A paradoxical painful sensation can be elicited by the simultaneous application of innocuous warm and cold stimuli to the skin. In the present study, we analyzed the conditions of production of this unique experimental illusion of pain in 52 healthy volunteers (27 men, 25 women). The stimuli were produced by a thermode composed of six bars whose temperature was controlled by Peltier elements. The temperature of alternate (even- and odd-numbered) bars could be controlled independently to produce various patterns of the 'thermal grill'. After measuring the cold and heat pain thresholds, a series of combinations of warm and cold stimuli, whose distance to the thermal pain threshold was at least 4 degrees C, were applied on the palmar surface of the right hand during 30s. After each stimulus, the subjects had to describe and rate their sensations on visual analog scales. Paradoxical painful sensations, mostly described as burning, were reported by all the subjects but three. However, the phenomenon was less frequent in approximately one third of ('low responder') volunteers. The frequency and intensity of such painful sensations were directly related to the magnitude (i.e. 5-25 degrees C) of the difference of the temperature between the warm and cold bars of the grill. The combination of increasingly colder temperature to a given warm temperature induces similar effects as combining increasingly warmer temperature to a given cold temperature. These results suggest that pain can be the result of a simple addition of non-noxious warm and cold signals.
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