rm the control side, as no relevant side differences have been found for QST variables in the same body region. Then a previously established standardized heat pain paradigm with repetitive blocks of suprathreshold heat pain stimuli was applied to the test site. Thereafter, the areas of flare and secondary mechanical hyperalgesia were mapped first to ensure a constant time between thermal stimulation and flare assessment and to avoid further nociceptor activation by test stimuli. Then, all QST modalities were tested again. All Secondary Hyperalgesia by Repetitive Heat Pain Mechanical pain sensitivity for pinprick stimuli and dynamic mechanical allodynia for stroking light touch. Mechanical pain sensitivity was assessed using custom-made weighted pinprick stimuli with fixed stimulus intensities in order to define a stimulus-response function. These punctate stimuli were adequate to excite cutaneous nociceptors. Pain to light touch was tested by light stroking with a cotton wisp, a cotton wool tip fixed to an elastic strip or a soft brush. Each of the seven intensities of pinpricks and of the three intensities of light stroking was applied five times in a randomized sequence, according to the DFNS protocol, in the central and peripheral zone P1 only due to temporal constraints. Mechanical pain sensitivity was calculated as the geometric mean of all pain RGFA-8 manufacturer ratings for pinprick stimuli and allodynia was calculated as the geometric mean of all pain ratings after light touch stimuli. Mapping and quantification 
of secondary hyperalgesia and flare. Mechanical detection of the area of secondary hyperalgesia developing in skin adjacent to the repetitive heat stimulation was assessed using a calibrated von Frey hair that delivers a force of 256 mN. The contact area of the von Frey hair with the skin was of uniform size and blunt shape. Testing started outside the hyperalgesic area moving towards the centre in 5-mm-steps on Secondary Hyperalgesia by Repetitive Heat Pain previously marked lines yielding 12 marks. The subjects were asked to indicate the point when the sensation of pressure/touch changed to a sensation of pain. The location was marked on the skin using a soft felt-tip pen as were those of the flare that developed around the stimulation site. The tagged points on the skin 13679187 target=_blank”>17594192 indicating hyperalgesia and the visible flare were transferred on an acetate sheet before and immediately after the pain paradigm. The sheets were then scanned and the areas of flare and hyperalgesia quantified using a computer-based system. Additionally, in a separate group of 8 subjects we characterized the time course of the heat-induced primary and secondary hyperalgesia immediately after, and at 1, 2, 4, 8, 12, and 24 h after RHP. To this end, we mapped the areas of secondary hyperalgesia and compared the pain ratings to a single force of pinprick of 256 mN in the primary and secondary hyperalgesia areas. Data evaluation and statistics Heat pain thresholds, suprathreshold heat pain ratings, areas of flare and secondary hyperalgesia, and HSAL scores were analysed as raw data. Warm detection thresholds, which are usually not normally distributed were transformed into decadic logarithms in order to achieve secondary normal distribution. Pain ratings to pinprick and to light touch returned a substantial number of zero pain ratings. Thus, a small constant was added to all pain ratings to avoid loss of zero-values, and then the ratings were log-transformed. Group differe