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Diagnostics
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Chronic Pain and Fibromyalgia: Biomarkers and Pathophysiology
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Chronic Pain and Fibromyalgia: Biomarkers and Pathophysiology

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 10737

Special Issue Editors

Prof. Dr. Manuela Di Franco

E-Mail Website
Guest Editor
Department of Internal Medicine and Medical Specialities, Universita degli Studi di Roma La Sapienza, 00185 Rome, Italy
Interests: early arthritis; rheumatoid arthritis; inflammatory arthritis; chronic pain; fibromyalgia
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Piercarlo Sarzi-Puttini

E-Mail Website
Co-Guest Editor
Rheumatology Unit, L. Sacco University Hospital, Milan, Italy
Interests: anti-cytokine therapy; rheumatoid arthritis

Special Issue Information

Dear Colleagues,

Fibromyalgia (FM) is one of the most disabling chronic pain syndromes, especially affecting women and middle-aged people, with a global prevalence between 0.2% and 6.6%. FM still represents a clinical enigma with real diagnostic difficulties since its pathophysiology is not well known and its symptoms are nonspecific and overlap with those of many other disorders. The American College of Rheumatology (ACR) criteria for FM diagnosis have changed over time, and clinicians rely only on clinical examination and questionnaire administration to make a diagnosis. Neither specific diagnostic laboratory tests nor biomarkers are available for confirming FM diagnosis, but it is well known that cytokines, chemokines, mu opioid positive B lymphocytes, genetic polymorphisms, substance P, nerve growth factor, brain-derived neurotrophic factor, glutamate, tryptophan, and melatonin are involved in the pathogenesis.

In this context, delays and misdiagnoses may frequently occur, with relevant consequences for patients’ lives and treatment efficacy, as well as socioeconomic burdens on patients and the healthcare system. For these reasons, the identification of objective and specific FM biomarkers is a priority for correct diagnosis. FM probably cannot be diagnosed with a single biomarker, but different factors are involved in specific subsets of the syndrome.

Prof. Dr. Manuela Di Franco
Prof. Dr. Piercarlo Sarzi-Puttini
Guest Editors

Manuscript Submission Information

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Published Papers (3 papers)

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13 pages, 544 KiB  
Article
Heart Rate Variability and Salivary Biomarkers Differences between Fibromyalgia and Healthy Participants after an Exercise Fatigue Protocol: An Experimental Study
by Ana Rodrigues Costa, Ana Freire, Jose A. Parraca, Vanda Silva, Pablo Tomas-Carus and Santos Villafaina
Diagnostics 2022, 12(9), 2220; https://doi.org/10.3390/diagnostics12092220 - 14 Sep 2022
Cited by 4 | Viewed by 2127
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Chronic Pain and Fibromyalgia: Biomarkers and Pathophysiology)
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15 pages, 3371 KiB  
Article
Network Analysis for Better Understanding the Complex Psycho-Biological Mechanisms behind Fibromyalgia Syndrome
by Juan Antonio Valera-Calero, Lars Arendt-Nielsen, Margarita Cigarán-Méndez, César Fernández-de-las-Peñas and Umut Varol
Diagnostics 2022, 12(8), 1845; https://doi.org/10.3390/diagnostics12081845 - 30 Jul 2022
Cited by 15 | Viewed by 2246
Abstract
The aim of this study was to assess potential associations between sensory, cognitive, health-related, and physical variables in women with fibromyalgia syndrome (FMS) using a network analysis for better understanding the complexity of psycho-biological mechanisms. Demographic, clinical, pressure pain threshold (PPT), health-related, physical, [...] Read more.
The aim of this study was to assess potential associations between sensory, cognitive, health-related, and physical variables in women with fibromyalgia syndrome (FMS) using a network analysis for better understanding the complexity of psycho-biological mechanisms. Demographic, clinical, pressure pain threshold (PPT), health-related, physical, and psychological/cognitive variables were collected in 126 women with FMS. A network analysis was conducted to quantify the adjusted correlations between the modeled variables and to assess the centrality indices (i.e., the degree of connection with other symptoms in the network and the importance in the system modeled as a network. This model showed several local associations between the variables. Multiple positive correlations between PPTs were observed, being the strongest weight between PPTs over the knee and tibialis anterior (ρ: 0.28). Catastrophism was associated with higher hypervigilance (ρ: 0.23) and lower health-related EuroQol-5D (ρ: −0.24). The most central variables were PPT over the tibialis anterior (the highest strength centrality), hand grip (the highest harmonic centrality) and Time Up and Go (the highest betweenness centrality). This study, applying network analysis to understand the complex mechanisms of women with FMS, supports a model where sensory-related, psychological/cognitive, health-related, and physical variables are connected. Implications of the current findings, e.g., developing treatments targeting these mechanisms, are discussed. Full article
(This article belongs to the Special Issue Chronic Pain and Fibromyalgia: Biomarkers and Pathophysiology)
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Other

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15 pages, 1252 KiB  
Systematic Review
A Systematic Review and Meta-Analysis of the Prevalence of Small Fibre Impairment in Patients with Fibromyalgia
by Eleonora Galosi, Andrea Truini and Giulia Di Stefano
Diagnostics 2022, 12(5), 1135; https://doi.org/10.3390/diagnostics12051135 - 3 May 2022
Cited by 12 | Viewed by 4869
Abstract
Converging evidence shows that patients with fibromyalgia syndrome have signs of small fibre impairment, possibly leading to pain and autonomic symptoms, with a frequency that has not yet been systematically evaluated. To fill this gap, our review aims to define the frequency of [...] Read more.
Converging evidence shows that patients with fibromyalgia syndrome have signs of small fibre impairment, possibly leading to pain and autonomic symptoms, with a frequency that has not yet been systematically evaluated. To fill this gap, our review aims to define the frequency of somatic and autonomic small fibre damage in patients with fibromyalgia syndrome, as assessed by objective small fibre-related testing. We found 360 articles on somatic and autonomic small fibre assessment in patients with fibromyalgia. Out of the 88 articles assessed for eligibility, 20 were included in the meta-analysis, involving 903 patients with fibromyalgia. The estimated prevalence of somatic small fibre impairment, as assessed with skin biopsy, corneal confocal microscopy, and microneurography, was 49% (95% confidence interval (CI): 39–60%, I2 = 89%), whereas the estimated prevalence of autonomic small fibre impairment, as assessed with heart rate variability, sympathetic skin response, skin conductance, and tilt testing, was 45% (95% CI: 25–65%, I2 = 91%). Our study shows that a considerable proportion of patients with fibromyalgia have somatic and autonomic small fibre impairment, as assessed by extensive small fibre-related testing. Nevertheless, the heterogeneity and inconsistencies across studies challenge the exact role of small fibre impairment in fibromyalgia symptoms. Full article
(This article belongs to the Special Issue Chronic Pain and Fibromyalgia: Biomarkers and Pathophysiology)
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