Altered thermal grill response and paradoxical heat sensations after topical capsaicin application

The thermal grill illusion, where interlaced warm and cold bars cause an unusual burning sensation, and paradoxical heat sensations (PHS), where cold is perceived as warm when alternating warm and cold, are examples of a complex integration of thermal sensations. Here, we investigated the effect of sensitization of heat-sensitive neurons on cold and warm integration. We examined thermal thresholds, PHS, and warm, cold, and pain sensations to alternating cold (10°C) and warm (40°C) bars (the thermal grill [TG]) in the primary area (application site) after topical application with capsaicin and vehicle control (ethanol) on the volar forearms in randomized order in 80 healthy participants. As expected, capsaicin induced heat allodynia and hyperalgesia and decreased cold and cold pain sensation. In addition, we found that after capsaicin application, the TG caused less pain and burning than the 40°C bars alone in contrast to the control side where the TG caused more pain and burning, consistent with the thermal grill illusion. In both situations, the pain intensity during the TG correlated inversely with both cold and warm pain thresholds but not with detection thresholds. Paradoxical heat sensation was only seen in 3 participants after control application but in 19 participants after capsaicin. Those with PHS after capsaicin application had higher detection thresholds to both cold and warm than those without PHS, but there was no difference in thermal pain threshold. These results suggest that a complex cross talk among several cold and warm sensitive pathways shapes thermal perception.