Experimental procedure
pain
SESSION, HEAT
Each participant attended five sessions. Session 1 was a training, familiarity, and calibration session. Subjects were trained to use the Sensory Gracely Scale (0–20) (Session 2 was an expectancy manipulation session. At the beginning of the session, all subjects were informed that the aim of this study was to use a neuromodulation tool (tDCS) to investigate the analgesic effects of lidocaine cream and the hyperalgesic effects of capsaicin cream using a neutral cream as a control. We first applied sham tDCS for 20 min, and then applied all three creams to different spots on participants’ right volar forearm. Subjects were told that the creams needed about 20 min to take effect and that the effect will last for more than two hours. In reality, only sham tDCS was applied, and an inert cream was used for all three creams. The cream was a fragrance-free moisturizing lotion dyed three different colors (blue for “Lidocaine”, pink for “Capsaicin”, and white for “Neutral”).After this scripted explanation, 9 unique regions of the subject’s arm were demarcated for each stimulus. We have drawn a 3 × 3 grid comprised of about 2 cm × 2 cm squares on the subject’s right volar forearm, starting the grid at the subject’s elbow crease. The creams were then applied with each cream spread onto a unique set of 3 adjacent squares (i.e., one cream for each row, Using methods similar to a previous study (Session 3 was the first tDCS session. Right before and after tDCS, resting state fMRI data were collected. Session 4 was the second tDCS session with no fMRI scan involved. Session 5 was the third tDCS and placebo/nocebo test session. At the beginning of this session, subjects were told that the Session 2 procedure would be repeated in the MRI scanner. As in Session 2, the three different creams (in reality all one inert cream) were administered to each row of squares, with “Lidocaine” and “Capsaicin” cream administered to the same rows as determined in Session 2. Then, tDCS was applied based on subjects’ randomization. The resting state fMRI data were collected before and after tDCS.After that, calibrated pain was applied during the fMRI scan. Since this session aimed to test the placebo/nocebo effect, we only administered different heat stimuli to the 3 regions in one column of the 9 × 9 grid. Then, subjects were asked to rate their expectancy of both the analgesia effect of Lidocaine cream and the hyperalgesic effect of Capsaicin using a 0–10 scale. After that, we administered the same moderate stimulus to all remaining regions with all 3 creams (At the end of the experiment, subjects were debriefed. We informed them that in this study, only inert cream and sham tDCS (in session 2 or in sham tDCS group) was used, and that we changed the heat pain temperature at session 2. We also emphasized that the experience of this study should not influence their impression of Lidocaine/Capsaicin or their interest in choosing these drugs as a potential therapeutic method.