Phasic and Tonic Pain Differentially Impact the Interruptive Function of Pain

<div><p>The interruptive effect of painful experimental stimulation on cognitive processes is a well-known phenomenon. This study investigated the influence of pain duration on the negative effects of pain on cognition. Thirty-four healthy volunteers performed a rapid serial visual presentation task (RSVP) in which subjects had to detect (visual detection task) and count the occurrence of a target letter (working memory task) in two separate sessions while being stimulated on the left volar forearm with either short (2 sec) or long (18 sec) painful heat stimuli of equal subjective intensity. The results show that subjects performed significantly worse in the long pain session as indexed by decreased detection and counting performance. Interestingly, this effect on performance was also observed during control trials of the long pain session in which participants did not receive any painful stimulation. Moreover, subjects expected long painful stimulation to have a greater impact on their performance and individual expectation correlated with working memory performance. These findings suggest that not only the length of painful stimulation but also its expected ability to impair cognitive functioning might influence the interruptive function of pain. The exact relevance of expectation for the detrimental effects of pain on cognitive processes needs to be explored in more detail in future studies.</p></div

Data from pain-related and anxiety-related questionnaires.

<p>STAI A: State anxiety; STAI B: Trait anxiety; PCS: Pain catastrophizing scale; PASS: Pain anxiety symptoms scale, D1: Fearful appraisal of pain, D2: Cognitive anxiety, D3: Physiological anxiety, D4: Escape and avoidance behavior.</p><p>Data from pain-related and anxiety-related questionnaires.</p

Experimental procedure.

<p>The experiment was divided into two sessions. In one session short painful stimulation was applied over 2 sec while in the other session long painful stimulation was applied over 18sec while subjects had to perform a rapid serial visual presentation task (RSVP). In this task, subjects detected the target letter ‘A’ within a stream of letters presented in an individually calibrated presentation speed. Detection was indicated by pressing the left mouse button as fast as possible (detection task). In addition subjects were asked to memorize and indicate the appearance of the target letter ‘A’ (1, 2 or 3) presented within one trial using the numbers on the keyboard (counting task). Within the long pain session painful stimulation comprised five consecutive trials, while short painful stimulation comprised only one trial. Pain intensity ratings were obtained following every painful and non-painful control trial.</p

Task performance correlates with individual expectation.

<p>Correlation between the subjects’ expectation about the influence of pain on task performance and the actual performance difference in the counting task between painful and non-painful trials showing that the more subjects expect pain to disturb their performance the worse their short-term memory performance is under pain.</p

Task performance.

<p>A: Counting accuracy (M ± SEM in % correct answers) in long and short pain session. Subjects perform significantly worse under pain and significantly worse in the long pain session (main effect of PAIN and STIMULATION). B: Detection accuracy (M ± SEM in % correct detections). Performance significantly decreased with painful stimulation and in the long pain session (main effect of DURATION and STIMULATION).</p

Additional file 1: of Measuring patients’ priorities using the Analytic Hierarchy Process in comparison with Best-Worst-Scaling and rating cards: methodological aspects and ranking tasks

Description of the AHP criteria. (DOCX 15 kb

Additional file 2: of Measuring patients’ priorities using the Analytic Hierarchy Process in comparison with Best-Worst-Scaling and rating cards: methodological aspects and ranking tasks

Aggregation level and different means. (DOCX 13 kb

Additional file 1: of Comparison of different approaches applied in Analytic Hierarchy Process – an example of information needs of patients with rare diseases

Questionnaire. (PDF 556 kb

Rolling Circle Amplification Tailored for Plasmonic Biosensors: From Ensemble to Single-Molecule Detection

We report on the tailoring of rolling circle amplification (RCA) for affinity biosensors relying on the optical probing of their surface with confined surface plasmon field. Affinity capture of the target analyte at the metallic sensor surface (e.g., by using immunoassays) is followed by the RCA step for subsequent readout based on increased refractive index (surface plasmon resonance, SPR) or RCA-incorporated high number of fluorophores (in surface plasmon-enhanced fluorescence, PEF). By combining SPR and PEF methods, this work investigates the impact of the conformation of long RCA-generated single-stranded DNA (ssDNA) chains to the plasmonic sensor response enhancement. In order to confine the RCA reaction within the evanescent surface plasmon field and hence maximize the sensor response, an interface carrying analyte-capturing molecules and additional guiding ssDNA strands (complementary to the repeating segments of RCA-generated chains) is developed. When using the circular padlock probe as a model target analyte, the PEF readout shows that the reported RCA implementation improves the limit of detection (LOD) from 13 pM to high femtomolar concentration when compared to direct labeling. The respective enhancement factor is of about 2 orders of magnitude, which agrees with the maximum number of fluorophore emitters attached to the RCA chain that is folded in the evanescent surface plasmon field by the developed biointerface. Moreover, the RCA allows facile visualizing of individual binding events by fluorescence microscopy, which enables direct counting of captured molecules. This approach offers a versatile route toward a fast digital readout format of single-molecule detection with further reduced LOD