RESUMEN
OBJECTIVE: Muscle pain differs from skin pain with respect to quality, accuracy of localization, and unpleasantness. This study was conducted to identify the brain regions associated with the affective-motivational component of tonic skin and muscle pain. METHODS: Forty healthy volunteers were investigated in three groups with different F-18 fluorodeoxyglucose PET activation scans. A verbal rating scale (VRS) was used to quantify pain intensity and unpleasantness. One group was investigated during painful infusion of an acidified phosphate buffer (pH 5.2) into either muscle or skin for 30 minutes. Muscle and skin infusions were adjusted to achieve pain intensity rating of VRS = 40. The second group received sham stimulation of muscle and skin by infusion of non-acidified phosphate buffer (pH 7.3 to 7.4, pain intensity = 0). The third group underwent only one PET scan without sensory stimulation. RESULTS: Unpleasantness ratings were higher (VRS 38.3 vs 25.5) during IM compared to intracutaneous stimulation, despite the same pain intensity (VRS = 40). Sham stimulation revealed no pain or unpleasantness. Regional cerebral glucose metabolism during sham stimulation showed similar findings for intracutaneous and IM infusions with significant activations of the bilateral anterior cingulate, bilateral frontal (premotor) cortex, and the ipsilateral parietal operculum. The comparison of pain vs sham stimulation revealed activations of the bilateral insula for IM but not intracutaneous stimulation. The unpleasantness perception in skin and muscle stimulation was positively correlated to the bilateral insular metabolism. CONCLUSION: The data suggest that the insula represents one main structure where the unpleasantness of tonic pain perception is encoded.
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Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Emociones/fisiología , Dolor/diagnóstico por imagen , Dolor/fisiopatología , Ácidos/efectos adversos , Enfermedad Aguda , Adulto , Mapeo Encefálico , Tampones (Química) , Enfermedad Crónica , Femenino , Fluorodesoxiglucosa F18 , Lateralidad Funcional/fisiología , Glucosa/metabolismo , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético/inervación , Músculo Esquelético/fisiopatología , Nociceptores/efectos de los fármacos , Nociceptores/fisiología , Dolor/metabolismo , Dimensión del Dolor/métodos , Tomografía de Emisión de Positrones , Valores de Referencia , Piel/inervación , Piel/fisiopatología , Factores de TiempoRESUMEN
OBJECTIVES: To evaluate cerebral glucose metabolism, assessed by 18-fluorodeoxyglucose positron emission tomography (FDG-PET), in patients with chronic fatigue syndrome (CFS), using an observer independent analytical approach; and to characterise any observed alterations by correlating them with neuropsychological deficits. METHODS: 26 patients (13 female, 13 male) were examined. They all fulfilled the CDC diagnostic criteria for CFS. Their ages ranged from 26 to 61 years (mean (SD) age, 43 (9.3) years). They underwent extensive psychometric testing including the hospital anxiety and depression scale (HADS) and the short form 36 item health questionnaire (SF-36). Brain FDG-PET was done in all the subjects. After stereotactic normalisation, single subject comparisons with an age and sex matched normal database (n = 18) and a group comparison between the patients and normal controls were undertaken, along with additional correlation analyses between brain metabolism and psychometric test scores. RESULTS: 12 of the 26 patients showed no significant decrease in FDG uptake compared with the controls. Of the remaining 14, 12 showed hypometabolism bilaterally in the cingulate gyrus and the adjacent mesial cortical areas. Five of these 12 patients also had decreased metabolism in the orbitofrontal cortex. The two remaining patients had hypometabolism in the cuneus/praecuneus. Correlation analyses showed significant correlations between some test scores (anxiety, depression, health related quality of life) but not fatigue and regional reductions in glucose metabolism. CONCLUSIONS: Although abnormalities in FDG-PET were only detectable in approximately half the CFS patients examined, and no specific pattern for CFS could be identified, PET may provide valuable information in helping to separate CFS patients into subpopulations with and without apparent alterations in the central nervous system.
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Encéfalo/metabolismo , Síndrome de Fatiga Crónica/fisiopatología , Glucosa/metabolismo , Adulto , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos , Tomografía Computarizada de EmisiónRESUMEN
5-(2'-[18F]Fluoroethyl)flumazenil ([18F]FEF) is a fluorine-18 labelled positron emission tomography (PET) tracer for central benzodiazepine receptors. Compared with the established [11C]flumazenil, it has the advantage of the longer half-life of the fluorine-18 label. After optimisation of its synthesis and determination of its in vitro receptor affinities, we performed first PET studies in humans. PET studies in seven healthy human volunteers were performed on a Siemens ECAT EXACT whole-body scanner after injection of 100-280 MBq [L8F]FEF. In two subjects, a second PET scan was conducted after pretreatment with unlabelled flumazenil (1 mg or 2.5 mg i.v., 3 min before tracer injection). A third subject was studied both with [18F]FEF and with [11C]flumazenil. Brain radioactivity was measured for 60-90 min p.i. and analysed with a region of interest-oriented approach and on a voxelwise basis with spectral analysis. Plasma radioactivity was determined from arterial blood samples and metabolites were determined by high-performance liquid chromatography. In human brain, maximum radioactivity accumulation was observed 4 +/- 2 min p.i., with a fast clearance kinetics resulting in 50% and 20% of maximal activities at about 10 and 30 min, respectively. [18F]FEF uptake followed the known central benzodiazepine receptor distribution in the human brain (occipital cortex >temporal cortex >cerebellum >thalamus >pons). Pretreatment with unlabelled flumazenil resulted in reduced tracer uptake in all brain areas except for receptor-free reference regions like the pons. Parametric images of distribution volume and binding potential generated on a voxelwise basis revealed two- to three-fold lower in vivo receptor binding of [18F]FEF compared with [11C]flumazenil, while relative uptake of [18F]FEF was higher in the cerebellum, most likely owing to its relatively higher affinity for benzodiazepine receptors containing the alpha6 subunit. Metabolism of [18F]FEF was very rapid. Polar metabolites represented about 50%-60% of total plasma radioactivity at 5 min and 80%-90% at 20 min p.i. Although [11C]flumazenil has some advantages over [18F]FEF (higher affinity, slower metabolism, slower kinetics), our results indicate that [18F]FEF is a suitable PET ligand for quantitative assessment of central benzodiazepine receptors, which can be used independently of an on-site cyclotron.
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Encéfalo/diagnóstico por imagen , Flumazenil , Radiofármacos , Receptores de GABA-A/análisis , Tomografía Computarizada de Emisión/métodos , Flumazenil/análogos & derivados , Humanos , MasculinoRESUMEN
BACKGROUND: The current study investigated dose-dependent effects of the mu-selective agonist remifentanil on regional cerebral blood flow (rCBF) in volunteers using positron emission tomography (PET). METHODS: Ten right-handed male volunteers were included in a 15O-water PET study. Seven underwent three conditions: control (saline), low remifentanil (0.05 microg x kg(-1) x min(-1)), and moderate remifentanil (0.15 microg x kg(-1) x min(-1)). The remaining three participated in the low and moderate conditions. A semirandomized study protocol was used with control and remifentanil conditions 3 or more months apart. The order of low and moderate conditions was randomized. Cardiovascular and respiratory parameters were monitored. Categoric comparisons between the control, low, and moderate conditions and a pixelwise correlation analysis across the three conditions were performed (P < 0.05, corrected for multiple comparisons) using statistical parametric mapping. RESULTS: Cardiorespiratory parameters were maintained constant over time. At the low remifentanil dose, significant increases in relative rCBF were noted in the lateral prefrontal cortices, inferior parietal cortices, and supplementary motor area. Relative rCBF decreases were observed in the basal mediofrontal cortex, cerebellum, superior temporal lobe, and midbrain gray matter. Moderate doses further increased rCBF in mediofrontal and anterior cingulate cortices, occipital lobe transition, and caudal periventricular grey. Significant decreases were detected in the inferior parietal lobes. These dose-dependent effects of remifentanil on rCBF were confirmed by a correlation analysis. CONCLUSION: Remifentanil induced dose-dependent changes in relative rCBF in areas involved in pain processing. At moderate doses, rCBF responses were additionally detected in structures known to participate in modulation of vigilance and alertness. Insight into the mechanisms of opioid analgesia within the pain-processing neural network may lead to a better understanding of antinociception and opioid treatment.
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Analgésicos Opioides/farmacología , Circulación Cerebrovascular/efectos de los fármacos , Piperidinas/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Masculino , RemifentaniloRESUMEN
Brain imaging with positron emission tomography has identified some of the principal cerebral structures of a central network activated by pain. To discover whether the different cortical and subcortical areas process different components of the multidimensional nature of pain, we performed a regression analysis between noxious heat-related regional blood flow increases and experimental pain parameters reflecting detection of pain, encoding of pain intensity, as well as pain unpleasantness. The results of our activation study indicate that different functions in pain processing can be attributed to different brain regions; ie, the gating function reflected by the pain threshold appeared to be related to anterior cingulate cortex, the frontal inferior cortex, and the thalamus, the coding of pain intensity to the periventricular gray as well as to the posterior cingulate cortex, and the encoding of pain unpleasantness to the posterior sector of the anterior cingulate cortex.