repetitions at 180°·s−1 of quadriceps flexions and extensions using a Biodex System 3. The muscle oxygen saturation (SmO2), total hemoglobin (THb), deoxygenated hemoglobin (HHb) and oxygenated hemoglobin (O2Hb) values were measured using a portable near-infrared spectroscopy (NIRS) device. Significant differences between people with FM and healthy controls were found at baseline: SmO2 (FM: 56.03 ± 21.36; HC: 77.41 ± 10.82; p = 0.036), O2Hb (FM: 6.69 ± 2.59; HC: 9.37 ± 1.31; p = 0.030) and HHb (FM: 5.20 ± 2.51; HC: 2.73 ± 1.32; p = 0.039); during the fatigue protocol: SmO2 (FM: 48.54 ± 19.96; HC: 58.87 ± 19.72; p = 0.038), O2Hb (FM: 5.70 ± 2.34; HC: 7.06 ± 2.09; p = 0.027) and HHb (FM: 5.69 ± 2.65; HC: 4.81 ± 2.39; p = 0.048); and in the recovery at three min and six min for SmO2, O2Hb and HHb (p < 0.005).

Furthermore, healthy control values of SmO2, O2Hb and HHb have been significantly altered by the fatigue protocol (p < 0.005). In contrast, people with FM did not show any significant alteration in these values. Moreover, significant differences were found in the peak torque at extension (FM: 62.48 ± 24.45; HC: 88.31 ± 23.51; p = 0.033) and flexion (FM: 24.16 ± 11.58; HC: 42.05 ± 9.85; p = 0.010), and the total work performed at leg extension (FM: 1039.78 ± 434.51; HC: 1535.61 ± 474.22; p = 0.007) and flexion (FM: 423.79 ± 239.89; HC: 797.16 ± 194.37; p = 0.005).

Source: Villafaina S, Tomas-Carus P, Silva V, Costa AR, Fernandes O, Parraca JA. The Behavior of Muscle Oxygen Saturation, Oxy and Deoxy Hemoglobin during a Fatigue Test in Fibromyalgia. Biomedicines. 2023 Jan 4;11(1):132. doi: 10.3390/biomedicines11010132. PMID: 36672640; PMCID: PMC9856161. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856161/ (Full text)

Is Central Sensitisation the Missing Link of Persisting Symptoms after COVID-19 Infection?

Abstract:

Patients recovered from a COVID-19 infection often report vague symptoms of fatigue or dyspnoea, comparable to the manifestations in patients with central sensitisation. The hypothesis was that central sensitisation could be the underlying common aetiology in both patient populations. This study explored the presence of symptoms of central sensitisation, and the association with functional status and health-related quality of life, in patients post COVID-19 infection.

Patients who were previously infected with COVID-19 filled out the Central Sensitisation Inventory (CSI), the Post-COVID-19 Functional Status (PCFS) Scale and the EuroQol with five dimensions, through an online survey. Eventually, 567 persons completed the survey. In total, 29.73% of the persons had a score of <40/100 on the CSI and 70.26% had a score of ≥40/100. Regarding functional status, 7.34% had no functional limitations, 9.13% had negligible functional limitations, 37.30% reported slight functional limitations, 42.86% indicated moderate functional limitations and 3.37% reported severe functional limitations.

Based on a one-way ANOVA test, there was a significant effect of PCFS Scale group level on the total CSI score (F(4,486) = 46.17, p < 0.001). This survey indicated the presence of symptoms of central sensitisation in more than 70% of patients post COVID-19 infection, suggesting towards the need for patient education and multimodal rehabilitation, to target nociplastic pain.

Source: Goudman L, De Smedt A, Noppen M, Moens M. Is Central Sensitisation the Missing Link of Persisting Symptoms after COVID-19 Infection? J Clin Med. 2021 Nov 28;10(23):5594. doi: 10.3390/jcm10235594. PMID: 34884296; PMCID: PMC8658135. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658135/ (Full text)

Could the fibromyalgia syndrome be triggered or enhanced by COVID-19?

Abstract:

Fibromyalgia (FM) is a complex disease with an uncertain aetiology and intricate pathophysiology. Although its genesis is not fully explained, potential environmental factors, such as viral infections might trigger FM or worsen patients’ clinical outcomes.

The SARS-CoV-2 virus may affect central and peripheral nervous systems, leading to musculoskeletal, neurological, and psychological disturbances. These symptoms might persist at least 12 months beyond the recovery, often referred to as post-COVID syndrome, which resembles FM syndrome. In this sense, we argued the potential consequences of COVID-19 exclusively on FM syndrome.

First, we have described post-COVID syndrome and its painful symptoms. Afterwards, we argued whether FM syndrome could be triggered or enhanced by COVID-19 infection or by numerous and persistent stressors imposed daily by the pandemic setting (isolation, uncertainty, depression, mental stress, generalized anxiety, and fear of the virus). In addition, we have demonstrated similarities between pathophysiological mechanisms and cardinal symptoms of FM and COVID-19, speculating that SARS-CoV-2 might represent a critical mediator of FM or an exacerbator of its symptoms once both syndromes share similar mechanisms and complaints.

Therefore, pharmacologic and non-pharmacological approaches commonly used to treat FM could serve as strategic therapies to attenuate painful and neurological manifestations of post-COVID syndrome. Although it is still theoretical, clinicians and researchers should be alert of patients who develop symptoms similar to FM or those who had their FM symptoms increased post-COVID to manage them better.

Source: Fialho MFP, Brum ES, Oliveira SM. Could the fibromyalgia syndrome be triggered or enhanced by COVID-19? Inflammopharmacology. 2023 Feb 27:1–19. doi: 10.1007/s10787-023-01160-w. Epub ahead of print. PMID: 36849853; PMCID: PMC9970139. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970139/ (Full text)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia: PR3-versus MPO-ANCA-associated vasculitis, an exploratory cross-sectional study

Summary:

Background: Persistent fatigue is a common complaint in ANCA-vasculitis (AAV) patients and has a profound impact on patient’s quality of life. The symptoms associated with this fatigue mirror those found in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia. Etiologic and pathophysiologic differences exist between PR3- and MPO-ANCA disease, yet differences in their fatigue manifestations have not been well researched. We compared fatigue and its associations in healthy controls, AAV patients and fibromyalgia controls.

Methods: The Canadian consensus criteria were used for ME/CFS diagnosis, and American College of Rheumatology criteria for fibromyalgia diagnosis. Factors such as cognitive failure, depression, anxiety, and sleep disturbances were assessed by patient reported questionnaires. Clinical factors such as BVAS, vasculitis damage index, CRP and BMI were also collected.

Findings: Our AAV cohort comprised 52 patients, with a mean age of 44.7 (20–79), 57% (30/52) of the patients were female. We found 51.9% (27/52) of patients fulfilled the diagnostic criteria for ME/CFS, with 37% (10/27) of those having comorbid fibromyalgia. Rates of fatigue were higher in MPO-ANCA patients, than in PR3-ANCA patients, and their symptoms were more similar to the fibromyalgia controls. Fatigue in PR3-ANCA patients was related to inflammatory markers. These differences may be due to the varied pathophysiology of the PR3- and MPO-ANCA serotypes.

Interpretation: A large proportion of AAV patients suffer from debilitating fatigue consequential enough to meet the diagnostic criteria for ME/CFS. Fatigue associations were not the same between PR3- and MPO-ANCA patients, suggesting that the underlying mechanisms may be different. Future studies should consider ANCA serotype, as further research may inform different clinical treatment strategies for AAV patients suffering from ME/CFS.

Source: Charmaine van Eeden, Naima Mohazab, Desiree Redmond, Elaine Yacyshyn, Alison Clifford, Anthony S. Russell, Mohammed S. Osman, and Jan Willem Cohen Tervaer. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia: PR3-versus MPO-ANCA-associated vasculitis, an exploratory cross-sectional study. The Lancet Regional Health – Americas 2023;20: 100460.  https://www.thelancet.com/journals/lanam/article/PIIS2667-193X(23)00034-0/fulltext# (Full text)

The Link Between Empty Sella Syndrome, Fibromyalgia, and Chronic Fatigue Syndrome: The Role of Increased Cerebrospinal Fluid Pressure

Abstract:

The etiopathogenesis of fibromyalgia (FM) and chronic fatigue syndrome (CFS) is not yet elucidated. Hypothalamo-pituitary-adrenal (HPA) axis dysfunction is reflected in the hormonal disturbances found in FM and CFS. Some study groups have introduced a novel hypothesis that moderate or intermittent intracranial hypertension may be involved in the etiopathogenesis of FM and CFS.

In these conditions, hormonal disturbances may be caused by the mechanical effect of increased cerebrospinal fluid pressure, which hampers blood flow in the pituitary gland. Severe intracranial pressure may compress the pituitary gland, resulting in primary empty sella (ES), potentially leading to pituitary hormone deficiencies.

The aim of this narrative review was to explore whether similar hormonal changes and symptoms exist between primary ES and FM or CFS and to link them to cerebrospinal fluid pressure dysregulation. A thorough search of the PubMed and Web of Science databases and the reference lists of the included studies revealed that several clinical characteristics were more prevalent in primary ES, FM or CFS patients than in controls, including increased cerebrospinal fluid pressure, obesity, female sex, headaches and migraine, fatigue, visual disturbances (visual acuity and eye motility abnormalities), vestibulocochlear disturbances (vertigo and neurosensorial hearing loss), and bodily pain (radicular pain and small-fiber neuropathy).

Furthermore, challenge tests of the pituitary gland showed similar abnormalities in all three conditions: blunted adrenocorticotropic hormone, cortisol, growth hormone, luteinizing hormone, and thyroid stimulating hormone responses and an increased prolactin response. The findings of this narrative review provide further support for the hypothesis that moderately or intermittently increased cerebrospinal fluid pressure is involved in the pathogenesis of FM and CFS and should stimulate further research into the etiopathogenesis of these conditions.

Source: Hulens M, Dankaerts W, Rasschaert R, Bruyninckx F, De Mulder P, Bervoets C. The Link Between Empty Sella Syndrome, Fibromyalgia, and Chronic Fatigue Syndrome: The Role of Increased Cerebrospinal Fluid Pressure. J Pain Res. 2023;16:205-219
https://doi.org/10.2147/JPR.S394321 https://www.dovepress.com/the-link-between-empty-sella-syndrome-fibromyalgia-and-chronic-fatigue-peer-reviewed-fulltext-article-JPR (Full text)