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Background Fibromyalgia syndrome (FMS) is frequently associated with psychiatric conditions, particularly anxiety. Deficits in contingency learning during fear conditioning have been hypothesized to increase anxiety and, consequently, pain sensation in susceptible individuals. The goal of this study was to examine the relationship between contingency learning and pain experience in subjects with FMS and rheumatoid arthritis (RA). Methods Fourteen female FMS subjects, 14 age-matched female RA subjects and 14 age-matched female healthy controls (HCs) were included in a fear-conditioning experiment. The conditioned stimulus (CS) consisted of visual signs, the unconditioned stimulus (US) of thermal stimuli. CS− predicted low-temperature exposure (US), while CS+ was followed by low or high temperature. Results In the FMS group, only 50% of the subjects were aware of the US–CS contingency, whereas 86% of the RA subjects and all of the HCs were aware of the contingency. CS+ induced more anxiety than CS− in RA subjects and HCs. As expected, low-temperature exposure was experienced as less painful after CS− than after CS+ in these subjects. FMS subjects did not show such adaptive conditioning. The effects of the type of CS on heart rate changes were significant in the HCs and the aware FMS subjects, but not in the unaware FMS subjects. Conclusions Contingency learning deficits represent a potentially promising and specific, but largely unstudied, psychopathological factor in FMS. Deficits in contingency learning may increase anxiety and, consequently, pain sensation. These findings have the potential to contribute to the development of novel therapeutic approaches for FMS.

The current fMRI study investigated cortical processing of electrically induced painful tooth stimulation of both maxillary canines and central incisors in 21 healthy, right-handed volunteers. A constant current, 150% above tooth specific pain perception thresholds was applied and corresponding online ratings of perceived pain intensity were recorded with a computerized visual analog scale during fMRI measurements. Lateralization of cortical activations was investigated by a region of interest analysis. A wide cortical network distributed over several areas, typically described as the pain or nociceptive matrix, was activated on a conservative significance level. Distinct lateralization patterns of analyzed structures allow functional classification of the dental pain processing system. Namely, certain parts are activated independent of the stimulation site, and hence are interpreted to reflect cognitive emotional aspects. Other parts represent somatotopic processing and therefore reflect discriminative perceptive analysis. Of particular interest is the observed amygdala activity depending on the stimulated tooth that might indicate a role in somatotopic encoding. Based on the model of a lateral and medial pain system, we hypothesized that within the cortical pain circuitry, certain brain areas be activated dependent on the stimulation side and others showing lateralized or bilateral hemispheric activity independent of the side of stimulus application. MaterIals and Methods PartIcIPantsTwenty-one neurologically healthy subjects (8 female/13 male, age 20-44, all right-handed (Annett, 1970) with no dental pain experience during the preceding year participated in the experiment. Inclusion criteria required test teeth to be caries free, vital, and without attachment loss. Dental and periodontal pathologies were excluded by professional dental and radiographic examinations of maxillary teeth. Subjects received detailed information about the experimental procedure and provided written informed consent. The study was approved by the local ethics committee and was conducted according to the guidelines of the Declaration of Helsinki for treatment of experimental human subjects. exPerIMental MaterIalMaxillary alginate impressions were taken from the subjects' dentitions for fabrication of soft dental acrylic splints. Four pairs of stainless steel electrodes were embedded in each individual dental splint opposite the labial and palatal surface center of the target teeth, namely maxillary canines and central incisors (Figure 1). They served as anode and cathode during electric stimulation. In order to minimize electric resistance during stimulation, a round piece of hydrogel (AG602-6, AMGEL Technologies, Lystrup, Denmark) with 3 mm diameter was placed between the tooth and anode and cathode, respectively, and was covered with a thin layer of toothpaste (Signal Microgranuli, Unilever, Zug, Switzerland).Electric stimulation was performed by means of the portable system Compex Motion System (Keller et al., 2002) and the exper...

Identification of brain regions that differentially respond to pain intensity may improve our understanding of trigeminally mediated nociception. This report analyzed cortical responses to painless and painful electrical stimulation of a right human maxillary canine tooth. Functional magnetic resonance images were obtained during the application of five graded stimulus strengths, from below, at, and above the individually determined pain thresholds. Study participants reported each stimulus on a visual rating scale with respect to evoked sensation. Based on hemodynamic responses of all pooled stimuli, a cerebral network was identified that largely corresponds to the known lateral and medial nociceptive system. Further analysis of the five graded stimulus strengths revealed positive linear correlations for the anterior insula bilaterally, the contralateral (left) anterior mid-cingulate, as well as contralateral (left) pregenual cingulate cortices. Cerebral toothache intensity coding on a group level can thus be attributed to specific subregions within the cortical pain network.