Descriptive statistics of the behavioural data (Proportion of all trials, standard deviation in parentheses, confidence ratings: 1: high confidence old, 6: high confidence new).

*<p>the proportions for both old and new items do not sum up to 100 due to missing responses in the time window of 6 s.</p

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

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

Experimental design.

<p>The experiment consisted of three blocks á six painful heat stimuli ( = test stimuli) applied to the right forearm. During block one and three only the test stimuli were applied, whereas in block two a concomitant cold pressor task to the contralateral foot was applied as conditioning stimulus. Pain ratings were obtained of each test stimulus and once of the conditioning stimulus in the middle of block two. Before the actual experiment started, the a priori expectation of each participant regarding pain intensities of test stimuli during the cold pressor task was assessed.</p

The effect of treatment history on analgesic outcome is reflected in pain-related responses in the posterior insula.

<p>FMRI revealed less reduction of pain-related BOLD activity (t-scores) on the treated compared to the untreated site following a negative treatment history compared to a positive treatment history. Activation related to the ‘group-by-condition-interaction’ contrast <i>[Positive group [untreated>treated site]>Negative group [untreated>treated site]],</i> for details see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109014#pone-0109014-t001" target="_blank">Table 1 D1</a>. For visualization purposes the images are thresholded at p<0.005.</p

Behavioral effects during conditioning and test phase.

<p>Treatment experience during the conditioning session (<b>A</b>). Pain ratings (mean VAS score ± SEM) indicate a successful manipulation of the treatment experience for both groups with the placebo patch (treatment A). The effect of treatment history on treatment outcome - response to second treatment (<b>B</b>). Pain ratings indicate that the therapeutic effect (mean pain VAS score ± SEM) of the ointment treatment (treatment B) was significantly lower in the negative than in the positive treatment history group. See the difference between groups in gray bars. Error bars indicate standard error of the mean. * = p<0.01.</p

FMRI results.

<p>Areas of brain activation (BOLD responses from fMRI) during test phase (treatment B).</p><p>S I = primary somatosensory cortex, S II = secondary somatosensory cortex, DLPFC = dorsolateral prefrontal cortex, SMA = supplementary motor area, MCC = middle cingulate cortex, PAG = periaqueductal gray, dACC = dorsal anterior cingulate cortex;</p><p>(**) p<0.05 whole brain corrected,</p><p>(*) p<0.05 small volume corrected using respective a-priori region of interest,</p><p>(^†) p<0.001 uncorrected.</p><p>FMRI results.</p