The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.

Two neuroimaging studies using functional magnetic resonance imaging (fMRI) and thermally induced pain are presented. Fifteen healthy right-handed subjects were imaged while they had to discern different levels of thermal stimuli in the first study and while they disengaged from the feeling of pain during constant stimulation in the second study. In the first experiment, during painful phasic stimuli, right-sided anterior insular activation as well as bilateral posterior insular activation could be shown regardless of stimulation side, as well as right-sided activation of sensory association areas in the superior parietal lobule. Also, activation of the ipsilateral sensorimotor cortex could be shown. In the second experiment, all subjects succeeded in suppressing the feeling of pain during previously painful levels of stimulation. During the early part of the tonic painful stimulation, bilateral activation of caudate head and dorsolateral prefrontal cortex (DLPFC) as well as insular cortex and dorsal anterior cingulated cortex (dACC) was observed. During the late part of the tonic painful stimulation, anterior insular activation as well as dACC and bilateral prefrontal cortical activation could be shown. Taken together, the activation of PFC and caudate nucleus hints at an important role in the initiation (caudate) and maintenance (PFC) of suppression of the feeling of pain. No ipsilateral sensorimotor activation could be shown in the second experiment. The possible import of unwanted sensorimotor activation due to the simultaneous rating process in the first experiment is discussed.

Pain modulation is an integral function of the nervous system. It is needed to adapt to chronic stimuli. To gain insights into pain suppression mechanisms, two studies concerning the suppression of the feeling of pain with different stimulation modalities (heat vs. electrical stimuli) but using the same stimulation paradigms were compared: 15 subjects each had been stimulated on both hands under the instruction to suppress the feeling of pain. Anterior insula and DLPFC activation was seen in both single modality studies and seems to be a common feature of pain suppression, as it is absent in the interaction analyses presented here. During the task to suppress the feeling of pain, there were no consistent activations stronger under thermostimulation. But during electrostimulation, there was significantly stronger activation than during thermal stimulation in the caudate nucleus bilaterally and in the contralateral posterior insula. This may be attributed to the higher sensory-discriminative content and more demand on subjective rating and suppression of the painful electrical stimulus, compared to thermostimulation. The caudate nucleus seems to play an important role not only in the motor system but also in the modulation of the pain experience.

Abstract. Defect localisation is essential in software engineering and is an important task in domain-specific data mining. Existing techniques building on call-graph mining can localise different kinds of defects. However, these techniques focus on defects that affect the controlflow and are agnostic regarding the dataflow. In this paper, we introduce dataflowenabled call graphs that incorporate abstractions of the dataflow. Building on these graphs, we present an approach for defect localisation. The creation of the graphs and the defect localisation are essentially data mining problems, making use of discretisation, frequent subgraph mining and feature selection. We demonstrate the defect-localisation qualities of our approach with a study on defects introduced into Weka. As a result, defect localisation now works much better, and a developer has to investigate on average only 1.5 out of 30 methods to fix a defect.

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