The role of the vagus nerve in fibromyalgia syndrome

Martins, Daniel Fernandes; Viseux, Frédéric; Salm, Daiana Cristina; Ribeiro, Anny Caroline Avelino; Silva, Helen Kassiana Lopes da; Seim, Lynsey A.; Bittencourt, Edsel B.; Bianco, Gianluca; Moré, Ari Ojeda Ocampo; Reed, William R.; Mazzardo-Martins, Leidiane

doi:10.1016/j.neubiorev.2021.10.021

Cited by 19 publications

(11 citation statements)

References 187 publications

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“…The close association between long-COVID fatigue and cognitive symptoms implies a common pathophysiology. Individuals with fibromyalgia, a syndrome that shares similarities with long-COVID, exhibit low heart rate variability (HRV) [ 17 ]. It was assumed that their symptoms are related to a low vagal tone, responsible for the low HRV and consequent affective disorders through the vagal ventral branch [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Individuals with fibromyalgia, a syndrome that shares similarities with long-COVID, exhibit low heart rate variability (HRV) [ 17 ]. It was assumed that their symptoms are related to a low vagal tone, responsible for the low HRV and consequent affective disorders through the vagal ventral branch [ 17 ]. Reduced vagal tone was also associated with cognitive impairment among individuals with ME/CFS [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

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Risk Factors and Multidimensional Assessment of Long Coronavirus Disease Fatigue: A Nested Case-Control Study

Margalit

Yelin

Sagi

et al. 2022

Clinical Infectious Diseases

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Background Fatigue is the most prevalent and debilitating long COVID symptom, however risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long COVID fatigue and explored its possible pathophysiology. Methods Nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long COVID fatigue. Results Total of 141 individuals were included. Mean age was 47 (SD 13) years; 115 (82%) were recovering from mild COVID-19. Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long COVID fatigue. They had significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness and long COVID symptoms, and of physical limitation in daily activities. Individuals with fatigue had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53), p=0.038] and oxygen consumption per Kg [27.69 (7.52) vs 30.71 (7.52), p=0.036] at peak exercise. The two independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (odds ratio [OR] 0.79 per 10 beats/minute, 95% confidence interval [CI] 0.65-0.96, p=0.019); and long COVID memory impairment (OR 3.76, 95% CI 1.57-9.01, p=0.003). Conclusions Long COVID fatigue may be related to autonomic dysfunction, impaired cognition and decreased mood. This may suggest a limbic-vagal pathophysiology. Clinical Trial registration: NCT04851561

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Risk Factors and Multidimensional Assessment of Long Coronavirus Disease Fatigue: A Nested Case-Control Study

Margalit

Yelin

Sagi

et al. 2022

Clinical Infectious Diseases

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“…Life traumas are probably related to personality tendencies, as reference is often made to a "fibromyalgic personality" (43) or a form of hyporeactivity to stress (44) that is mirrored by altered vagal activity, in line with Porges' polyvagal theory of the aetiopathogenesis of trauma (45). This has been investigated in more detail by Green et al in a study of male and female rats exposed to the early-life stress of neonatal limited bedding (NLB), who were found to have a significantly lower mechanical nociceptive threshold in skeletal muscle than adult controls previously exposed to neonatal standard bedding.…”

Section: Life Traumasmentioning

confidence: 99%

Fibromyalgia: one year in review 2022

Giorgi

Sirotti

Romano

et al. 2022

Clinical and Experimental Rheumatology

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“…The VN interlinks local and systemic immune processes between the CNS and PNS [19][20][21], and immune cells also express all of the necessary components of the cholinergic machinery [22]. Together, cholinergic mechanisms play an important role in the regulation of cytokines and antibody production [23,24], thereby modulating inflammatory processes with potential implications for FMS pathophysiology and severity [25,26].…”

Section: Introductionmentioning

confidence: 99%

Distinct CholinomiR Blood Cell Signature as a Potential Modulator of the Cholinergic System in Women with Fibromyalgia Syndrome

Erbacher

Vaknine

Moshitzky

et al. 2022

Cells

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Fibromyalgia syndrome (FMS) is a heterogeneous chronic pain syndrome characterized by musculoskeletal pain and other key co-morbidities including fatigue and a depressed mood. FMS involves altered functioning of the central and peripheral nervous system (CNS, PNS) and immune system, but the specific molecular pathophysiology remains unclear. Anti-cholinergic treatment is effective in FMS patient subgroups, and cholinergic signaling is a strong modulator of CNS and PNS immune processes. Therefore, we used whole blood small RNA-sequencing of female FMS patients and healthy controls to profile microRNA regulators of cholinergic transcripts (CholinomiRs). We compared microRNA profiles with those from Parkinson’s disease (PD) patients with pain as disease controls. We validated the sequencing results with quantitative real-time PCR (qRT-PCR) and identified cholinergic targets. Further, we measured serum cholinesterase activity in FMS patients and healthy controls. Small RNA-sequencing revealed FMS-specific changes in 19 CholinomiRs compared to healthy controls and PD patients. qRT-PCR validated miR-182-5p upregulation, distinguishing FMS patients from healthy controls. mRNA targets of CholinomiRs bone morphogenic protein receptor 2 and interleukin 6 signal transducer were downregulated. Serum acetylcholinesterase levels and cholinesterase activity in FMS patients were unchanged. Our findings identified an FMS-specific CholinomiR signature in whole blood, modulating immune-related gene expression.

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The role of the vagus nerve in fibromyalgia syndrome

Cited by 19 publications

References 187 publications

Risk Factors and Multidimensional Assessment of Long Coronavirus Disease Fatigue: A Nested Case-Control Study

Risk Factors and Multidimensional Assessment of Long Coronavirus Disease Fatigue: A Nested Case-Control Study

Fibromyalgia: one year in review 2022

Distinct CholinomiR Blood Cell Signature as a Potential Modulator of the Cholinergic System in Women with Fibromyalgia Syndrome

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