Dataset Information

Altered central pain processing in fibromyalgia-A multimodal neuroimaging case-control study using arterial spin labelling.

ABSTRACT: Fibromyalgia is characterized by chronic pain and a striking discrepancy between objective signs of tissue damage and severity of pain. Function and structural alterations in brain areas involved in pain processing may explain this feature. Previous case-control studies in fibromyalgia focused on acute pain processing using experimentally-evoked pain paradigms. Yet, these studies do not allow conclusions about chronic, stimulus-independent pain. Resting-state cerebral blood flow (rsCBF) acquired by arterial spin labelling (ASL) may be a more accurate marker for chronic pain. The objective was to integrate four different functional and structural neuroimaging markers to evaluate the neural correlate of chronic, stimulus-independent pain using a resting-state paradigm. In line with the pathophysiological concept of enhanced central pain processing we hypothesized that rsCBF is increased in fibromyalgia in areas involved in processing of acute pain. We performed an age matched case-control study of 32 female fibromyalgia patients and 32 pain-free controls and calculated group differences in rsCBF, resting state functional connectivity, grey matter volume and cortical thickness using whole-brain and region of interest analyses. We adjusted all analyses for depression and anxiety. As centrally acting drugs are likely to interfere with neuroimaging markers, we performed a subgroup analysis limited to patients not taking such drugs. We found no differences between cases and controls in rsCBF of the thalamus, the basal ganglia, the insula, the somatosensory cortex, the prefrontal cortex, the anterior cingulum and supplementary motor area as brain areas previously identified to be involved in acute processing in fibromyalgia. The results remained robust across all neuroimaging markers and when limiting the study population to patients not taking centrally acting drugs and matched controls. In conclusion, we found no evidence for functional or structural alterations in brain areas involved in acute pain processing in fibromyalgia that could reflect neural correlates of chronic stimulus-independent pain.

SUBMITTER: Muller M

PROVIDER: S-EPMC7853499 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Altered central pain processing in fibromyalgia-A multimodal neuroimaging case-control study using arterial spin labelling.

Müller Monika M Wüthrich Florian F Federspiel Andrea A Wiest Roland R Egloff Niklaus N Reichenbach Stephan S Exadaktylos Aristomenis A Jüni Peter P Curatolo Michele M Walther Sebastian S

PloS one 20210202 2

Fibromyalgia is characterized by chronic pain and a striking discrepancy between objective signs of tissue damage and severity of pain. Function and structural alterations in brain areas involved in pain processing may explain this feature. Previous case-control studies in fibromyalgia focused on acute pain processing using experimentally-evoked pain paradigms. Yet, these studies do not allow conclusions about chronic, stimulus-independent pain. Resting-state cerebral blood flow (rsCBF) acquired ...[more]

PMID: 33529254

Similar Datasets

Project description:BACKGROUND:Diffusion- and perfusion-weighted MRI are valuable tools for measuring the cellular and vascular properties of brain tumours. This has been well studied in adult patients, however, the biological features of childhood brain tumours are unique, and paediatric-focused studies are less common. We aimed to assess the diagnostic utility of apparent diffusion coefficient (ADC) values derived from diffusion-weighted imaging (DWI) and cerebral blood flow (CBF) values derived from arterial spin labelling (ASL) in paediatric brain tumours. METHODS:We performed a meta-analysis of published studies reporting ADC and ASL-derived CBF values in paediatric brain tumours. Data were combined using a random effects model in order to define typical parameter ranges for different histological tumour subtypes and WHO grades. New data were also acquired in a 'validation cohort' at our institution, in which ADC and CBF values in treatment naïve paediatric brain tumour patients were measured, in order to test the validity of the findings from the literature in an un-seen cohort. ADC and CBF quantification was performed by two radiologists via manual placement of tumour regions of interest (ROIs), in addition to an automated approach to tumour ROI placement. RESULTS:A total of 14 studies met the inclusion criteria for the meta-analysis, constituting data acquired in 542 paediatric patients. Parameters of interest were based on measurements from ROIs placed within the tumour, including mean and minimum ADC values (ADCROI-mean, ADCROI-min) and the maximum CBF value normalised to grey matter (nCBFROI-max). After combination of the literature data, a number of histological tumour subtype groups showed significant differences in ADC values, which were confirmed, where possible, in our validation cohort of 32 patients. In both the meta-analysis and our cohort, diffuse midline glioma was found to be an outlier among high-grade tumour subtypes, with ADC and CBF values more similar to the low-grade tumours. After grouping patients by WHO grade, significant differences in grade groups were found in ADCROI-mean, ADCROI-min, and nCBFROI-max, in both the meta-analysis and our validation cohort. After excluding diffuse midline glioma, optimum thresholds (derived from ROC analysis) for separating low/high-grade tumours were 0.95 × 10-3 mm2/s (ADCROI-mean), 0.82 × 10-3 mm2/s (ADCROI-min) and 1.45 (nCBFROI-max). These thresholds were able to identify low/high-grade tumours with 96%, 83%, and 83% accuracy respectively in our validation cohort, and agreed well with the results from the meta-analysis. Diagnostic power was improved by combining ADC and CBF measurements from the same tumour, after which 100% of tumours in our cohort were correctly classified as either low- or high-grade (excluding diffuse midline glioma). CONCLUSION:ADC and CBF values are useful for differentiating certain histological subtypes, and separating low- and high-grade paediatric brain tumours. The threshold values presented here are in agreement with previously published studies, as well as a new patient cohort. If ADC and CBF values acquired in the same tumour are combined, the diagnostic accuracy is optimised.

Project description:Inability to predict the therapeutic effect of a drug in individual pain patients prolongs the process of drug and dose finding until satisfactory pharmacotherapy can be achieved. Many chronic pain conditions are associated with hypersensitivity of the nervous system or impaired endogenous pain modulation. Pharmacotherapy often aims at influencing these disturbed nociceptive processes. Its effect might therefore depend on the extent to which they are altered. Quantitative sensory testing (QST) can evaluate various aspects of pain processing and might therefore be able to predict the analgesic efficacy of a given drug. In the present study three drugs commonly used in the pharmacological management of chronic low back pain are investigated. The primary objective is to examine the ability of QST to predict pain reduction. As a secondary objective, the analgesic effects of these drugs and their effect on QST are evaluated.In this randomized, double blinded, placebo controlled cross-over study, patients with chronic low back pain are randomly assigned to imipramine, oxycodone or clobazam versus active placebo. QST is assessed at baseline, 1 and 2 h after drug administration. Pain intensity, side effects and patients' global impression of change are assessed in intervals of 30 min up to two hours after drug intake. Baseline QST is used as explanatory variable to predict drug effect. The change in QST over time is analyzed to describe the pharmacodynamic effects of each drug on experimental pain modalities. Genetic polymorphisms are analyzed as co-variables.Pharmacotherapy is a mainstay in chronic pain treatment. Antidepressants, anticonvulsants and opioids are frequently prescribed in a "trial and error" fashion, without knowledge however, which drug suits best which patient. The present study addresses the important need to translate recent advances in pain research to clinical practice. Assessing the predictive value of central hypersensitivity and endogenous pain modulation could allow for the implementation of a mechanism-based treatment strategy in individual patients.Clinicaltrials.gov, NCT01179828.

Project description:BackgroundNeuroimaging studies reliably identify two markers of error commission: the error-related negativity (ERN), an event-related potential, and functional MRI activation of the dorsal anterior cingulate cortex (dACC). While theorized to reflect the same neural process, recent evidence suggests that the ERN arises from the posterior cingulate cortex not the dACC. Here, we tested the hypothesis that these two error markers also have different genetic mediation.MethodsWe measured both error markers in a sample of 92 comprised of healthy individuals and those with diagnoses of schizophrenia, obsessive-compulsive disorder or autism spectrum disorder. Participants performed the same task during functional MRI and simultaneously acquired magnetoencephalography and electroencephalography. We examined the mediation of the error markers by two single nucleotide polymorphisms: dopamine D4 receptor (DRD4) C-521T (rs1800955), which has been associated with the ERN and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133), which has been associated with error-related dACC activation. We then compared the effects of each polymorphism on the two error markers modeled as a bivariate response.ResultsWe replicated our previous report of a posterior cingulate source of the ERN in healthy participants in the schizophrenia and obsessive-compulsive disorder groups. The effect of genotype on error markers did not differ significantly by diagnostic group. DRD4 C-521T allele load had a significant linear effect on ERN amplitude, but not on dACC activation, and this difference was significant. MTHFR C677T allele load had a significant linear effect on dACC activation but not ERN amplitude, but the difference in effects on the two error markers was not significant.ConclusionsDRD4 C-521T, but not MTHFR C677T, had a significant differential effect on two canonical error markers. Together with the anatomical dissociation between the ERN and error-related dACC activation, these findings suggest that these error markers have different neural and genetic mediation.

Project description:Non-convulsive status epilepticus describes the syndrome of unexplained impaired consciousness in critically ill patients. Non-convulsive status epilepticus is very likely to lead to delayed diagnosis and poor outcomes because of the absence of convulsive symptoms. EEG is essential for the diagnosis of non-convulsive status epilepticus to establish the association between periodic discharges and rhythmic delta activity in addition to ictal epileptiform discharges according to the Salzburg criteria. Arterial spin labelling, a type of perfusion MRI, has been applied for rapid and non-invasive evaluation of the ictal state. Ictal cerebral cortical hyperperfusion is the most common finding to demonstrate focal onset seizures. Hyperperfusion of the thalamus on single photon emission computed tomography was found in patients with impaired awareness seizures. We hypothesized that thalamocortical hyperperfusion on arterial spin labelling identifies non-convulsive status epilepticus and such thalamic hyperperfusion specifically associates with periodic/rhythmic discharges producing impaired consciousness without convulsion. We identified 27 patients (17 females; age, 39-91 years) who underwent both arterial spin labelling and EEG within 24 h of suspected non-convulsive status epilepticus. We analysed 28 episodes of suspected non-convulsive status epilepticus and compared hyperperfusion on arterial spin labelling with periodic/rhythmic discharges. We evaluated 21 episodes as a positive diagnosis of non-convulsive status epilepticus according to the Salzburg criteria. We identified periodic discharges in 15 (12 lateralized and 3 bilateral independent) episodes and rhythmic delta activity in 13 (10 lateralized, 1 bilateral independent and 2 generalized) episodes. Arterial spin labelling showed thalamic hyperperfusion in 16 (11 unilateral and 5 bilateral) episodes and cerebral cortical hyperperfusion in 24 (20 unilateral and 4 bilateral) episodes. Thalamic hyperperfusion was significantly associated with non-convulsive status epilepticus (P = 0.0007; sensitivity, 76.2%; specificity, 100%), periodic discharges (P < 0.0001; 93.3%; 84.6%), and rhythmic delta activity (P = 0.0006; 92.3%; 73.3%). Cerebral cortical hyperperfusion was significantly associated with non-convulsive status epilepticus (P = 0.0017; 100%; 57.1%) and periodic discharges (P = 0.0349; 100%; 30.8%), but not with rhythmic delta activity. Thalamocortical hyperperfusion could be a new biomarker of non-convulsive status epilepticus according to the Salzburg criteria in critically ill patients. Specific thalamic hyperexcitability might modulate the periodic discharges and rhythmic delta activity associated with non-convulsive status epilepticus. Impaired consciousness without convulsions could be caused by predominant thalamic hyperperfusion together with cortical hyperperfusion but without ictal epileptiform discharges.

Dataset Information

Altered central pain processing in fibromyalgia-A multimodal neuroimaging case-control study using arterial spin labelling.

Publications

Altered central pain processing in fibromyalgia-A multimodal neuroimaging case-control study using arterial spin labelling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets