MicroRNA-Related Polymorphism and Their Association with Fibromyalgia.

MicroRNAs are tissue-specific expressed short RNAs that serve post-transcriptional gene regulation. A specific microRNA can bind to mRNAs of different genes and thereby suppress their protein production. In the context of the complex phenotype of fibromyalgia, we used the Axiom miRNA Target Site Genotyping Array to search genome-wide for DNA variations in microRNA genes, their regulatory regions, and in the 3'UTR of protein-coding genes. To identify disease-relevant DNA polymorphisms, a cohort of 176 female fibromyalgia patients was studied in comparison to a cohort of 162 healthy women. The association between 48,329 markers and fibromyalgia was investigated using logistic regression adjusted for population stratification. Results show that 29 markers had p-values < 1 × 10-3, and the strongest association was observed for rs758459 (p-value of 0.0001), located in the Neurogenin 1 gene which is targeted by hsa-miR-130a-3p. Furthermore, variant rs2295963 is predicted to affect binding of hsa-miR-1-3p. Both microRNAs were previously reported to be differentially expressed in fibromyalgia patients. Despite its limited statistical power, this study reports two microRNA-related polymorphisms which may play a functional role in the pathogenesis of fibromyalgia. For a better understanding of the disease pattern, further functional analyses on the biological significance of microRNAs and microRNA-related polymorphisms are required.

Adverse effects of the COVID-19 pandemic on fibromyalgia patients in Germany: a longitudinal investigation including pre-pandemic data of pain and health-related outcomes.

OBJECTIVES: The COVID-19 pandemic, along with the associated restrictions and changes, has had a far-reaching impact on the mental health and well-being of people around the world. The most serious impact can arguably be observed in vulnerable populations, such as chronic pain patients. Using a pre-test/post-test design with pre-pandemic comparative data, the present study sought to investigate how the pandemic impacted chronic pain and well-being in individuals with fibromyalgia (FM) (N = 109). METHODS: We assessed longitudinal changes of various clinical parameters, such as pain severity, disability, FM impact, depressive mood and several items assessing the individual experience of the pandemic as well as self-perceived changes of pain, anxiety, depression and physical activity levels. RESULTS: Results suggested a significant self-perceived worsening of pain, depressive mood, anxiety as well as reduced physical activity due to the pandemic. Interestingly, these self-perceived changes were not reflected in longitudinal increases of test values (T1-T2). Pain severity at T1 was the strongest predictor of pain severity at T2, while COVID-related outcomes showed no critical importance, with COVID-related fear being the only significant predictor of T2 pain. The general perceived negative impact of the pandemic was the only predictor of self-perceived worsening of pain. Finally, patients with less severe pre-pandemic pain symptoms displayed greater longitudinal worsening of pain. CONCLUSIONS: These findings emphasise the importance of addressing the specific needs of chronic pain suffers during a pandemic.

Brain morphometric changes in fibromyalgia and the impact of psychometric and clinical factors: a volumetric and diffusion-tensor imaging study.

BACKGROUND: Previous studies have repeatedly found distinct brain morphometric changes in patients with fibromyalgia (FM), mainly affecting gray and white matter abnormalities in areas related to sensory and affective pain processing. However, few studies have thus far linked different types of structural changes and not much is known about behavioral and clinical determinants that might influence the emergence and progression of such changes. METHODS: We used voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) to detect regional patterns of (micro)structural gray (GM) and white matter (WM) alterations in 23 patients with FM compared to 21 healthy controls (HC), while considering the influence of demographic, psychometric, and clinical variables (age, symptom severity, pain duration, heat pain threshold, depression scores). RESULTS: VBM and DTI revealed striking patterns of brain morphometric changes in FM patients. Bilateral middle temporal gyrus (MTG), parahippocampal gyrus, left dorsal anterior cingulate cortex (dACC), right putamen, right caudate nucleus, and left dorsolateral prefrontal cortex (DLPFC) showed significantly decreased GM volumes. In contrast, increased GM volume was observed in bilateral cerebellum and left thalamus. Beyond that, patients displayed microstructural changes of WM connectivity within the medial lemniscus, corpus callosum, and tracts surrounding and connecting the thalamus. Sensory-discriminative aspects of pain (pain severity, pain thresholds) primarily showed negative correlations with GM within bilateral putamen, pallidum, right midcingulate cortex (MCC), and multiple thalamic substructures, whereas the chronicity of pain was negatively correlated with GM volumes within right insular cortex and left rolandic operculum. Affective-motivational aspects of pain (depressive mood, general activity) were related to GM and FA values within bilateral putamen and thalamus. CONCLUSIONS: Our results suggest a variety of distinct structural brain changes in FM, particularly affecting areas involved in pain and emotion processing such as the thalamus, putamen, and insula.

Neural correlates of control over pain in fibromyalgia patients.

The perceived lack of control over the experience of pain is arguably-one major cause of agony and impaired life quality in patients with chronic pain disorders as fibromyalgia (FM). The way perceived control affects subjective pain as well as the underlying neural mechanisms have so far not been investigated in chronic pain. We used functional magnetic resonance imaging (fMRI) to examine the neural correlates of self-controlled compared to computer-controlled heat pain in healthy controls (HC, n = 21) and FM patients (n = 23). Contrary to HC, FM failed to activate brain areas usually involved in pain modulation as well as reappraisal processes (right ventrolateral (VLPFC), dorsolateral prefrontal cortex (DLPFC) and dorsal anterior cingulate cortex (dACC)). Computer-controlled (compared to self-controlled) heat revealed significant activations of the orbitofrontal cortex (OFC) in HC, whereas FM activated structures that are typically involved in neural emotion processing (amygdala, parahippocampal gyrus). Additionally, FM displayed disrupted functional connectivity (FC) of the VLPFC, DLPFC and dACC with somatosensory and pain (inhibition)-related areas during self-controlled heat stimulation as well as significantly decreased gray matter (GM) volumes compared to HC in DLPFC and dACC. The described functional and structural changes provide evidence for far-reaching impairments concerning pain-modulatory processes in FM. Our investigation represents a first demonstration of dysfunctional neural pain modulation through experienced control in FM according to the extensive functional and structural changes in relevant sensory, limbic and associative brain areas. These areas may be targeted in clinical pain therapeutic methods involving TMS, neurofeedback or cognitive behavioral trainings.